Patent Application
20230294073
Superficially porous particles (also called pellicular, fused-core, or core-shell particles) were routinely used as chromatographic sorbents in the 1970's. These earlier superficially porous materials had thin porous layers, prepared from the adsorption of silica sols to the surface of ill-defined, polydisperse, nonporous silica cores (>20 μm). The process of spray coating or passing a solution of sols through a bed of particles was commonly used. Kirkland extensively explored the use of superficially porous particles throughout this time and helped develop the Zipax brand of superficially porous materials in the 1970's. A review of Kirkland's career was provided by Unger (Journal of Chromatography A, 1060 (2004) 1).
Superficially porous particles have been a very active area of research in the past five years. One prior report that uses a mixed condensation of a tetraalkoxysilane with an organosilane of the type YSi(OR)3 where Y contains an alkyl or aryl group and R is methoxy or ethoxy, has been reported by Unger for both fully porous (EP 84,979 B1, 1996) and superficially porous particles (Advanced Materials 1998, 10, 1036). These particles do not have sufficient size (1-2 μm) for effective use in UPLC, nor do they contain chromatographically enhanced pore geometry. Narrow distribution superficially porous particles have been reported by Kirkland (US Application 20070189944) using a Layer-by-Layer approach (LBL)—however these particles are not highly spherical. Other surfactant-templated approaches, can result in low yields of narrow distribution, fully porous particles, however these approaches have not been used to prepare monodisperse, spherical superficially porous particles having chromatographically enhanced pore geometry.
Modern, commercially available superficially porous particles use smaller (<2 μm), monodisperse, spherical, high purity non-porous silica cores. A porous layer is formed, growing these particles to a final diameter between 1.7-2.7 μm. The thickness of the porous layer and pore diameter are optimized to suit a particular application (e.g., small vs. large molecule separations). In order to remove polyelectrolytes, surfactants, or binders (additional reagents added during the synthesis) and to strengthen the particles for use in HPLC or UPLC applications, these materials are calcined (500-1000° C. in air). Additional pore enlargement, acid treatment, rehydroxylation, and bonding steps have been reported.
Evaluation of superficially porous materials (e.g., Journal of Chromatography A, 1217 (2010) 1604-1615; Journal of Chromatography A, 1217 (2010) 1589-1603) indicates improvements in column performance may be achieved using columns packed with these superficially porous materials. While not limited to theory, improvements were noted in van Deemter terms as well as improved thermal conductivity. The University of Cork also has a recent patent application (WO 2010/061367 A2) on superficially porous particles.
Although these reported superficially porous particle processes differ, they can be classified as layering of preformed sols (e.g., AMT process) or growth using high purity tetraalkoxysilane monomers (e.g., the University of Cork process). The AMT and University of Cork processes are similar in that they incorporate a repeated in-process workup (over nine times) using centrifugation followed by redispersion. For the AMT process, this is a requirement of the layer-by-layer approach, in which alternate layers of positively charged poly-electrolyte and negatively charged silica sols are applied. For the University of Cork process, the in-process workup is used to reduce reseeding and agglomeration events. Particles prepared by this approach have smooth particle surfaces and have notable layer formation by FIB/SEM analysis. While both approaches use similar spherical monodisperse silica cores that increase in particle size as the porous layer increases, they differ in final particle morphology of the superficially porous particle. The AMT process, as shown in
The synthesis of narrow particle size distribution porous chromatographic particles is expected to have great benefit for chromatographic separations. Such particles should have an optimal balance of column efficiency and backpressure. While the description of monodisperse superficially porous silica particles has been noted in the literature, these particles do not display chromatographically enhanced pore geometry and desirable pore diameters for many chromatographic applications. Thus, there remains a need for a process in which narrow particle size distribution porous materials can be prepared with desirable pore diameters and chromatographically enhanced pore geometry. Similarly, there remains a need for a process in which narrow particle size distribution porous materials can be prepared with improved chemical stability with high pH mobile phases.
In one aspect, the invention provides a superficially porous material comprising a coated core and one or more layers of a porous shell material surrounding the core, wherein said coated core comprises a substantially nonporous core material coated with a core-coating material.
In another aspect, the invention provides a superficially porous material comprising a substantially nonporous core material coated with a core-coating material and one or more layers of a porous shell material surrounding the coating material.
In certain embodiments, the material of the invention is comprised of superficially porous particles. In other embodiments the material of the invention is comprised of a superficially porous monolith.
In certain embodiments, the material of the invention has a substantially narrow particle size distribution. In particular embodiments the 90/10 ratio of particle sizes of the material is from 1.00-1.55; from 1.00-1.10 or from 1.05-1.10. In specific embodiments, the core has a substantially narrow particle size distribution. In particular embodiments the 90/10 ratio of particle sizes of the core is from 1.00-1.55; from 1.00-1.10 or from 1.05-1.10.
In certain embodiments, the material of the invention has chromatographically enhancing pore geometry.
In other embodiments, the material of the invention has a small population of micropores.
In certain embodiments, the substantially nonporous core material is silica; silica coated with an inorganic/organic hybrid surrounding materia; a magnetic core material; a magnetic core material coated with silica; a high thermal conductivity core material; a high thermal conductivity core material coated with silica; a composite material; an inorganic/organic hybrid surrounding material; a composite material coated with silica; a magnetic core material coated with an inorganic/organic hybrid surrounding material; a high thermal conductivity core material coated with an inorganic/organic hybrid surrounding material; an inorganic core material; or an inorganic core material coated with another inorganic material.
In another aspect of the invention, the said nonporous core is coated with a core-coating material prior to being coated with the shell material. As used herein the term “coated core” is used interchangeably with a “core coated with a core-coating material.”
In another embodiment, the composite material comprises a magnetic additive material or a high thermal conductivity additive or a combination thereof.
In certain embodiments, the core-coating material is an inorganic material, an organic material, or an inorganic/organic hybrid material. In certain embodiments, the porous shell material is a porous silica; a porous composite material; or a porous inorganic/organic hybrid material.
In specific embodiments comprising more than one layer of porous shell material, each layer is independently selected from a porous inorganic/organic hybrid material, a porous silica, a porous composite material or mixtures thereof.
In some embodiments, the substantially nonporous core is a coated core wherein the core material is a composite material and the porous shell material is a porous silica.
In other embodiments, the substantially nonporous core is a coated core wherein the core material is a composite material and the porous shell material is a porous inorganic/organic hybrid material.
In still other embodiments, the substantially nonporous core is a coated core wherein the core material is a composite material and the porous shell material is a composite material.
In yet other embodiments, the substantially nonporous core is a coated core wherein the core material is silica and the porous shell material is a porous composite material.
In certain embodiments, the substantially nonporous core is a coated core wherein the core material is silica and the porous shell material is a porous inorganic/organic hybrid material.
In certain other embodiments, the substantially nonporous core is a coated core wherein the core material is a magnetic core material and the porous shell material is a porous silica.
In still other embodiments, the substantially nonporous core is a coated core wherein the core material is a magnetic core material and the porous shell material is a porous inorganic/organic hybrid material.
In other embodiments, the substantially nonporous core is a coated core wherein the core material is a magnetic core material and the porous shell material is a composite material.
In some embodiments, the substantially nonporous core is a coated core wherein the core material is a high thermal conductivity core material and the porous shell material is a porous silica.
In yet other embodiments, the substantially nonporous core is a coated core wherein the core material is a high thermal conductivity core material and the porous shell material is a porous inorganic/organic hybrid material.
In still other embodiments, the substantially nonporous core is a coated core wherein the core material is a high thermal conductivity core material and the porous shell material is a composite material.
In certain embodiments, the porous inorganic/organic hybrid shell material has the formula:
(SiO2)d/[R2((R)p(R1)qSiOt)m] (I)
wherein,
when 0<p+q≤3; and
when p+q≤2.
In other embodiments, the porous inorganic/organic hybrid shell material has the formula:
(SiO2)d/[(R)p(R1)qSiOt] (I)
wherein,
In yet other embodiments, the porous inorganic/organic hybrid shell material has has the formula:
(SiO2)d/[R2((R1)rSiOt)m] (III)
wherein,
In still other embodiments, the porous inorganic/organic hybrid shell material has the formula:
(A)x(B)y(C)z (IV)
wherein the order of repeat units A, B, and C may be random, block, or a combination of random and block; A is an organic repeat unit which is covalently bonded to one or more repeat units A or B via an organic bond; B is an organosiloxane repeat unit which is bonded to one or more repeat units B or C via an inorganic siloxane bond and which may be further bonded to one or more repeat units A or B via an organic bond; C is an inorganic repeat unit which is bonded to one or more repeat units B or C via an inorganic bond; x and y are positive numbers, and z is a non negative number, wherein x+y+z=1. In certain embodiments, z=0, then 0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.
In other embodiments, the porous inorganic/organic hybrid shell material has the formula:
(A)x(B)y(B*)y*(C)z (V)
wherein the order of repeat units A, B, B*, and C may be random, block, or a combination of random and block; A is an organic repeat unit which is covalently bonded to one or more repeat units A or B via an organic bond; B is an organosiloxane repeat unit which is bonded to one or more repeat units B or B* or C via an inorganic siloxane bond and which may be further bonded to one or more repeat units A or B via an organic bond, B* is an organosiloxane repeat unit which is bonded to one or more repeat units B or B* or C via an inorganic siloxane bond, wherein B* is an organosiloxane repeat unit that does not have reactive (i.e., polymerizable) organic components and may further have a protected functional group that may be deprotected after polymerization; C is an inorganic repeat unit which is bonded to one or more repeat units B or B* or C via an inorganic bond; x, y, and y* are positive numbers and z is a non negative number, wherein x+y+z=1. In certain embodiments, when z=0, then 0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and 0.002≤x/(y+y*+z)≤210.
In certain embodiments, in which the material of the invention comprises more than one layer of porous shell material, each layer is independently selected from is a porous inorganic/organic hybrid material, a porous silica, a porous composite material or mixtures thereof.
In certain embodiments, the core of the material of the invention has an increased hybrid content near the surface of the core.
In other embodiments, the core of the material of the invention has a decreased hybrid content near the surface of the core.
In certain embodiments, the material of the invention has an increased hybrid content near the surface of the superficially porous material.
In other embodiments, the material of the invention has a decreased hybrid content near the surface of the superficially porous material.
In specific embodiments, wherein the material of the invention comprises a composite material, the composite material comprises a magnetic additive material. In some such embodiments, the magnetic additive material has a mass magnetization at room temperature greater than 15 emu/g. In still other embodiments, the magnetic additive material is a ferromagnetic material. In yet other embodiments, the magnetic additive material is a ferrimagnetic material. In specific embodiments the magnetic additive material is a magnetite; maghemite; yttrium iron garnet; cobalt; CrO2; a ferrite containing iron and Al, Mg, Ni, Zn, Mn or Co; or a combination thereof.
In specific embodiments, wherein the material of the invention comprises a magnetic core material, the magnetic core material has a mass magnetization at room temperature greater than 15 emu/g. In still other embodiments, the magnetic core material is a ferromagnetic material. In yet other embodiments, the magnetic core material is a ferrimagnetic material. In specific embodiments the magnetic core material is a magnetite; maghemite; yttrium iron garnet; cobalt; CrO2; a ferrite containing iron and Al, Mg, Ni, Zn, Mn or Co; or a combination thereof.
In specific embodiments, wherein the material of the invention comprises a composite, the composite comprises a high thermal conductive additive material, the composite material comprises a magnetic additive material. In some such embodiments, the high thermal conductivity additive is crystalline or amorphous silicon carbide, aluminum, gold, silver, iron, copper, titanium, niobium, diamond, cerium, carbon, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, or an oxide or a nitride thereof, or combinations thereof. In other embodiments, the high thermal conductivity additive is diamond.
In specific embodiments, wherein the material of the invention comprises a high thermal conductivity core material, the high thermal conductivity core material is crystalline or amorphous silicon carbide, aluminum, gold, silver, iron, copper, titanium, niobium, diamond, cerium, carbon, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, or an oxide or a nitride thereof, or combinations thereof.
In certain embodiments, the material of the invention has a highly spherical core morphology; a rod shaped core morphology; a bent-rod shaped core morphology; a toroid shaped core morphology; or a dumbbell shaped core morphology.
In particular embodiments, the material of the invention has a mixture of highly spherical, rod shaped, bent-rod shaped, toroid shaped or dumbbell shaped core morphologies.
In particular embodiments, the material of the invention has a significantly higher thermal conductivity than a conventional, fully porous silica particle. In other embodiments, the material of the invention has a significantly higher thermal conductivity than a comparable superficially porous silica particle.
In particular embodiments, the material of the invention has a significantly higher thermal conductivity than a fully porous silica particle of the same size. In other embodiments, the material of the invention has a significantly higher thermal conductivity than a superficially porous silica particles of the same size.
In particular embodiments, the material of the invention are capable of forming a packed beds with improved permeability as compared to a conventional, fully porous silica. In still other embodiments, the material of the invention is capable of forming a packed beds with improved permeability as compared to a comparable, superficially porous silica particle.
In particular embodiments, the material of the invention are capable of forming a packed beds with improved permeability as compared to a fully porous silica particles of the same size. In still other embodiments, the material of the invention is capable of forming a packed beds with improved permeability as compared to a superficially porous silica particles of the same size.
In particular embodiments, the material of the invention has improved chemical stability to high pH mobile phases as compared to conventional, unbonded, fully porous silica particles. In still other embodiments, the material of the invention improved chemical stability to high pH mobile phases as compared to comparable, unbonded, superficially porous silica particles.
In particular embodiments, the material of the invention has improved chemical stability to high pH mobile phases as compared to unbonded, fully porous silica particles of the same size. In still other embodiments, the material of the invention improved chemical stability to high pH mobile phases as compared to unbonded, superficially porous silica particles of the same size.
In certain embodiments, the core has a particle size of 0.5-10 μm; 0.8-5.0 μm; or 1.3-3.0 μm.
In other embodiments, each porous layer is independently from 0.05 μm to 5 μm. in thickness as measured perpendicular to the surface of the nonporous core; from 0.06 μm to 1 μm. in thickness as measured perpendicular to the surface of the nonporous core; or from 0.20 μm to 0.70 μm. in thickness as measured perpendicular to the surface of the nonporous core.
In particular embodiments, the materials of the invention have an average particle size between 0.8-20.0 μm; between 1.1-5.0 μm; or between 1.3-2.9 μm.
In other embodiments, the materials of the invention have pores having an average diameter of about 25-600 Å; about 60-350 Å; about 80-300 Å; or about 90-150 Å.
In still other embodiments, the materials of the invention have pores having an average pore volume of about 0.05-1.0 cm3/g; of about 0.09-0.50 cm3/g; of about 0.11-0.45 cm3/g; or of about 0.17-0.30 cm3/g.
In yet other embodiments, the materials of the invention have a surface area is between about 10 m2/g and 600 m2/g; between about 15 m2/g and 300 m2/g; or between about 60 m2/g and 200 m2/g.
In still other embodiments, the materials of the invention are surface modified. In particular embodiments, the materials of the invention are surface modified by:
In certain embodiments of the invention, the superficially porous material has a smooth surface. In other embodiments of the invention, the superficially porous material has a rough surface.
In another aspect, the invention provides a method for preparing a superficially porous material comprising:
In certain embodiments, the method for preparing a superficially porous material further comprises the step of:
In certain aspects, the core-coating material and the nonporous core are composed of different materials. In other aspects the core-coating material and the core are composed of the same materials.
In yet other aspects the core-coating material is composed of a material which enhances one or more of the characteristics selected from the group consisting of chromatographic selectivity, column chemical stability, column efficiency, and mechanical strength. Similarly, in other aspects, the core is composed of a material which enhances one or more characteristics selected from the group consisting of chromatographic selectivity, column chemical stability, column efficiency, and mechanical strength.
In other aspects, the core-coating material is composed of a material which provides a change in hydrophilic/lipophilic balance (HLB), surface charge (e.g., isoelectric point or silanol pKa), and/or surface functionality for enhanced chromatographic separation.
In still other aspects, the core-coating material is independently derived from condensation of one or more polymeric organofunctional metal precursors, and/or polymeric metal oxide precursors on the surface of the core, or application of partially condensed polymeric organofunctional metal precursors, a mixture of two or more polymeric organofunctional metal precursors, or a mixture of one or more polymeric organofunctional metal precursors with a polymeric metal oxide precursor(s) on the surface of the core.
In certain aspects, the core-coating material is an inorganic material, an organic material, or an inorganic/organic hybrid material. In particular embodiments, the core-coating material is an inorganic/organic hybrid material.
In certain aspects, where the core-coating material is inorganic or an inorganic/organic hybrid material, the inorganic portion of the core-coating material is independently selected from the group consisting of alumina, silica, titania, cerium oxide, or zirconium oxides, and ceramic materials. In certain other aspects, the inorganic portion of the core-coating material is aluminum, gold, silver, iron, copper, titanium, niobium, diamond, cerium, carbon, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, or an oxide or a nitride thereof, or combinations thereof.
In still other aspects, the core-coating material is independently derived from condensation of one or more organofunctional silanes and/or tetraalkoxysilane on the surface of the core, or
In some aspects, the coated core may be independently porous or nonporous. Furthermore, the pore structure of the coated core may independently possess or not possess an ordered pore structure. In certain aspects, the coated core may have a chromatographically enhancing pore geometry (CEPG).
In other aspects, the core-coating material may independently comprise from 0-100 mol % hybrid material. In specific aspects, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 0 molar % to not more than about 25 molar %, wherein the pores of the coated core, if present, are substantially disordered. Similarly, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 25 molar % to not more than about 50 molar %, wherein the pores of the coated core, if present, are substantially disordered, and wherein the core-coating material independently possesses a chromatographically enhancing pore geometry (CEPG).
In some aspects, the core-coating material may comprise a material of formula I:
(SiO2)d/[R2((R)p(R1)qSiOt)m]; (1)
wherein,
when 0<p+q≤3; and
when p+q≤2.
yepIn other aspects, the core-coating material may comprise a material of formula II:
(SiO2)d/[(R)p(R1)qSiOt] (II);
wherein,
In still other aspects, the core-coating material may comprise a material of formula III:
(SiO2)d/[R2((R1)rSiOt)m] (III)
wherein,
In yet aspects, the core-coating material may comprise a material of formula IV:
(A)x(B)y(C)z (IV),
wherein the order of repeat units A, B, and C may be random, block, or a combination of random and block;
In still yet other aspects, the core-coating material may comprise a material of formula V:
(A)x(B)y(B*)y*(C)z (V),
wherein the order of repeat units A, B, B*, and C may be random, block, or a combination of random and block;
In certain aspects, the invention provides an inorganic/organic hybrid material wherein the core-coating material is a porous hybrid inorganic/organic material comprising ordered domains have formula IV, V or VI below:
(A)x(B)y(C)z (Formula IV)
(A)x(B)y(B*)y*(C)z (Formula V)
[A]y[B]x (Formula VI),
SiO2/(R4vSiOt)n
In other aspects, the invention provides a coated core which has been surface modified by coating with a polymer. In certain aspects, the coated core has been surface modified with a surface modifier having the formula Za(R′)bSi—R″, where Z═Cl, Br, I, C1-C5 alkoxy, dialkylamino or trifluoromethanesulfonate; a and b are each an integer from 0 to 3 provided that a+b=3; R′ is a C1-C6 straight, cyclic or branched alkyl group, and R″ is a functionalizing group.
In certain aspects, the invention provides an core-coating material further comprising a nanoparticle dispersed within the core-coating material. In other aspects, the nanoparticle may be a mixture of more than one nanoparticle and may be crystalline or amorphous. In still other aspects, the nanoparticle may be silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, oxides thereof, and nitrides thereof.
In another aspect, the invention provides an inorganic/organic hybrid particle comprising a hybrid particle core with an core-coating material wherein said particle has the formula
(Y(CH2)nSiO1.5)x(O1.5SiCH2CH2SiO1.5)y(SiO2)z
In certain aspects, Y is —OH and n is 3. In other aspects, x is 1.0. In still other aspects Y is —OH, n is 3 and x is 1.0. In still other aspects n is from 3 to 12, or from 3 to 8.
In certain embodiments, the substantially nonporous core material is silica, silica coated with an inorganic/organic hybrid surrounding material, magnetic core material, a magnetic core material coated with silica, a high thermal conductivity core material, a high thermal conductivity core material coated with silica, a composite material, a composite material coated with an inorganic/organic hybrid surrounding material, a composite material coated with silica, a magnetic core material coated with an inorganic/organic hybrid surrounding material, a high thermal conductivity core material coated with an inorganic/organic hybrid surrounding material, an inorganic core material, or an inorganic core material coated with another inorganic material.
In other embodiments, each layer of porous shell material wherein each layer is independently selected from a porous inorganic/organic hybrid material, a porous silica, a porous composite material or mixtures thereof.
In still other embodiments, each layer of porous shell material is applied using sols, a polyelectrolyte or a chemically degradable polymer, wherein:
In certain embodiments, each layer of porous shell material is applied by formation through an electrostatic or acid/base interaction of an ionizable group comprising the steps of:
In particular embodiments, the prebonding of the substantially nonporous core or sols includes washing with and acid or base, or a charged polyelectrolyte. In other embodiments, the prebonding of the substantially nonporous core or sols includes chemical transformation of an accessible hybrid organic group.
In still other embodiments the accessible hybrid organic group is an aromatic group that can undergo sulfonation, nitration, amination, or chloromethylation followed by oxidation or nucleophillic displacement with amine containing groups to form ionizable groups. In yet other embodiments, the accessible hybrid organic group is an alkene group that can undergo oxidation, cross-metathesis, or polymerization to form ionizable groups. In specific embodiments, the accessible hybrid organic group is an thiol group that can undergo oxidation, radical addition, nucleophillic displacement, or polymerization to form ionizable groups.
In yet other embodiments, the prebonding of the substantially nonporous core or sols includes bonding with an alkoxysilane that has an ionizable group of equation 1,
R(CH2)nSi(Y)3-x(R′)x (equation 1)
In still yet other embodiments, the prebonding of the substantially nonporous core or sols includes bonding with an alkoxysilane that has an ionizable group of equation 2,
A(CH2)nSi(Y)3-x(R′)x (equation 2)
In particular embodiments, each layer of porous shell material is applied using a polyelectrolyte or a chemically degradable polymer.
In other embodiments, the polyelectrolyte or a chemically degradable is removed from the material by chemical extraction, degradation, or thermal treatment at temperatures less than 600° C., or combinations thereof.
In certain embodiments, each layer of porous shell material is applied using alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, comprising the steps of:
In particular embodiments, the alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, are condensed on the substantially nonporous core in a solution comprising ethanol, water, ammonium hydroxide, an ionic surfactant; and a non-ionic surfactant.
In other embodiments, the ionic surfactant is C10-C30N(R)3+X−, where R is methyl, ethyl, propyl, alkyl, fluoroalkyl; X is a halogen, hydroxide, or of the form R′SO3− or R′CO2− where R′ is methyl, ethyl, butyl, propyl, isopropyl, tert-butyl, aryl, tolyl, a haloalkyl or a fluoroalkyl group.
In yet other embodiments, the ionic surfactant is octadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, or dodecyltrimethylammonium chloride.
In particular embodiments, the concentration of ionic surfactant is maintained in the reaction solution between 5-17 mM; or in certain embodiments between 8-14 mM.
In other embodiments, the non-ionic surfactant is a diblock or triblock copolymer. In certain embodiments, the copolymer is (PEO)x(PPO)y(PEO)x,
wherein
In particular embodiments the triblock copolymer is Pluronic® P123, having (PEO)20(PPO)70(PEO)20. In still other embodiments, the alkoxysilanes, organoalkoxysilanes, or combinations thereof, are condensed on the substantially nonporous core in a solution comprising:
In certain embodiments, the alkoxysilane used is selected from the group of tetramethoxsilane or tetraethoxysilane.
In still other embodiments, the organosiloxane is selected from the group of phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane, diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 2-bis(triethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; or 1,3-bis(trimethoxysilylethyl)benzene.
In yet other embodiments, the alkoxysilane used is tetraethoxysilane and the organoalkoxysilane used is 1,2-bis(triethoxysilyl)ethane.
In certain other embodiments, the concentration of octadecyltrimethylammonium bromide is maintained between 8-14 mM.
In certain other embodiments, the molar ratio of octadecyltrimethylammonium bromide and Pluronic® P123 is maintained at or above 1.30.
In still other embodiments, the molar ratio of alkoxysilane to organoalkoxysilane ranges between 30:1 to 1:30.
In certain embodiments, alkoxysilane, organoalkoxysilane, or combinations thereof are prediluted in ethanol. In certain such embodiments, prediluted ethanol solutions of alkoxysilane, organoalkoxysilane, or combinations thereof are added at a slow and constant rate to prevent fines generation, aggregation and agglomeration. In other such embodiments, prediluted ethanol solutions of alkoxysilane, organoalkoxysilane, or combinations thereof are added a rate between 5-500 μL/min.
In other embodiments, a secondary solution comprising ethanol, water, ammonium hydroxide, ionic surfactant and non-ionic surfactant is added at a slow and constant rate to prevent fines generation, aggregation and agglomeration. In certain such embodiments the secondary solution comprising ethanol, water, ammonium hydroxide, ionic surfactant and non-ionic surfactant is added within a range between the rate required to maintain a uniform ratio of particle surface area (m2) to reaction volume, to the rate required to maintain a uniform ratio of particle volume (m3) to reaction volume.
In certain embodiments, the surfactant mixture is removed through one or more of the following; extractions with acid, water, or organic solvent; ozonolysis treatments, thermal treatments<600° C., or thermal treatments between 500-1300° C.
In still other embodiments, the surfactant mixture is removed through combination of acid extractions and ozonolysis treatments.
In certain embodiments, each layer of porous shell material is applied using alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof: comprising the steps of:
In some such embodiments, the alkoxysilane used is selected from the group of tetramethoxsilane or tetraethoxysilane.
In other such embodiments, the organosiloxane is selected as one or more of the following from the group of phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane, diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; or 1,3-bis(trimethoxysilylethyl)benzene, octadecyltrimethoxysilane, octadecyltriethoxysilane, octyltrimethoxysilane, octyltriethoxysilane, dodecyltrimethoxysilane, and dodecyltriethoxysilane.
In still other such embodiments, the alkoxysilane used is tetraethoxysilane and the organoalkoxysilane used is octadecyltrimethoxysilane.
In certain such embodiments, the alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are prediluted in ethanol.
In some such embodiments, the prediluted ethanol solutions of alkoxysilane, one or more organoalkoxysilanse, or combinations thereof are added a slow and constant rate to prevent fines generation, aggregation and agglomeration.
In other such embodiments, prediluted ethanol solutions of alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are added a rate between 5-500 μL/min.
In certain embodiments, a secondary solution comprising ethanol, water, and ammonium hydroxide is added at a slow and constant rate to prevent fines generation, aggregation and agglomeration.
In certain other embodiments, a secondary solution comprising ethanol, water, and ammonium hydroxide is added within a range between the rate required to maintain a uniform ratio of particle surface area (m2) to reaction volume, to the rate required to maintain a uniform ratio of particle volume (m3) to reaction volume.
In certain embodiments, porosity is introduced through extraction, degradation, hydrolysis, deprotection, or transformation of the hybrid group through one or more of the following; extractions with acid, water, or organic solvent; ozonolysis treatments, thermal treatments<600° C., or thermal treatments between 500-1300° C.
In still other embodiments, porosity is introduced through extraction, degradation, hydrolysis, deprotection, or transformation of the hybrid group through combination of acid extractions, ozonolysis treatments and/or thermal treatments<600° C.
In certain embodiments, each layer is applied using a mixture of formula XX.
(D)d(E)e(F)f (Formula XX)
wherein,
In certain such embodiments, the precursor for the inorganic component upon initial condensation (D) is selected from oxide, hydroxide, ethoxide, methoxide, propoxide, isopropoxide, butoxide, sec-butoxide, tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide, 2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate, nitrate, chlorides, and mixtures thereof of silicon, titanium, zirconium, or aluminum.
In other such embodiments, the precursor for the inorganic component upon initial condensation (D) is selected from tetraethoxysilane, tetramethoxysilane, methyl titanium triisopropoxide, methyl titanium triphenoxide, titanium allylacetoacetatetriisopropoxide, titanium methacrylate triisopropoxide, titanium methacryloxyethylacetoacetate triisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide, pentamethylcyclopentadienyl titanium trichloride, and zirconium methacryloxyethylacetoacetate tri-n-propoxide.
In still other such embodiments, the precursor for the hybrid component upon initial condensation (E) is selected from 1,2-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane, 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane.
In yet other such embodiments, the precursor for the hybrid component upon initial condensation that can be further reacted to increase the porosity of the superficially porous layer (F) is selected from phenyltrimethoxysilane, phenyltriethoxysilane, acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane; chloroethyltriethoxysilane; chloroethyltrimethoxysilane; methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane; bromoethyltrimethoxysilane; bromoethyltriethoxysilane; fluorotriethoxysilane; fluorotrimethoxysilane; and alkoxysilanes of the type:
(CH3CH2O)4-vSi(OR*)v (Formula XXb)
wherein
In such embodiments, porosity is introduced by reaction of hybrid group F through protodesilylation, hydrolysis, deprotection, acid extraction, thermal treatment<500° C., oxidation, ozonolysis or decomposition.
In certain embodiments of the invention, the methods provide materials in which 1-50 layers are formed in the process. In other aspects, 2-30 layers are formed. In still other aspects, 1-5 layers are formed. In yet other aspects, 1-2 layers are formed.
In certain embodiments of the invention the superficially porous material is optimized by acid extraction, classification, ozonolysis treatment, hydrothermal treatment, acid treatment or combinations thereof.
In yet other embodiments of the invention, the superficially porous material is further surface modified. In some aspects by: coating with a polymer; coating with a polymer by a combination of organic group and silanol group modification; a combination of organic group modification and coating with a polymer; a combination of silanol group modification and coating with a polymer; formation of an organic covalent bond between the material's organic group and a modifying reagent; or a combination of organic group modification, silanol group modification and coating with a polymer.
In another aspect, the invention provides a method for increasing the porosity of a substantially nonporous material comprising:
In another aspect, the invention provides a separations device having a stationary phase comprising the superficially porous material of the invention. In certain embodiments, said device is selected from the group consisting of chromatographic columns, thin layer plates, filtration membranes, microfluidic separation devices, sample cleanup devices, solid supports, solid phase extraction devices, microchip separation devices, and microtiter plates.
In certain other embodiments, the separations device is useful for applications selected from the group consisting of solid phase extraction, high pressure liquid chromatography, ultra high pressure liquid chromatography, combinatorial chemistry, synthesis, biological assays, ultra performance liquid chromatography, ultra fast liquid chromatography, ultra high pressure liquid chromatography, supercritical fluid chromatography, and mass spectrometry. In still other embodiments, the separations device is useful for biological assays and wherein the biological assays are affinity assays or ion-exchanged assays.
In another aspect, the invention provides a chromatographic column, comprising
In another aspect, the invention provides a chromatographic device, comprising
In another aspect, the invention provides a kit comprising the superficially porous material of the invention, and instructions for use. In certain embodiments, the instructions are for use with a separations device. In certain other embodiments, the separations device is selected from the group consisting of chromatographic columns, thin layer plates, microfluidic separation devices, solid phase extraction devices, filtration membranes, sample cleanup devices and microtiter plates.
The present invention provides novel chromatographic materials, e.g., for chromatographic separations, processes for its preparation and separations devices containing the chromatographic material. The present invention will be more fully illustrated by reference to the definitions set forth below.
The present invention provides novel chromatographic materials, e.g., for chromatographic separations, processes for its preparation and separations devices containing the chromatographic material. The present invention will be more fully illustrated by reference to the definitions set forth below.
“Hybrid”, including “hybrid inorganic/organic material,” includes inorganic-based structures wherein an organic functionality is integral to both the internal or “skeletal” inorganic structure as well as the hybrid material surface. The inorganic portion of the hybrid material may be, e.g., alumina, silica, titanium, cerium, or “Hybrid” includes inorganic-based structures wherein an organic functionality is integral to both the internal or “skeletal” inorganic structure as well as the hybrid material surface. The inorganic portion of the hybrid material may be, e.g., alumina, silica, titanium, cerium, or zirconium oxides, or ceramic material; in an advantageous embodiment, the inorganic portion of the hybrid material is silica. As noted above, exemplary hybrid materials are shown in U.S. Pat. Nos. 4,017,528, 6,528,167, 6,686,035 and 7,175,913 and International Application Publication No. WO2008/103423.
The term “alicyclic group” includes closed ring structures of three or more carbon atoms. Alicyclic groups include cycloparaffins or naphthenes which are saturated cyclic hydrocarbons, cycloolefins, which are unsaturated with two or more double bonds, and cycloacetylenes which have a triple bond. They do not include aromatic groups. Examples of cycloparaffins include cyclopropane, cyclohexane and cyclopentane. Examples of cycloolefins include cyclopentadiene and cyclooctatetraene. Alicyclic groups also include fused ring structures and substituted alicyclic groups such as alkyl substituted alicyclic groups. In the instance of the alicyclics such substituents can further comprise a lower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF3, —CN, or the like.
The term “aliphatic group” includes organic compounds characterized by straight or branched chains, typically having between 1 and 22 carbon atoms. Aliphatic groups include alkyl groups, alkenyl groups and alkynyl groups. In complex structures, the chains can be branched or cross-linked. Alkyl groups include saturated hydrocarbons having one or more carbon atoms, including straight-chain alkyl groups and branched-chain alkyl groups. Such hydrocarbon moieties may be substituted on one or more carbons with, for example, a halogen, a hydroxyl, a thiol, an amino, an alkoxy, an alkylcarboxy, an alkylthio, or a nitro group. Unless the number of carbons is otherwise specified, “lower aliphatic” as used herein means an aliphatic group, as defined above (e.g., lower alkyl, lower alkenyl, lower alkynyl), but having from one to six carbon atoms. Representative of such lower aliphatic groups, e.g., lower alkyl groups, are methyl, ethyl, n-propyl, isopropyl, 2-chloropropyl, n-butyl, sec-butyl, 2-aminobutyl, isobutyl, tert-butyl, 3-thiopentyl and the like. As used herein, the term “nitro” means —NO2; the term “halogen” designates —F, —Cl, —Br or —I; the term “thiol” means SH; and the term “hydroxyl” means —OH. Thus, the term “alkylamino” as used herein means an alkyl group, as defined above, having an amino group attached thereto. Suitable alkylamino groups include groups having 1 to about 12 carbon atoms, advantageously from 1 to about 6 carbon atoms. The term “alkylthio” refers to an alkyl group, as defined above, having a sulfhydryl group attached thereto. Suitable alkylthio groups include groups having 1 to about 12 carbon atoms, advantageously from 1 to about 6 carbon atoms. The term “alkylcarboxyl” as used herein means an alkyl group, as defined above, having a carboxyl group attached thereto. The term “alkoxy” as used herein means an alkyl group, as defined above, having an oxygen atom attached thereto. Representative alkoxy groups include groups having 1 to about 12 carbon atoms, advantageously 1 to about 6 carbon atoms, e.g., methoxy, ethoxy, propoxy, tert-butoxy and the like. The terms “alkenyl” and “alkynyl” refer to unsaturated aliphatic groups analogous to alkyls, but which contain at least one double or triple bond respectively. Suitable alkenyl and alkynyl groups include groups having 2 to about 12 carbon atoms, advantageously from 1 to about 6 carbon atoms.
The term “alkyl” includes saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups and cycloalkyl substituted alkyl groups. In certain embodiments, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone, e.g., C1-C30 for straight chain or C3-C30 for branched chain. In certain embodiments, a straight chain or branched chain alkyl has 20 or fewer carbon atoms in its backbone, e.g., C1-C20 for straight chain or C3-C20 for branched chain, and more advantageously 18 or fewer. Likewise, advantageous cycloalkyls have from 4-10 carbon atoms in their ring structure and more advantageously have 4-7 carbon atoms in the ring structure. The term “lower alkyl” refers to alkyl groups having from 1 to 6 carbons in the chain and to cycloalkyls having from 3 to 6 carbons in the ring structure.
Moreover, the term “alkyl” (including “lower alkyl”) as used throughout the specification and Claims includes both “unsubstituted alkyls” and “substituted alkyls”, the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfate, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. Cycloalkyls can be further substituted, e.g., with the substituents described above. An “aralkyl” moiety is an alkyl substituted with an aryl, e.g., having 1 to 3 separate or fused rings and from 6 to about 18 carbon ring atoms, e.g., phenylmethyl (benzyl).
The term “amino,” as used herein, refers to an unsubstituted or substituted moiety of the formula —NRaRb, in which Ra and Rb are each independently hydrogen, alkyl, aryl, or heterocyclyl, or Ra and Rb, taken together with the nitrogen atom to which they are attached, form a cyclic moiety having from 3 to 8 atoms in the ring. Thus, the term “amino” includes cyclic amino moieties such as piperidinyl or pyrrolidinyl groups, unless otherwise stated. An “amino-substituted amino group” refers to an amino group in which at least one of Ra and Rb, is further substituted with an amino group.
The term “aromatic group” includes unsaturated cyclic hydrocarbons containing one or more rings. Aromatic groups include 5- and 6-membered single-ring groups which may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine and the like. The aromatic ring may be substituted at one or more ring positions with, for example, a halogen, a lower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF3, —CN, or the like.
The term “aryl” includes 5- and 6-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, unsubstituted or substituted benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine and the like. Aryl groups also include polycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl and the like. The aromatic ring can be substituted at one or more ring positions with such substituents, e.g., as described above for alkyl groups. Suitable aryl groups include unsubstituted and substituted phenyl groups. The term “aryloxy” as used herein means an aryl group, as defined above, having an oxygen atom attached thereto. The term “aralkoxy” as used herein means an aralkyl group, as defined above, having an oxygen atom attached thereto. Suitable aralkoxy groups have 1 to 3 separate or fused rings and from 6 to about 18 carbon ring atoms, e.g., O-benzyl.
The term “ceramic precursor”” is intended include any compound that results in the formation of a ceramic material.
The term “chiral moiety” is intended to include any functionality that allows for chiral or stereoselective syntheses. Chiral moieties include, but are not limited to, substituent groups having at least one chiral center, natural and unnatural amino-acids, peptides and proteins, derivatized cellulose, macrocyclic antibiotics, cyclodextrins, crown ethers, and metal complexes.
The language “chromatographically-enhancing pore geometry” includes the geometry of the pore configuration of the presently-disclosed materials, which has been found to enhance the chromatographic separation ability of the material, e.g., as distinguished from other chromatographic media in the art. For example, a geometry can be formed, selected or constructed, and various properties and/or factors can be used to determine whether the chromatographic separations ability of the material has been “enhanced”, e.g., as compared to a geometry known or conventionally used in the art. Examples of these factors include high separation efficiency, longer column life and high mass transfer properties (as evidenced by, e.g., reduced band spreading and good peak shape.) These properties can be measured or observed using art-recognized techniques. For example, the chromatographically-enhancing pore geometry of the present porous materials is distinguished from the prior art particles by the absence of “ink bottle” or “shell shaped” pore geometry or morphology, both of which are undesirable because they, e.g., reduce mass transfer rates, leading to lower efficiencies. Chromatographically-enhancing pore geometry is found in porous materials containing only a small population of micropores. Porous materials with such a low micropore surface area (MSA) give chromatographic enhancements including high separation efficiency and good mass transfer properties (as evidenced by, e.g., reduced band spreading and good peak shape). Micropore surface area (MSA) is defined as the surface area in pores with diameters less than or equal to 34A, determined by multipoint nitrogen sorption analysis from the adsorption leg of the isotherm using the BJH method. As used herein, the acronyms “MSA” and “MPA” are used interchangeably to denote “micropore surface area”.
The term “functionalizing group” includes organic functional groups which impart a certain chromatographic functionality to a chromatographic stationary phase.
The term “heterocyclic group” includes closed ring structures in which one or more of the atoms in the ring is an element other than carbon, for example, nitrogen, sulfur, or oxygen. Heterocyclic groups can be saturated or unsaturated and heterocyclic groups such as pyrrole and furan can have aromatic character. They include fused ring structures such as quinoline and isoquinoline. Other examples of heterocyclic groups include pyridine and purine. Heterocyclic groups can also be substituted at one or more constituent atoms with, for example, a halogen, a lower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF3, —CN, or the like. Suitable heteroaromatic and heteroalicyclic groups generally will have 1 to 3 separate or fused rings with 3 to about 8 members per ring and one or more N, O or S atoms, e.g. coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolidinyl.
The term “metal oxide precursor” is intended include any compound that contains a metal and results in the formation of a metal oxide, e.g., alumina, silica, titanium oxide, zirconium oxide, or cerium oxide.
The term “monolith” is intended to include a collection of individual particles packed into a bed formation, in which the shape and morphology of the individual particles are maintained. The particles are advantageously packed using a material that binds the particles together. Any number of binding materials that are well known in the art can be used such as, for example, linear or cross-linked polymers of divinylbenzene, methacrylate, urethanes, alkenes, alkynes, amines, amides, isocyanates, or epoxy groups, as well as condensation reactions of organoalkoxysilanes, tetraalkoxysilanes, polyorganoalkoxysiloxanes, polyethoxysiloxanes, and ceramic precursors. In certain embodiments, the term “monolith” also includes hybrid monoliths made by other methods, such as hybrid monoliths detailed in U.S. Pat. No. 7,250,214; hybrid monoliths prepared from the condensation of one or more monomers that contain 0-99 mole percent silica (e.g., SiO2); hybrid monoliths prepared from coalesced porous inorganic/organic particles; hybrid monoliths that have a chromatographically-enhancing pore geometry; hybrid monoliths that do not have a chromatographically-enhancing pore geometry; hybrid monoliths that have ordered pore structure; hybrid monoliths that have non-periodic pore structure; hybrid monoliths that have non-crystalline or amorphous molecular ordering; hybrid monoliths that have crystalline domains or regions; hybrid monoliths with a variety of different macropore and mesopore properties; and hybrid monoliths in a variety of different aspect ratios. In certain embodiments, the term “monolith” also includes inorganic monoliths, such as those described in G. Guiochon/J. Chromatogr. A 1168 (2007) 101-168.
The term “nanoparticle” is a microscopic particle/grain or microscopic member of a powder/nanopowder with at least one dimension less than about 100 m, e.g., a diameter or particle thickness of less than about 100 nm (0.1 mm), which may be crystalline or noncrystalline. Nanoparticles have properties different from, and often superior to those of conventional bulk materials including, for example, greater strength, hardness, ductility, sinterability, and greater reactivity among others. Considerable scientific study continues to be devoted to determining the properties of nanomaterials, small amounts of which have been synthesized (mainly as nano-size powders) by a number of processes including colloidal precipitation, mechanical grinding, and gas-phase nucleation and growth. Extensive reviews have documented recent developments in nano-phase materials, and are incorporated herein by reference thereto: Gleiter, H. (1989) “Nano-crystalline materials,” Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis and properties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. In certain embodiments, the nanoparticles comprise oxides or nitrides of the following: silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In certain embodiments, the nanoparticles of the present invention are selected from diamonds, zirconium oxide (amorphous, monoclinic, tetragonal and cubic forms), titanium oxide (amorphous, anatase, brookite and rutile forms), aluminum (amorphous, alpha, and gamma forms), and boronitride (cubic form). In particular embodiments, the nanoparticles of the present invention are selected from nano-diamonds, silicon carbide, titanium dioxide (anatase form), cubic-boronitride, and any combination thereof. Moreover, in particular embodiments, the nanoparticles may be crystalline or amorphous. In particular embodiments, the nanoparticles are less than or equal to 100 nm in diameter, e.g., less than or equal to 50 nm in diameter, e.g., less than or equal to 20 nm in diameter.
The term “substantially disordered” refers to a lack of pore ordering based on x-ray powder diffraction analysis. Specifically, “substantially disordered” is defined by the lack of a peak at a diffraction angle that corresponds to a d value (or d-spacing) of at least 1 nm in an x-ray diffraction pattern.
“Surface modifiers” include (typically) organic functional groups which impart a certain chromatographic functionality to a chromatographic stationary phase. The porous inorganic/organic hybrid particles possess both organic groups and silanol groups which may additionally be substituted or derivatized with a surface modifier.
The language “surface modified” is used herein to describe the composite material of the present invention that possess both organic groups and silanol groups which may additionally be substituted or derivatized with a surface modifier. “Surface modifiers” include (typically) organic functional groups which impart a certain chromatographic functionality to a chromatographic stationary phase. Surface modifiers such as disclosed herein are attached to the base material, e.g., via derivatization or coating and later crosslinking, imparting the chemical character of the surface modifier to the base material. In one embodiment, the organic groups of a hybrid material, e.g., particle, react to form an organic covalent bond with a surface modifier. The modifiers can form an organic covalent bond to the material's organic group via number of mechanisms well known in organic and polymer chemistry including but not limited to nucleophilic, electrophilic, cycloaddition, free-radical, carbene, nitrene, and carbocation reactions. Organic covalent bonds are defined to involve the formation of a covalent bond between the common elements of organic chemistry including but not limited to hydrogen, boron, carbon, nitrogen, oxygen, silicon, phosphorus, sulfur, and the halogens. In addition, carbon-silicon and carbon-oxygen-silicon bonds are defined as organic covalent bonds, whereas silicon-oxygen-silicon bonds that are not defined as organic covalent bonds. A variety of synthetic transformations are well known in the literature, see, e.g., March, J. Advanced Organic Chemistry, 3rd Edition, Wiley, New York, 1985.
The language, “composite material” and the term “composite” are used interchangeably herein to describe the engineered materials of the invention composed of one or more components described herein in combination with dispersed nanoparticles, wherein each component/nanoparticle remains separate and distinct on a macroscopic level within the finished structure. The composite material of the present invention is independent of form, and may be monolithic or particulate in nature. Moreover, a short-hand convention may be used to describe a composite material containing a dispersed nanoparticle, Np/(A)w(B)x(C)y, and may be understood as follows: the symbolic representation to the left of the slash mark represents the dispersed nanoparticle, and the symbolic representations to the right of the slash mark represent the components that comprise the material that the nanoparticle (noted on the left of the slash mark) is dispersed within. In certain embodiments, the composite materials of the present invention may be nanocomposites, which are known to include, at least, for example, nano/nano-type, intra-type, inter-type, and intra/inter-type. (Nanocomposites Science and Technology, edited by P. M. Ajayan, L. S. Schadler, P. V. Braun, Wiley-VCH (Weinheim, Germany), 2003)
The terms “material having a high thermal conductivity”, “high thermal conductivity core”, and a “high thermal conductivity additive” are defined as a material, core material, or composite additive having a thermal conductivity greater than 20 W/(m·K). In various embodiments the additive has a thermal conductivity ranges from: about 20 W/(m·K) to not more than 3500 W/(m·K); about 100 W/(m·K) to not more than 3300 W/(m·K); and 400 W/(m·K) to not more than 3000 W/(m·K). High thermal conductivity cores or additives can be, for example and without limitation, a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity core or additive includes (but is not limited to) aluminum, gold, silver, iron, copper, titanium, niobium, diamond, cerium, carbon, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, or an oxide or a nitride thereof, or combinations thereof.
A “high thermal diffusivity” core or additive is defined as an additive used in a superficially porous materials as having a thermal diffusivity greater than 20 mm2/s. In various embodiments the core or additive has a thermal diffusivity ranges from: about 20 mm2/s to not more than 2000 mm2/s; about 100 mm2/s to not more than 1600 mm2/s; and 150 mm2/s to not more than 1400 mm2/s. This high thermal conductivity core or additive can be a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity core or additive includes (but is not limited to) aluminum, copper, gold, and diamonds.
A “high thermal conductivity superficially porous material (or particle)” is defined as a material that has improved thermal conductivity or improved thermal diffusivity over a comparable porous silica particle, particularly of the same size. In various embodiments the higher thermal conductivity superficially porous material is a material that has improved thermal conductivity or thermal diffusivity over a comparable superficially porous silica particle, particularly of the same size. In various embodiments the higher thermal conductivity superficially porous material is a material that has improved thermal conductivity over a comparable fully porous hybrid particle, particularly of the same size. Determination of particle thermal conductivity can be made by the method of Gritti and Guiochon [J. Chromatogr. A, 2010, 1217, 5137) taking into account differences in bulk material properties, pore volume, surface modification type and coverage.
7S] The terms “magnetic material”, “magnetic cores” and “magnetic additives” are defined as a material, core material, or composite additive that gas a mass magnetization (a, magnetic moment per unit mass, magnetic saturation or saturation magnetization) at room temperature greater than 15 emu/g (A m2/kg). This includes ferromagnetic and ferrimagnetic materials, including (but is not limited to): magnetite (ferrous ferric oxide); maghemite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co). Magnetic core particles do not include other oxides of iron, including hematite and goethite, that have mass magnetization values less than 10 emu/g. Hematite (0.4 emu/g) is considered antiferromagnetic at room temperature.
As used herein, the term “fines” refers to undesired materials generated in the processes of the invention that are below the 10 vo % of the target particle size distribution. Fines can be formed from reseeding events or from particle breakage. Resulting fines can be nonporous or fully porous. Often fines are substantially smaller than the 10 vol % of the target particle size distribution. Often fines are <1 um in size. Very small fines can cause problems in chromatography in that the percolate through the packed bed and get stuck in the outlet frit. This generates increased column pressure. Alternatively fines small enough to percolate through the packed bed and outlet frit can result in problems with detectors and can contaminate a product. Problems with detector include clogging flow channels, blocking detector windows, and anomalous detector readings. Such issues can reduce the lifetime of a detector and can require extensive cleaning protocols. Such issues can also impact the precision, accuracy, reliability, reproducibility, and robustness of analytical data generated. Fines can be removed by classification.
As used herein, the terms “aggregates” and “agglomerates” refer to undesired materials generated in the processes of the invention that are larger than the 90 vol % of the target particle size distribution. aggregates and/or agglomerates can form from imperfections of the core material, improper mixing or dispersion in the process, or excessive forces during workup. Aggregates and agglomerates can impact the efficiency, permeability, reproducibility and robustness of packed beds within chromatographic columns. It is difficult to optimally pack a chromatographic column with materials having an elevated amount of aggregates and agglomerates. Aggregates and agglomerates can break apart within a packed bed structure when exposed to high pressures and shears. This can result in a mechanical instability of the packed bed and the result of a void on the top of the column. This breaking of aggregates and agglomerates can also result in the generation of fines. Aggregates and agglomerates can be removed by classification.
As used herein, the term “small population of micropores” refers to is defined as having less than or equal to 40 m2/g of the surface area resides in pores less than or equal to 34 Å—as determined by t-plot
As used herein, the term “high pH stability,” also referred to as “base stability”, is measured by significant changes, or lack thereof, in column performance or attributes, such as efficiency, peak capacity, peak shape, retention factor, column pressure, column hold-up volume, or stationary phase mass, due to exposure to high pH mobile phase (pH>7) over an extended period of time generally acceptable to one skilled in the art. This period of time is highly dependent on pH, temperature, mobile phase type, and column volumes. Typical testing mobile phases are in the pH range of 7-12, more specifically 8-11, and include, but are not limited to, the following: Ammonium Hydroxide, Sodium Hydroxide, Triethylamine, Ammonium Bicarbonate, Diethylamine, Pyrrolidin, Ammonium Formate, Ammolnium acetate, Ammonium chloride, Triethylammonium bicarbonate, Dimethylhexyl amine, Tris(2-aminoethyl)amine. Typical testing temperatures are 0-100° C., more specifically, 10-90° C., more specifically 20-80° C., more specifically 25-75° C., more specifically 30-70° C. Materials are not considered “high pH stable” or “base stable” if one or more of the following changes in performance or attributes are observed: Losing more than 30% of initial efficiency or more than 15% of initial peak capacity and/or, a significant shift in peak shape denoted by a peak tailing factor (USP tailing factor)<0.90, indicating severe “peak fronting” and/or, column pressure increase of more than 15% over the initial pressure and/or, losing more than 30% of initial retention factor and/or, increasing column hold-up more than 10% and/or, losing more than 20-40% of the stationary phase mass [being swept out of the column by the mobile phase] and/or, generally failing to provide acceptable separation after exposure to high pH mobile phase.
As used herein, the term “substantially nonporous” refers to a material which, although porous, is impermeable or otherwise functions as a nonporous material. Such a substantially nonporous material has a pore volume of less than about 0.10 cc/g. In certain embodiments, the term “substantially nonporous” may refer to a fully nonporous material.
As used herein the term “90/10 ratio” refers to the ratio of the particle size distribution of a particulate material of the invention. In the 90/10 ratio, the particle sizes of the material is measured and plotted on an S-curve. The particle size value of represented by 90% of the particles (i.e. the value for which 90% of the particles are equal to or smaller than) is compared as a ratio to the particle size value represented by 10% of the particles (i.e., the value for which 10% of the particles is equal to or smaller than) Hybrid Inorganic/Organic Superficially Porous Particles.
Hybrid particle technologies are highly desirable for many chromatographic applications due to the increased chemical stability and reduced silanol activity they provide. One key advantage of hybrid particles over silica particles in chromatographic applications is their superior column stability when used with alkaline mobile phases (pH 8-12). Silica packing materials have limited lifetimes under these conditions due to the dissolution of the silica and collapse of the packed bed.
Approaches to the synthesis of hybrid superficially porous particles with a coated core.
In one approach spherical silica or hybrid non-porous cores are prepared following standard protocols. A coating material is applied to the core using the processes described herein. After preparation of the coated core, a superficially porous layer is formed using two or more of the following; TEOS, a thermally degradable organofunctional silane (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane) along with more thermally stable hybrid silanes, such as (but not limited to) phenylene bridged silanes. In this process lower temperature thermal treatment (<600° C.) is performed to degrade the thermally degradable organofunctional silane as a means to introduce porosity, while maintaining the more thermally stable hybrid group. Thermal treatment<550° C., <640° C., or <500° C., may also be used. The temperature is determined by TGA experiments performed in air. Additional steps of classification, pore modification, acid treatment and bonding are performed, as detailed herein.
In another approach, spherical hybrid non-porous cores are prepared following standard protocols. A coating material is applied to the core using the processes described herein. After preparation of the coated core, a superficially porous layer is prepared using a surfactant or a mixed surfactant approach using one or more silanes that include (but is not limited to) TEOS, a lower temperature degradable organofunctional silane (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), ethylene bridged alkoxysilanes, or phenylene bridged alkoxysilanes. The surfactant is removed using an acid ethanol process (e.g., hydrochloric acid in ethanol). Alternatively, the surfactant is removed by thermal treatment (<600° C.) at a temperature that preserves the hybrid group, while removing the surfactant. This temperature is determined by TGA experiments performed in air. Thermal treatment<550° C., <640° C., or <500° C., may also be used. Alternatively the surfactant is removed by oxidation (e.g., ozonolysis). Alternatively, one or more of the surfactants used in this process are selected from the group of acid labile, base labile, or other labile surfactants. These labile surfactants can be reacted and removed later by selecting the correct chemical conditions (e.g., acid hydrolysis, base hydrolysis, reduction or oxidation, hydrogenation or hydrogenolysis). Additional steps of classification, pore modification, acid treatment and bonding are performed, as detailed above.
In another approach, spherical silica or hybrid non-porous cores are prepared following standard protocols. Separately a hybrid sol (<100 nm) solution is prepared using one or more silanes that include (but is not limited to) TEOS, lower temperature degradable organofunctional silane (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), ethylene bridged alkoxysilanes, or phenylene bridged alkoxysilanes. After preparation of the core material, the cores are coated by the processes described herein after which a superficially porous layer is prepared. A uniform superficially porous layer is then prepared in a layer-by-layer approach using a suitable positively charged polyelectrolyte. Suitable polyelectrolytes include (but is not limited to) linear, branched, and block polymers containing one or more of the following groups; alkyl, cycloalkyl, aryl, ethylene oxide groups along with one or more of the following groups; primary, secondary, tertiary and quaternary amino groups, pyrrolidone, pyridine, and imidazole. The polyelectrolyte is removed by thermal treatment (<600° C.) at a temperature that preserves the hybrid group, while removing the polyelectrolyte. Thermal treatment<550° C., <640° C., or <500° C., may also be used. This temperature is determined by TGA experiments performed in air. Alternatively the polyelectrolyte is removed by ozonolysis. Additional steps of classification, pore modification, acid treatment and bonding are performed, as detailed herein.
Recent studies (Gritti, F. Journal of Chromatography A, 1217 (2010) 5069-5083) suggest superficially porous silica particles have significantly higher thermal conductivities when compared to comparable fully porous particles, particularly of the same size. This higher thermal conductivity is one reason why superficially porous particles were noted to have improved chromatographic performance.
Approach to the Synthesis of Higher Thermal Conductivity Superficially Porous Particles
It is well known that many materials have higher thermal conductivities than silica. Included in this is diamond. Micron and sub-micron sized diamond particles are well known, and can be prepared from natural and chemical processes. Alternatively diamond nanoparticles can be incorporated within non-porous cores (including non-porous silica) The use of a diamond core (0.5-3 μm) for a superficially porous particle may result in a measurable increase in thermal conductivity when compared to a silica based superficially porous particle of comparable size. In order to reduce undesired chromatographic interactions that may result from a diamond core, a non-porous silica or hybrid surface coating may be advantageously used. This surface coating step may be advantageously repeated or performed in a growth-process to achieve the desired thickness. Calcination and surface rehydroxylation may be advantageously used at the end of this step.
The superficially porous layer may be silica or hybrid, and can be prepared in any of the processes described herein. Additional steps of classification, calcination, pore modification, re-calcination, rehydroxylation and bonding are then performed (as required), as detailed herein.
The impact of particle attributes on packed bed permeability can be modeled using the Kozeny-Carman equation. One can use this equation to model pressures required to push a solvent through a column packed with particles that varies in interstitial fraction (ε) and particle size (dp). Pressure changes with the square of particle size (based on number count), while column efficiency correlates linearly with particle size (based on volume count). As a result, decreasing particle size to improve efficiency results in a dramatic increase in column pressure. While chromatographic systems exist that can handle increased column pressures, it is desirable to obtain the lowest column pressures available for a given particle size. One means to achieve this is to decrease the difference between the number and volume average particle size. For example, using particles that are monodisperse. Monodisperse non-porous, fully porous and superficially porous particles have been reported. For the latter the ability to prepare monodisperse particles is a function of the non-porous core as well as the uniformity of the porous layer. As described herein, the materials of the instant invention provide improved permeability as well as improved chemical stability with high pH mobile phases.
Approach to the Synthesis of Superficially Porous Particles that Form Packed Beds with Improved Permeability.
A further improvement in permeability can be achieved if the particle shape is modified. For example, a uniform micron-sized doughnut, rod, dumbbell, star, or bent-rod-shaped cores is used in place of a highly spherical core. Additional shapes include (but not limited to) spirals, discoidal, concave disks, spools, rings, helix, saddles, cross, cube, derby, helix, cylinders, and tubes. Examples of dumbbell, doughnut, rod, spiral, and gyroid particles have been reported {Doshi, N. PNAS, 2009, 106, 51, 21495; Alexander, L. Chem. Commun., 2008, 3507; Naik, S. J. Phys. Chem. C 2007, 111, 11168; Pang, X. Microporous and Mesoporous Materials 85 (2005) 1; Kievsky, Y. IEEE Transactions on Nanotechnology, 2005, 4, 5, 490; Sugimoto, T. in Monodispersed Particles, (Elsevier Science BV, Amsterdam) 2001; Ozin, G. Adv. Mater., 1997, 9, 662}.
Important factors for the non-spherical cores is that they be relatively uniform in dimensions, free-flowing, non-porous, and mechanically strong enough for use in HPLC and UPLC. The composition of these cores may be selected from (but is not limited to) silica, metal oxides, diamonds, heavily cross linked polymers, and hybrid materials. Improvements in core uniformity can be achieved through classification. A reduction in porosity can be achieved by pore filling with a similar or different composition (e.g., pore filling a silica material with a crosslinked polymer composition). Improvements in mechanical strength is achieved by increasing crosslinking with the same or different composition (e.g., creating a silica network within a polymer composition), or by calcination. For the latter, higher temperatures (e.g., >800° C.) may be advantageously used.
In addition to the core coating material described herein, and in order to reduce undesired chromatographic interactions due to the core, a non-porous surface coating with a silica, hybrid, or polymeric composition may be advantageously used. This surface coating step may need to be repeated or performed in a growth-process to achieve the desired thickness. To ensure that the core morphology is not substantially modified, this step advantageously provides a uniform surface layer. Calcination and surface rehydroxylation may be advantageously used at the end of this step.
After coating the core with the core coating material as described herein, a uniform silica or hybrid superficially porous layer may be formed from any one of the processes described above. To ensure the core morphology is not substantially modified, this step advantageously yields a highly uniform porous layer. Additional steps of classification, calcination, pore modification, re-calcination, rehydroxylation and bonding are then performed (as required) as detailed above. These non-spherical superficially porous materials can be packed in chromatographic columns individually or as mixtures with other shapes, or with spherical particles. It is important to optimize column packing conditions for these mixed systems. Considerations of maintaining similar dispersion, bulk density and settling rates between the different materials need to be made.
As noted herein, the AMT process and the University of Cork process both require repeated in-process workups using centrifugation followed by redispersion during the formation of the superficially porous layer. The concerns with repeated centrifugation is aggregation/agglomeration, difficulty redispersing particles, product uniformity, and long labor times required for this process. Aggregation and agglomeration are extremely detrimental for this process. It is possible for aggregates/agglomerates to be further coated in both of these processes. By its nature repeated centrifugation allows for these un-aged, ‘green’ materials to get close to each other. Excessive centrifugation time and g-forces can results in a tight bed structure that can be hard to redisperse. Filtration (including tangential filtration) is an alternative to centrifugation that allows for a less compact bed to be formed. Unfortunately the time period required to filter<3 μm materials that may be laden with sub-micron fines is prohibitive. These sub-micron fines can readily clog the filter material preventing complete filtration to occur.
There are also many methods available to redisperse particles, including sonication using sonic baths, in-line sonicators, in-tank sonicators, sonic horns, rotor-stator mixers, milling, low shear and high shear mixing (e.g., saw-tooth impellers). Optimization of amplitude, frequency and pulse sequences is used for optimal sonication. Adjusting the conductivity, pH and surfactant mixture can also be used to optimally redisperse particles (through solvent washes, or controlled order of addition of reagents). One concern for these redispersion methods is the potential to harm the superficially porous layer. It is expected that elevated shears may result in a fracturing of the porous layer. The resulting material may have bare-spots, or non-uniform porous layers.
A further concerns is the long reaction times required for an iterative process, such as those described by AMT and the University of Cork. While such materials can be prepared on a laboratory and batch scale, the times required for these processes can exceed those typically used for the synthesis of fully porous particles.
Another concern for uniform shell processes such is the impact of reseeding. Reseeded particles (<0.5 μm) can emerge during the growth step. If they are not effectively removed, the will start to grow preferentially over the larger porous layer, solid core materials. At some point the two particle distributions can overlap. The end result of this, after further processing steps, is the overlapping mixture of superficially porous and fully porous particles. These overlapping mixture of particles are difficult to separate, quantify or understand the impact on chromatographic performance (including chromatographic reproducibility).
Approach to the Improved Synthesis of Superficially Porous Materials.
In this approach magnetic capture methods are used to collect magnetic core particles in place of centrifugation or filtration. These methods include in-tank, in-line, or off-line magnetic capture.
In-tank magnetic capture uses a removable magnetic rod (or alternatively an electromagnet) placed within a removable or permanent glass sleeve or baffle. In this approach the magnetic rod is placed within the glass sleeve during the time of capture. After the remaining reaction solution is emptied and a new wash or reaction solvent is added, the magnetic rod is removed and bound magnetic core particles are redispersed. Alternatively, an external magnet is placed on the side of the reactor allowing magnetic core particles to be captured on the reactor side-wall. After the remaining reaction solution is emptied and a new wash or reaction solvent is added, the external magnet is removed and bound magnetic core particles are redispersed.
The in-line magnetic capture method involves pumping the reaction solution in a recirculation loop through a collection container. This collection container is placed within a magnetic holding block. Magnetic core particles are collected in this container. After the remaining reaction solution is emptied and a new wash or reaction solvent is added, the collection container is removed from the magnetic holding block and the bound magnetic core particles are redispersed as they are pumped back into the reaction vessel. By using the appropriate sized collection container (advantageously containing one or more flat surfaces) this approach has an advantage in that it allows for good control of the surface area exposed to the magnetic field.
The off-line magnetic capture method is similar to filtration in that the reaction solution is transferred to a secondary vessel. In this secondary vessel, a magnetic field is applied to allow for the controlled collection of magnetic core particles. Reaction solution or wash solvents are removed by filtration, decanting, or by siphon. Magnetic core particles are redispersed in the appropriate solvent and transferred back to the reaction vessel.
During the magnetic capture step for all of these approaches, a loose collection of magnetic core particles is formed. These collections of core particles are less dense than the cake formed by excessive centrifugation. As a result these particles are easier to redisperse. The manner of redispersing magnetic core particles is similar to the approaches described above.
In this approach a non-porous magnetic core is used in place of a non-porous silica or hybrid core. This magnetic core can contain (but is not limited to) magnetic forms of iron oxides, iron, metals, metal oxides, chromium dioxide, ferrites, or cobalt. Advantageously the magnetic core contains magnetite, maghemite. The magnetic core can exist as a pure metal or metal oxide or exist in combination with a second material that includes (but is not limited to) silica, hybrid, polymer, or non-magnetic materials. For example, a magnetic core can be formed by incorporating <100 nm magnetite or cobalt nanoparticles within non-porous silica or polymer particles. The magnetic nanoparticles can be homogeneously dispersed nanoparticles or dispersed clusters of nanoparticles within this material, adsorbed only to the surface, or contained only in the interior of the non-porous core particles. Alternatively 0.3-1.5 μm magnetite or cobalt particles can be used as the non-porous core. Magnetic capture methods are used in this process in place of centrifugation or filtration.
In order to reduce undesired chromatographic interactions due to the core, a non-porous surface coating with a silica, hybrid, or polymeric composition may be advantageously used. This surface coating step may be advantageously repeated or performed in a growth-process to achieve the desired thickness. Magnetic capture methods are used in this process in place of centrifugation or filtration. To ensure that the core morphology is not substantially modified, this step advantageously provides a uniform surface layer. Calcination and surface rehydroxylation may advantageously used at the end of this step.
After coating the core with a core coating material as described herein, a uniform silica or hybrid superficially porous layer may be formed from any one of the processes described above. To ensure the core morphology is not substantially modified, this step advantageously yield a highly uniform porous layer. Magnetic capture methods are used in this process in place of centrifugation or filtration. Additional steps of classification, calcination, pore modification, re-calcination, rehydroxylation and bonding are then performed (as required) as detailed above.
Considering the problem associated with reseeded particles for uniform layer processes such as the novel one described above or the University of Cork process, a magnetic core particle allows for a unique means to separate the porous layer materials from reseeded particles. This can be utilized in-process or during product workup.
The use of magnetic core particles as well as magnetic capture methods allows for a unique process of automating the synthesis of superficially porous particles. The use of in-tank magnetic capture (e.g., using electromagnets) allows for full automation of particle collection. Automated bottom valves and solvent addition valves, are used to fully automate synthesis conditions. In-tank or in-line particle size measurements are used to monitor reaction performance and determined reaction completion.
The invention provides superficially porous materials, particles and/or monoliths comprising a substantially nonporous inorganic/organic core, core-coating material and one or more layers of a porous shell material surrounding the core.
In certain embodiments, the superficially porous material of the invention a substantially narrow particle size distribution. In certain other embodiments, the 90/10 ratio of particle sizes is from 1.00-1.55. In specific embodiments, the 90/10 ratio of particle sizes is from 1.00-1.10 or from 1.05-1.10. In other specific embodiments, the 90/10 ratio of particle sizes is from 1.10-1.55; from 1.10-1.50; or from 1.30-1.45.
In certain embodiments, the superficially porous material of the invention, wherein the material has chromatographically enhancing pore geometry. That is, in some embodiments, the superficially porous material of the invention has only a small population of micropores.
In certain embodiments, the substantially nonporous core material is silica; silica coated with an inorganic/organic hybrid material; a magnetic core material; a magnetic core material coated with silica; an inorganic/organic hybrid core material; an inorganic/organic hybrid core material coated with silica; a high thermal conductivity core material; a high thermal conductivity core material coated with silica; a composite material; an inorganic/organic hybrid surrounding material; a composite material coated with silica; a magnetic core material coated with an inorganic/organic hybrid surrounding material; a high thermal conductivity core material coated with an inorganic/organic hybrid surrounding material; a silica core material coated with a magnetic material; or a silica core material coated with a magnetic material subsequently coated with silica. In certain other embodiments, the core material may be a diamond, graphite, zirconium oxide (amorphous, monoclinic, tetragonal and cubic forms), titanium oxide (amorphous, anatase, brookite and rutile forms), aluminum (amorphous, alpha, and gamma forms), and boronitride (cubic form). In certain other embodiments, the core material may be coated with an inorganic material prior to applying the core-coating material of the invention wherein the inorganic material includes, but is not limited to, diamond, graphite, zirconium oxide (amorphous, monoclinic, tetragonal and cubic forms), titanium oxide (amorphous, anatase, brookite and rutile forms), aluminum (amorphous, alpha, and gamma forms), and boronitride (cubic form),
In certain embodiments, the substantially nonporous core materials are composite materials. Composite materials describe the engineered materials of the invention composed of one or more components described herein in combination with dispersed nanoparticles, wherein each component/nanoparticle remains separate and distinct on a macroscopic level within the finished structure. The composite material of the present invention is independent of form, and may be monolithic or particulate in nature. Moreover, the short-hand convention used herein to describe a composite material containing a dispersed nanoparticle, Np/(A)w(B)x(C)y, may be understood as follows: the symbolic representation to the left of the slash mark represents the dispersed nanoparticle, and the symbolic representations to the right of the slash mark represent the components that comprise the material that the nanoparticle (noted on the left of the slash mark) is dispersed within. In certain embodiments, the composite materials of the present invention may be nanocomposites, which are known to include, at least, for example, nano/nano-type, intra-type, inter-type, and intra/inter-type. (Nanocomposites Science and Technology, edited by P. M. Ajayan, L. S. Schadler, P. V. Braun, Wiley-VCH (Weinheim, Germany), 2003) The term“nanoparticle” is a microscopic particle/grain or microscopic member of a powder/nanopowder with at least one dimension less than about 100 nm, e.g., a diameter or particle thickness of less than about 100 nm (0.1 μm), which may be crystalline or noncrystalline.
Nanoparticles have properties different from, and often superior to those of conventional bulk materials including, for example, greater strength, hardness, ductility, sinterability, and greater reactivity among others. Considerable scientific study continues to be devoted to determining the properties of nanomaterials, small amounts of which have been synthesized (mainly as nano-size powders) by a number of processes including colloidal precipitation, mechanical grinding, and gas-phase nucleation and growth. Extensive reviews have documented recent developments in nano-phase materials, and are incorporated herein by reference thereto: Gleiter, H. (1989) “Nano-crystalline materials,” Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis and properties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. In certain embodiments, the nanoparticles comprise oxides or nitrides of the following: silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In certain embodiments, the nanoparticles of the present invention are selected from diamonds, zirconium oxide (amorphous, monoclinic, tetragonal and cubic forms), titanium oxide (amorphous, anatase, brookite and mtile forms), aluminum (amorphous, alpha, and gamma forms), and boronitride (cubic form). In particular embodiments, the nanoparticles of the present invention are selected from nano-diamonds, silicon carbide, titanium dioxide (anatase form), cubic-boronitride, and any combination thereof. Moreover, in particular embodiments, the nanoparticles may be crystalline or amorphous. In particular embodiments, the nanoparticles are less than or equal to 100 nm in diameter, e.g., less than or equal to 50 nm in diameter, e.g., less than or equal to 20 nm in diameter.
Moreover, it should be understood that the nanoparticles that are characterized as dispersed within the composites of the invention are intended to describe exogenously added nanoparticles. This is in contrast to nanoparticles, or formations containing significant similarity with putative nanoparticles, that are capable of formation in situ, wherein, for example, macromolecular structures, such as particles, may comprise an aggregation of these endogenously created.
Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures. A bulk material should have constant physical properties regardless of its size, but at the nano-scale this is often not the case. Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials.
In certain embodiments, the composite materials include magnetic materials, materials having a high thermal conductivity, or mixtures thereof. Similarly, in certain embodiments, the cores themselves are magnetic materials, materials having a high thermal conductivity or mixtures thereof.
Materials having a high thermal conductivity, high thermal conductivity cores or a high thermal conductivity additives are defined as materials having a thermal conductivity greater than 20 W/(m·K). In various embodiments the additive has a thermal conductivity ranges from: about 20 W/(m·K) to not more than 3500 W/(m·K); about 100 W/(m·K) to not more than 3300 W/(m·K); and 400 W/(m·K) to not more than 3000 W/(m·K). This high thermal conductivity additive can be a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamonds.
A high thermal diffusivity additive is defined as an additive used in a superficially porous particle having a thermal diffusivity greater than 20 mm2/s. In various embodiments the additive has a thermal diffusivity ranges from: about 20 mm2/s to not more than 2000 mm2/s; about 100 mm2/s to not more than 1600 mm2/s; and 150 mm2/s to not more than 1400 mm2/s. This high thermal conductivity additive can be a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamonds.
A magnetic material include materials that have a mass magnetization (a, magnetic moment per unit mass, magnetic saturation or saturation magnetization) at room temperature greater than 15 emu/g (A m2/kg). This includes ferromagnetic and ferrimagnetic materials, including (but is not limited to): magnetite (ferrous ferric oxide); maghemite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co). Magnetic core particles do not include other oxides of iron, including hematite and goethite, that have mass magnetization values less than 10 emu/g. Hematite (0.4 emu/g) is considered antiferromagnetic at room temperature.
In one embodiment, the cores are spherical. In a further embodiment, the spherical core has a non-crystalline or amorphous molecular ordering. In a further embodiment, the spherical core has a non-periodic pore structure.
In another embodiment, the core has an average size of about 0.1 μm to about 300 μm. In a further embodiment, the core has an average size of about 0.1 μm to about 30 μm. In a further embodiment, the core has an average size of about 0.5 μm to about 30 μm. In a further embodiment, the core has an average size of about 0.6 μm to about 10 μm. In a further embodiment, the core has an average size of about 1.0 μm to about 3.0 μm.
In certain embodiments, the core material of the invention a substantially narrow particle size distribution. In certain other embodiments, the 90/10 ratio of particle sizes is from 1.00-1.55. In specific embodiments, the 90/10 ratio of particle sizes is from 1.00-1.10 or from 1.05-1.10. In other specific embodiments, the 90/10 ratio of particle sizes is from 1.10-1.55; from 1.10-1.50; or from 1.30-1.45.
In certain embodiments, the coated core is hydrolytically stable at a pH of about 1 to about 14. In one embodiment, the coated core is hydrolytically stable at a pH of about 10 to about 14. In another embodiment, the coated core is hydrolytically stable at a pH of about 1 to about 5.
In certain aspects, the core material comprises a core-coating material.
The composition of the core-coating material may be varied by one of ordinary skill in the art to provide enhanced chromatographic selectivity, enhanced particle chemical stability, enhanced column efficiency, and/or enhanced mechanical strength. Similarly, the composition of the surrounding material provides a change in hydrophilic/lipophilic balance (HLB), surface charge (e.g., isoelectric point or silanol pKa), and/or surface functionality for enhanced chromatographic separation. Furthermore, in some embodiments, the composition of the surrounding material may also provide a surface functionality for available for further surface modification.
In certain aspects, the core-coating material may be an inorganic material; an organic material; or an inorganic/organic hybrid material.
The coated core may be independently derived from:
In certain aspects, the inorganic portion of the core-coating material is independently selected from the group consisting of alumina, silica, titania, cerium oxide, or zirconium oxides, and ceramic materials.
Alternatively, the coated core may independently derived from:
The coated core may be independently porous or nonporous. Furthermore, the pore structure of the coated core may independently possess or not possess an ordered pore structure. In certain aspects, the coated core may have a chromatographically enhancing pore geometry (CEPG).
In other aspects, the core-coating material may independently comprise from about 0-100 mol % hybrid material. The inorganic portion of the core-coating material may independently be alumina, silica, titanium oxide, cerium oxide, zirconium oxide or ceramic materials or a mixture thereof.
In specific aspects, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 0 molar % to not more than about 25 molar %, wherein the pores of the coated core are substantially disordered. Similarly, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 25 molar % to not more than about 50 molar %, wherein the pores of the coated core are substantially disordered, and wherein the core-coating material independently possesses a chromatographically enhancing pore geometry (CEPG). In certain embodiments, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 50 molar % to not more than about 75 molar %, wherein the pores of the coated core are substantially disordered, and wherein the coated core independently possesses a chromatographically enhancing pore geometry (CEPG). In still other embodiments, the inorganic portion of the core-coating material may independently be present in an amount ranging from about 75 molar % to not more than about 100 molar %, wherein the pores of the c coated core are substantially disordered, and wherein the coated core independently possesses a chromatographically enhancing pore geometry (CEPG).
In some aspects, the core-coating material may comprise a material of formula I:
(SiO2)d/[R2((R)p(R1)qSiOt)m]; (I)
wherein,
when 0<p+q≤3; and
when p+q≤2.
In other aspects, the core-coating material may comprise a material of formula II:
(SiO2)d/[(R)p(R1)qSiOt] (II);
wherein,
In still other aspects, the core-coating material may comprise a material of formula III:
(SiO2)d/[R2((R1)rSiOt)m] (III)
wherein,
In yet aspects, the core-coating material may comprise a material of formula IV:
(A)x(B)y(C)z (IV),
wherein the order of repeat units A, B, and C may be random, block, or a combination of random and block;
In still yet other aspects, the core-coating material may comprise a material of formula V:
(A)x(B)y(B*)y*(C)z (V),
wherein the order of repeat units A, B, B*, and C may be random, block, or a combination of random and block;
In certain aspects, R2 in the formulas presented above may be present or absent.
In certain aspects, R1 in the formulas presented above is C1-C18 alkyl group substituted by hydroxyl. In still other aspects, R1 in the formulas presented above is hydroxypropyl. In still other aspects, the hydroxy substituted alkyl group is further functionalized by an isocyanate. In yet other aspects, the isocyanate is Octadecyl isocyanate, Dodecyl isocyanate, Pentafluorophenyl isocyanate, 4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, 2-cyanophenyl isocyanate, phenyl isocyate, benzyl isocyanate, phenethyl isocyanate or diphenylethyl isocyante.
In another aspect, the invention provides materials as described herein wherein the core-coating material further comprises a nanoparticle or a mixture of more than one nanoparticles dispersed within the core-coating material.
In certain embodiments, the nanoparticle is present in <20% by weight of the nanocomposite, <10% by weight of the nanocomposite, or <5% by weight of the nanocomposite.
In other embodiments, the nanoparticle is crystalline or amorphous and may be silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, oxides thereof, or a nitride thereof. In particular embodiments, the nanoparticle is a substance which comprises one or more moieties selected from the group consisting of nano-diamonds, silicon carbide, titanium dioxide, cubic-boronitride.
In other embodiments, the nanoparticles may be less than or equal to 200 μm in diameter, less than or equal to 100 μm in diameter, less than or equal to 50 μm in diameter, or less than or equal to 20 μm in diameter.
In some embodiments, a core coated with a core coating material may be subsequently coated with one or more layers of those same core-coating materials. If the core is coated with multiple layers, the final layer (or any layer in between) may independently be the same or different to allow for proper attachment of additional layers of coating material and/or for the attachment of the porous layer.
Porous Shell Layer Material
The materials of the invention have one or more layers of a porous shell material applied to the coated core. In certain embodiments, one or more layers of porous shell material are a porous inorganic/organic hybrid material; a porous silica or a porous composite material. In certain embodiments, the porous shell material is comprised of nonporous sols or particles which, upon application, form a porous shell.
In certain aspects, the materials of the invention have a rough surface. In still other aspects, the materials of the invention have a smooth surface.
In certain embodiments, each porous layer is independently from 0.02 μm to 5 μm in thickness as measured perpendicular to the surface of the nonporous core.
In other embodiments, each porous layer is independently from 0.06 μm to 1 μm in thickness as measured perpendicular to the surface of the nonporous core.
In still other embodiments, each porous layer is independently from 0.20 μm to 0.70 μm. in thickness as measured perpendicular to the surface of the nonporous core.
In certain embodiments, the materials of the invention have between 1 and 15 layers of porous shell material. In other embodiments between 2 and 5 layers of porous shell material. In still others 1 or 2 layers of porous shell materials.
Porous Hybrids
In certain embodiments, the porous hybrid layer material or shell material which may be layered onto the core may be independently derived from:
In certain aspects, the inorganic portion of the porous hybrid layer material or shell material is independently selected from the group consisting of alumina, silica, titania, cerium oxide, or zirconium oxides, and ceramic materials.
Alternatively, the porous hybrid layer material or shell material may independently derived from:
In other aspects, the porous hybrid layer material or shell material may independently comprise from about 0-100 mol % hybrid material. The inorganic portion of the porous hybrid layer material or shell material may independently be alumina, silica, titanium oxide, cerium oxide, zirconium oxide or ceramic materials or a mixture thereof.
In specific aspects, the inorganic portion of the porous hybrid layer material or shell material may independently be present in an amount ranging from about 0 molar % to not more than about 25 molar %, wherein the pores of the core-coating material are substantially disordered. Similarly, the inorganic portion of the porous hybrid layer material or shell material may independently be present in an amount ranging from about 25 molar % to not more than about 50 molar %, wherein the pores of the porous hybrid layer or shell are substantially disordered, and wherein the porous hybrid layer or shell may or may not independently possesses a chromatographically enhancing pore geometry (CEPG). In certain embodiments, the inorganic portion of the porous hybrid layer material or shell material I may independently be present in an amount ranging from about 50 molar % to not more than about 75 molar %, wherein the pores of the hybrid layer or shell are substantially disordered, and wherein the hybrid layer material independently possesses a chromatographically enhancing pore geometry (CEPG). In still other embodiments, the inorganic portion of the porous hybrid layer material or shell material may independently be present in an amount ranging from about 75 molar % to not more than about 100 molar %, wherein the pores of the porous hybrid layer or shell are substantially disordered, and wherein the porous hybrid layer or shell may or may not independently possesses a chromatographically enhancing pore geometry (CEPG).
In still other aspects, the inorganic portion of the porous hybrid layer material or shell material may independently be present in an amount ranging from about 0 molar % to not more than about 100 molar %; specifically, 0%-10%, 0%-5%, 0%-4%, 0%-3%, 0%-2%, 0%-1%, 1%-10%, 1%-5%, 1%-4%, 1%-3%, 1%-2%, 5%-100%, 10%-100%, 15%-100%, 20%-100%, 25%-100%, 30%-100%, 35%-100%, 40%-100%, 45%-100%, 55%-100%, 60%-100%, 65%-100%, 70%-100%, 75%-100%, 80%-100%, 81%-100%, 82%-100%, 83%-100%, 84%-100%, 85%-100%, 86%-100%, 87%-100%, 88%-100%, 89%-100%, 90%-100%, 91%-100%, 92%-100%, 93%-100%, 94%-100%, 95%-100%, 96%-100%, 97%-100%, 98%-100%, or 99%-100%.
In some aspects, the porous hybrid layer material or shell material may comprise a material of formula I:
(SiO2)d/[R2((R)p(R1)qSiOt)m]; (I)
wherein,
when 0<p+q≤3; and
when p+q≤2.
In other aspects, the porous hybrid layer material or shell material may comprise a material of formula II:
(SiO2)d/[(R)p(R1)qSiOt] (II);
wherein,
In still other aspects, the porous hybrid layer material or shell material may comprise a material of formula III:
(SiO2)d/[R2((R1)rSiOt)m] (III)
wherein,
In yet aspects, the porous hybrid layer material or shell material may comprise a material of formula IV:
(A)x(B)y(C)z (IV),
wherein the order of repeat units A, B, and C may be random, block, or a combination of random and block;
In still yet other aspects, the porous hybrid layer material or shell material may comprise a material of formula V:
(A)x(B)y(B*)y*(C)z (V),
wherein the order of repeat units A, B, B*, and C may be random, block, or a combination of random and block;
In certain aspects, R2 in the formulas presented above may be present or absent.
In certain aspects, R1 in the formulas presented above is C1-C18 alkyl group substituted by hydroxyl. In still other aspects, R1 in the formulas presented above is hydroxypropyl. In still other aspects, the hydroxy substituted alkyl group is further functionalized by an isocyanate. In yet other aspects, the isocyanate is octadecyl isocyanate, dodecyl isocyanate, pentafluorophenyl isocyanate, 4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, 2-cyanophenyl isocyanate, phenyl isocyate, benzyl isocyanate, phenethyl isocyanate or diphenylethyl isocyante.
In certain embodiments, the organosiloxane is, without limitation, phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane; hexyltrimethoxysilane; chloropropyltriethoxysilane; chloropropyltrimethoxysilane; octadecyltrimethoxysilane; octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane; 3,3.3-trifluoropropyltrimethoxysilane; 3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and 3-cyanobutyltrimethoxysilane alone or in a mixture with tetraethoxysilane or tetramethoxysilane.
In another embodiment, the organosiloxane is, without limitation, a substituted benzene, including (but not limited to) 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane.
In another aspect, the invention provides materials as described herein wherein the porous hybrid layer material or shell material further comprises a nanoparticle or a mixture of more than one nanoparticles dispersed within the layer or shell material.
In certain embodiments, the nanoparticle is present in <20% by weight of the nanocomposite, <10% by weight of the nanocomposite, or <5% by weight of the nanocomposite.
In other embodiments, the nanoparticle is crystalline or amorphous and may be silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, oxides thereof, or a nitride thereof. In particular embodiments, the nanoparticle is a substance which comprises one or more moieties selected from the group consisting of nano-diamonds, silicon carbide, titanium dioxide, cubic-boronitride.
In other embodiments, the nanoparticles may be less than or equal to 200 μm in diameter, less than or equal to 100 μm in diameter, less than or equal to 50 μm in diameter, or less than or equal to 20 μm in diameter.
Porous Silica
In certain embodiments, the porous shell layer materials are porous silica or other metal oxides such as alumina, titanium oxides or cerium oxide.
Porous Composites.
In certain embodiments, the porous shell layer materials are composite materials. Composite materials describe the engineered materials of the invention composed of one or more components described herein in combination with dispersed nanoparticles, wherein each component/nanoparticle remains separate and distinct on a macroscopic level within the finished structure. The composite material of the present invention is independent of form, and may be monolithic or particulate in nature. Moreover, the short-hand convention used herein to describe a composite material containing a dispersed nanoparticle, Np/(A)w(B)x(C)y, may be understood as follows: the symbolic representation to the left of the slash mark represents the dispersed nanoparticle, and the symbolic representations to the right of the slash mark represent the components that comprise the material that the nanoparticle (noted on the left of the slash mark) is dispersed within. In certain embodiments, the composite materials of the present invention may be nanocomposites, which are known to include, at least, for example, nano/nano-type, intra-type, inter-type, and intra/inter-type. (Nanocomposites Science and Technology, edited by P. M. Ajayan, L. S. Schadler, P. V. Braun, Wiley-VCH (Weinheim, Germany), 2003) The term “nanoparticle” is a microscopic particle/grain or microscopic member of a powder/nanopowder with at least one dimension less than about 100 nm, e.g., a diameter or particle thickness of less than about 100 nm (0.1 μm), which may be crystalline or noncrystalline.
Nanoparticles have properties different from, and often superior to those of conventional bulk materials including, for example, greater strength, hardness, ductility, sinterability, and greater reactivity among others. Considerable scientific study continues to be devoted to determining the properties of nanomaterials, small amounts of which have been synthesized (mainly as nano-size powders) by a number of processes including colloidal precipitation, mechanical grinding, and gas-phase nucleation and growth. Extensive reviews have documented recent developments in nano-phase materials, and are incorporated herein by reference thereto: Gleiter, H. (1989) “Nano-crystalline materials,” Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis and properties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. In certain embodiments, the nanoparticles comprise oxides or nitrides of the following: silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In certain embodiments, the nanoparticles of the present invention are selected from diamonds, zirconium oxide (amorphous, monoclinic, tetragonal and cubic forms), titanium oxide (amorphous, anatase, brookite and rutile forms), aluminum (amorphous, alpha, and gamma forms), and boronitride (cubic form). In particular embodiments, the nanoparticles of the present invention are selected from nano-diamonds, silicon carbide, titanium dioxide (anatase form), cubic-boronitride, and any combination thereof. Moreover, in particular embodiments, the nanoparticles may be crystalline or amorphous. In particular embodiments, the nanoparticles are less than or equal to 100 nm in diameter, e.g., less than or equal to 50 nm in diameter, e.g., less than or equal to 20 nm in diameter.
Moreover, it should be understood that the nanoparticles that are characterized as dispersed within the composites of the invention are intended to describe exogenously added nanoparticles. This is in contrast to nanoparticles, or formations containing significant similarity with putative nanoparticles, that are capable of formation in situ, wherein, for example, macromolecular structures, such as particles, may comprise an aggregation of these endogenously created.
Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures. A bulk material should have constant physical properties regardless of its size, but at the nano-scale this is often not the case. Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials.
In certain embodiments, the composite materials include magnetic materials, materials having a high thermal conductivity, or mixtures thereof.
Materials having a high thermal conductivity, high thermal conductivity cores or a high thermal conductivity additive is defined as a material, core or additive used in a superficially porous particle having a thermal conductivity greater than 20 W/(m·K). In various embodiments the core or additive has a thermal conductivity ranges from: about 20 W/(m·K) to not more than 3500 W/(m·K); about 100 W/(m·K) to not more than 3300 W/(m·K); and 400 W/(m·K) to not more than 3000 W/(m·K). This high thermal conductivity core or additive can be a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity core or additive includes (but is not limited to) aluminum, copper, gold, and diamonds.
A high thermal diffusivity additive is defined as an additive used in a superficially porous particle having a thermal diffusivity greater than 20 mm2/s. In various embodiments the additive has a thermal diffusivity ranges from: about 20 mm2/s to not more than 2000 mm2/s; about 100 mm2/s to not more than 1600 mm2/s; and 150 mm2/s to not more than 1400 mm2/s. This high thermal conductivity additive can be a 0.1-8 μm core particle, nanoparticle additives, or a metal oxide precursor. In various embodiments the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamonds.
A magnetic material include materials that have a mass magnetization (o, magnetic moment per unit mass, magnetic saturation or saturation magnetization) at room temperature greater than 15 emu/g (A m2/kg). This includes ferromagnetic and ferrimagnetic materials, including (but is not limited to): magnetite (ferrous ferric oxide); maghemite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co). Magnetic core particles do not include other oxides of iron, including hematite and goethite, that have mass magnetization values less than 10 emu/g. Hematite (0.4 emu/g) is considered antiferromagnetic at room temperature.
Gradient Materials
In certain embodiments, the superficially porous materials of the invention utilize core materials having an increased hybrid content near the surface of the coated core.
In other embodiments, the superficially porous material of the invention utilize core materials having a decreased hybrid content near the surface of the coated core.
In such cases, such increase or decrease generally occurs within 1-200 nm of the surface of the core; alternatively within 5-60 nm of the surface of the core.
Similarly, in certain embodiments, the superficially porous materials of the invention include superficially porous materials having an increased hybrid content near the surface of the material. In other embodiments, the superficially porous material of the invention include superficially porous materials having a decreased hybrid content near the surface of the material.
In such cases, such increase or decrease generally occurs within 1-200 nm of the surface of the superficially porous material; alternatively within 5-60 nm of the surface of the superficially porous material.
Core and Material Morphology
In certain embodiments, the superficially porous material of the invention has specific core morphology. In certain embodiments, such core morphology is produced by using core materials having the defined shape. In certain other embodiments, the core morphology refers to the specific defined shape of the product material of the invention.
In certain embodiments, the cores or the product material has a highly spherical, rod shaped, bent-rod shaped, toroid shaped or dumbbell shaped core morphology.
In certain other embodiments, the cores or the product material has a mixture of highly spherical, rod shaped, bent-rod shaped, toroid shaped or dumbbell shaped core morphologies.
Core and Material Properties.
The superficially porous material of the invention have significantly higher thermal conductivity than comparable fully porous silica particles, particularly of the same size. In certain embodiments, the superficially porous material of the invention have significantly higher thermal conductivity than comparable superficially porous silica particles, particularly of the same size. Determination of particle thermal conductivity can be made by the method of Gritti and Guiochon [J. Chromatogr. A, 2010, 1217, 5137) taking into account differences in bulk material properties, pore volume, surface modification type and coverage.
The superficially porous material of the invention have significantly improved chemical stability when exposed to high pH mobile phases as compared to unbonded, fully porous silica particles, particularly of the same size. In certain embodiments, the superficially porous material of the invention have significantly improved chemical stability when exposed to high pH mobile phases as compared to unbonded, superficially porous silica particles, particularly of the same size.
The superficially porous material of the invention are capable of forming a packed bed with improved permeability as compared to fully porous silica particles, particularly of the same size. In certain embodiments, the superficially porous material of the invention are capable of forming a packed bed with improved permeability as compared to superficially porous silica particles, particularly of the same size. Improved permeability for a give particle size is observed as a decrease in column backpressure. Determination of permeability of packed beds can be made by inverse size exclusion chromatography.
The superficially porous materials (which are particles) have an average particle size of the material is between 0.8-20.0 μm. Specifically, the average particle size of the material may be between 0.8-3.0 μm, between 1.1-2.9 μm or between 1.3-2.7 μm.
The superficially porous materials have pores which have an average diameter of about 25-600 Å; about 60-350 Å; about 80-300 Å; or about 90-150 Å.
The superficially porous materials have an average pore volume of about 0.05-1.0 cm3/g; of about 0.09-0.50 cm3/g; about 0.09-0.45 cm3/g; or about 0.17-0.30 cm3/g.
The superficially porous materials have a surface area between about 10 m2/g and 600 m2/g.
The materials of the invention may further be surface modified.
Thus, in one embodiment, the material as described herein may be surface modified with a surface modifier having the formula Za(R′)bSi—R″, where Z═Cl, Br, I, C1-C5 alkoxy, dialkylamino or trifluoromethanesulfonate; a and b are each an integer from 0 to 3 provided that a+b=3; R′ is a C1-C6 straight, cyclic or branched alkyl group, and R″ is a functionalizing group.
In another embodiment, the materials have been surface modified by coating with a polymer.
In certain embodiments, R′ is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl, isopentyl, hexyl and cyclohexyl. In other embodiments, R′ is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cyano, amino, diol, nitro, ester, a cation or anion exchange group, an alkyl or aryl group containing an embedded polar functionality and a chiral moiety. In certain embodiments, R′ is selected from the group consisting of aromatic, phenylalkyl, fluoroaromatic, phenylhexyl, pentafluorophenylalkyl and chiral moieties.
In one embodiment, R″ is a C1-C30 alkyl group. In a further embodiment, R″ comprises a chiral moiety. In another further embodiment, R″ is a C1-C20 alkyl group.
In certain embodiments, the surface modifier comprises an embedded polar functionality. In certain embodiments, such embedded polar functionality includes carbonate, amide, urea, ether, thioether, sulfinyl, sulfoxide, sulfonyl, thiourea, thiocarbonate, thiocarbamate, ethylene glycol, heterocyclic, or triazole functionalities. In other embodiments, such embedded polar functionality includes carbamate functionalities such as disclosed in U.S. Pat. No. 5,374,755, and chiral moieties. Such groups include those of the general formula
wherein l, m, o, r and s are 0 or 1, n is 0, 1, 2 or 3 p is 0, 1, 2, 3 or 4 and q is an integer from 0 to 19; R3 is selected from the group consisting of hydrogen, alkyl, cyano and phenyl; and Z, R′, a and b are defined as above. Advantageously, the carbamate functionality has the general structure indicated below:
wherein R5 may be, e.g., cyanoalkyl, t-butyl, butyl, octyl, dodecyl, tetradecyl, octadecyl, or benzyl. Advantageously, R5 is octyl, dodecyl, or octadecyl.
In certain embodiments, the surface modifier is selected from the group consisting of phenylhexyltrichlorosilane, pentafluorophenylpropyltrichlorosilane, octyltrichlorosilane, octadecyltrichlorosilane, octyldimethylchlorosilane and octadecyldimethylchlorosilane. In some embodiments, the surface modifier is selected from the group consisting of octyltrichlorosilane and octadecyltrichlorosilane. In other embodiments, the surface modifier is selected from the group consisting of an isocyanate or 1,1′-carbonyldiimidazole (particularly when the hybrid group contains a (CH2)3OH group).
In another embodiment, the material has been surface modified by a combination of organic group and silanol group modification.
In still another embodiment, the material has been surface modified by a combination of organic group modification and coating with a polymer. In a further embodiment, the organic group comprises a chiral moiety.
In yet another embodiment, the material has been surface modified by a combination of silanol group modification and coating with a polymer.
In other embodiments, the material has been surface modified via formation of an organic covalent bond between the particle's organic group and the modifying reagent.
In still other embodiments, the material has been surface modified by a combination of organic group modification, silanol group modification and coating with a polymer.
In another embodiment, the material has been surface modified by silanol group modification.
The invention provides a method for preparing a superficially porous material comprising:
In certain embodiments, the method further provides the step of:
The approaches described herein allows for the synthesis of narrow particle size distribution fully porous, spherical particles as well as narrow particle size distribution superficially porous (defined as a porous shell layer on a nonporous core particle) particles having a chromatographically enhanced pore geometry. The processes involves the condensation of a tetraalkoxysilane (e.g., tetraethoxysilane or tetramethoxysilane) alone or co-condensed with a second organosilane through modification of a traditional Stober-growth process. Listed below are non-limiting descriptions of this process. In each instance the core material may be coated as described herein before the addition of the superficially porous materials
Step 1) Condensation of a tetralkoxysilane with or without (R1)a(R2)b(R3)cSi(OR4)d to form seed particles (0.2-10 μm) in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 2) Grow seed particles by condensation of a tetrmalkoxysilane with or without (R1)a(R2)b(R3)cSi(OR4)d to form larger core particles (0.3-20 μm) in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 3) Further grow particles by co-condensation of a tetraalkoxysilane with (R1)a(R2)b(R3)cSi(OR4)d to yield non-porous particles (0.4-20 μm) in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 4) Improve particle size distribution through particle classification techniques.
Step 5) Produce a porous silica particle by removal of organic group and or surfactants by thermal treatment.
Step 6) Pore structure modification using fluorine containing chemical techniques, including ammonium bifluoride and hydrofluoric acid.
Step 7) Pore structure modification by hydrothermal processing in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 8) Improve particle size distribution through particle classification techniques.
Step 9) Use of elevated temperature treatment (>600° C.) to improve particle mechanical stability.
Step 10) Prepare the particle surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).
Step 11) Chemical modification of the particle surface
Step 1) Condensation of a tetraalkoxysilane with or without (R1)a(R2)b(R3)cSi(OR4)d to form seed particles (0.2-10 μm) in the presence or absence of surfactants or pore structuring agents.
Step 2) Grow seed particles by condensation of a tetraalkoxysilane with or without (R1)a(R2)b(R3)cSi(OR4)d to form larger core particles (0.3-20 μm) in the presence or absence of surfactants or pore structuring agents.
Step 3) Further grow particles by co-condensation of a tetraalkoxysilane with (R1)a(R2)b(R3)cSi(OR4)d to yield non-porous particles (0.4-20 μm) in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 4) Improve particle size distribution through particle classification techniques
Step 5) Produce a porous silica particle by removal of organic group and/or surfactants by thermal treatment or extraction techniques.
Step 6) Pore structure modification using fluorine containing chemical techniques, including ammonium bifluoride and hydrofluoric acid.
Step 7) Pore structure modification by pseudomorphic transformation in the presence of surfactants and/or pore structuring agents (including pore expanding molecules and polymers).
Step 8) Surfactant removal by extraction techniques or by calcination.
Step 9) Pore structure modification by hydrothermal processing in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 10) Improve particle size distribution through particle classification techniques
Step 11) Use of elevated temperature treatment (>600° C.) to improve particle mechanical stability.
Step 12) Prepare the particle surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).
Step 13) Chemical modification of the particle surface.
Step 1) Condensation of Si(OCH2CH3)4 to form seed particles (0.2-2 μm)
Step 2) Grow seed particles by condensation of Si(OCH2CH3)4 to form a larger core particle (0.3-7 μm).
Step 3) Further grow particles by co-condensation of Si(OCH2CH3)4 with RSi(OR′)3 (R=octyl or octadecyl and R′ is methyl or ethyl) to yield non-porous particle (0.4-10 μm) in the presence or absence of a pore structuring agent (e.g., mesitylene or an alkane). Here R=octyl or octadecyl and R′ is methyl or ethyl.
Step 4) Improve particle size distribution through particle classification techniques
Step 5) Produce a porous silica particle by removal of organic group by thermal treatment (500-600° C. in air).
Step 6) Pore structure modification using ammonium bifluoride (4-20 hours, 25-60° C.).
Step 7) Pore structure modification by hydrothermal processing (7-20 hours, pH 5-7, 90-150° C.).
Step 8) Improve particle size distribution through particle classification techniques
Step 9) Use of elevated temperature treatment (800-1,000° C.) to improve particle mechanical stability.
Step 10) Prepare the particle surface for modification using hydrofluoric acid treatment.
Step 11) Chemical modification of the particle surface using chlorosilanes coupling and endcapping protocols.
Step 1)<10 μm particles (e.g., diamonds, zirconia, titania, iron oxides, cerium, cobalt, cobalt oxides, carbon, silica, silica carbide) are surface activated through treatment with acid, base, chemical reduction, chemical oxidation, or through attachment of a surface modifying group (e.g., adsorption of an amine, surfactant, silane bond).
Step 2) Particles are grown by condensation of a tetraalkoxysilane with or without (R1)a(R2)b(R3)cSi(OR4)d in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 3) Particle are further grown by co-condensation of a tetraalkoxysilane with (R1)a(R2)b(R3)cSi(OR4)d to yield a non-porous particles in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 4) Improve particle size distribution through particle classification techniques
Step 5) Produce a porous silica particle by removal of organic group and/or surfactants by thermal treatment or extraction techniques.
Step 6) Pore structure modification using fluorine containing chemical techniques, including ammonium bifluoride and hydrofluoric acid.
Step 7) Pore structure modification by pseudomorphic transformation in the presence of surfactants and/or pore structuring agents (including pore expanding molecules and polymers).
Step 8) Surfactant removal by extraction techniques or by calcination.
Step 9) Pore structure modification by hydrothermal processing in the presence or absence of surfactants or pore structuring agents (including pore expanding molecules and polymers).
Step 10) Improve particle size distribution through particle classification techniques
Step 11) Use of elevated temperature treatment (>600° C.) to improve particle mechanical stability.
Step 12) Prepare the particle surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).
Step 13) Chemical modification of the particle surface
Many alternatives within a Method A-D can be explored. For example, if particle are substantially uniform in size after growth, further sizing steps may not be required. Other steps that may be avoided are the use of fluorine containing chemical modification step before pseudomorphic transformation, or the use of a higher temperature treatment to improve particle mechanical stability if the particles already have sufficient mechanical strength without the use of this step.
Method D may be useful for preparing superficially porous magnetic particles.
Other Approaches which Will be Useful in the Methods of the Invention are as Follows.
In one aspect, the invention provides a method for preparing a superficially porous material comprising:
In certain embodiments, the method for preparing a superficially porous material further comprises the step of:
In other embodiments, each layer of porous shell material wherein each layer is independently selected from a porous inorganic/organic hybrid material, a porous silica, a porous composite material or mixtures thereof.
In still other embodiments, each layer of porous shell material is applied using sols, a polyelectrolyte or a chemically degradable polymer, wherein:
In certain embodiments, each layer of porous shell material is applied by formation through an electrostatic or acid/base interaction of an ionizable group comprising the steps of:
In particular embodiments, the prebonding of the substantially nonporous core or sols includes washing with and acid or base, or a charged polyelectrolyte. In other embodiments, the prebonding of the substantially nonporous core or sols includes chemical transformation of an accessible hybrid organic group.
In still other embodiments the accessible hybrid organic group is an aromatic group that can undergo sulfonation, nitration, amination, or chloromethylation followed by oxidation or nucleophillic displacement with amine containing groups to form ionizable groups. In yet other embodiments, the accessible hybrid organic group is an alkene group that can undergo oxidation, cross-metathesis, or polymerization to form ionizable groups. In specific embodiments, the accessible hybrid organic group is an thiol group that can undergo oxidation, radical addition, nucleophillic displacement, or polymerization to form ionizable groups.
In yet other embodiments, the prebonding of the substantially nonporous core or sols includes bonding with an alkoxysilane that has an ionizable group of equation 1,
R(CH2)nSi(Y)3-x(R′)x (equation 1)
In still yet other embodiments, the prebonding of the substantially nonporous core or sols includes bonding with an alkoxysilane that has an ionizable group of equation 2,
A(CH2)nSi(Y)3-x(R′)x (equation 2)
R′ independently represents an alkyl, branched alkyl, aryl, or cycloalkyl group.
In particular embodiments, each layer of porous shell material is applied using a polyelectrolyte or a chemically degradable polymer.
In other embodiments, the polyelectrolyte or a chemically degradable is removed from the material by chemical extraction, degradation, or thermal treatment at temperatures less than 600° C., or combinations thereof.
In certain embodiments, each layer of porous shell material is applied using alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, comprising the steps of:
In particular embodiments, the alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, are condensed on the substantially nonporous core in a solution comprising ethanol, water, ammonium hydroxide, an ionic surfactant; and a non-ionic surfactant.
In other embodiments, the ionic surfactant is C10-C30N(R)3+X−, where R is methyl, ethyl, propyl, alkyl, fluoroalkyl; X is a halogen, hydroxide, or of the form R′SO3− or R′CO2− where R′ is methyl, ethyl, butyl, propyl, isopropyl, tert-butyl, aryl, tolyl, a haloalkyl or a fluoroalkyl group.
In yet other embodiments, the ionic surfactant is octadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, or dodecyltrimethylammonium chloride.
In particular embodiments, the concentration of ionic surfactant is maintained in the reaction solution between 5-17 mM; or in certain embodiments between 8-14 mM.
In other embodiments, the non-ionic surfactant is a diblock or triblock copolymer. In certain embodiments, the copolymer is (PEO)x(PPO)y(PEO)x,
wherein
In particular embodiments the triblock copolymer is Pluronic® P123, having (PEO)20(PPO)70(PEO)20. In still other embodiments, the alkoxysilanes, organoalkoxysilanes, or combinations thereof, are condensed on the substantially nonporous core in a solution comprising:
In certain embodiments, the alkoxysilane used is selected from the group of tetramethoxsilane or tetraethoxysilane.
In still other embodiments, the organosiloxane is selected from the group of phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane, diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 2-bis(triethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; or 1,3-bis(trimethoxysilylethyl)benzene.
In yet other embodiments, the alkoxysilane used is tetraethoxysilane and the organoalkoxysilane used is 1,2-bis(triethoxysilyl)ethane.
In certain other embodiments, the concentration of octadecyltrimethylammonium bromide is maintained between 8-14 mM.
In certain other embodiments, the molar ratio of octadecyltrimethylammonium bromide and Pluronic® P123 is maintained at or above 1.30.
In still other embodiments, the molar ratio of alkoxysilane to organoalkoxysilane ranges between 30:1 to 1:30.
In certain embodiments, alkoxysilane, organoalkoxysilane, or combinations thereof are prediluted in ethanol. In certain such embodiments, prediluted ethanol solutions of alkoxysilane, organoalkoxysilane, or combinations thereof are added at a slow and constant rate to prevent fines generation, aggregation and agglomeration. In other such embodiments, prediluted ethanol solutions of alkoxysilane, organoalkoxysilane, or combinations thereof are added a rate between 5-500 μL/min.
In other embodiments, a secondary solution comprising ethanol, water, ammonium hydroxide, ionic surfactant and non-ionic surfactant is added at a slow and constant rate to prevent fines generation, aggregation and agglomeration. In certain such embodiments the secondary solution comprising ethanol, water, ammonium hydroxide, ionic surfactant and non-ionic surfactant is added within a range between the rate required to maintain a uniform ratio of particle surface area (m2) to reaction volume, to the rate required to maintain a uniform ratio of particle volume (m3) to reaction volume.
In certain embodiments, the surfactant mixture is removed through one or more of the following; extractions with acid, water, or organic solvent; ozonolysis treatments, thermal treatments<600° C., or thermal treatments between 500-1300° C.
In still other embodiments, the surfactant mixture is removed through combination of acid extractions and ozonolysis treatments.
In certain embodiments, each layer of porous shell material is applied using alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof: comprising the steps of:
In some such embodiments, the alkoxysilane used is selected from the group of tetramethoxsilane or tetraethoxysilane.
In other such embodiments, the organosiloxane is selected as one or more of the following from the group of phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane, diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; or 1,3-bis(trimethoxysilylethyl)benzene, octadecyltrimethoxysilane, octadecyltriethoxysilane, octyltrimethoxysilane, octyltriethoxysilane, dodecyltrimethoxysilane, and dodecyltriethoxysilane.
In still other such embodiments, the alkoxysilane used is tetraethoxysilane and the organoalkoxysilane used is octadecyltrimethoxysilane.
In certain such embodiments, the alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are prediluted in ethanol.
In some such embodiments, the prediluted ethanol solutions of alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are added a slow and constant rate to prevent fines generation, aggregation and agglomeration.
In other such embodiments, prediluted ethanol solutions of alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are added a rate between 5-500 μL/min.
In certain embodiments, a secondary solution comprising ethanol, water, and ammonium hydroxide is added at a slow and constant rate to prevent fines generation, aggregation and agglomeration.
In certain other embodiments, a secondary solution comprising ethanol, water, and ammonium hydroxide is added within a range between the rate required to maintain a uniform ratio of particle surface area (m2) to reaction volume, to the rate required to maintain a uniform ratio of particle volume (m3) to reaction volume.
In certain embodiments, porosity is introduced through extraction, degradation, hydrolysis, deprotection, or transformation of the hybrid group through one or more of the following; extractions with acid, water, or organic solvent; ozonolysis treatments, thermal treatments<600° C., or thermal treatments between 500-1300° C.
In still other embodiments, porosity is introduced through extraction, degradation, hydrolysis, deprotection, or transformation of the hybrid group through combination of acid extractions, ozonolysis treatments and/or thermal treatments<600° C.
In certain embodiments, each layer is applied using a mixture of formula XX.
(D)d(E)e(F)f (Formula XX)
In certain such embodiments, the precursor for the inorganic component upon initial condensation (D) is selected from oxide, hydroxide, ethoxide, methoxide, propoxide, isopropoxide, butoxide, sec-butoxide, tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide, 2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate, nitrate, chlorides, and mixtures thereof of silicon, titanium, zirconium, or aluminum.
In other such embodiments, the precursor for the inorganic component upon initial condensation (D) is selected from tetraethoxysilane, tetramethoxysilane, methyl titanium triisopropoxide, methyl titanium triphenoxide, titanium allylacetoacetatetriisopropoxide, titanium methacrylate triisopropoxide, titanium methacryloxyethylacetoacetate triisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide, pentamethylcyclopentadienyl titanium trichloride, and zirconium methacryloxyethylacetoacetate tri-n-propoxide.
In still other such embodiments, the precursor for the hybrid component upon initial condensation (E) is selected from 1,2-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane, 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane.
In yet other such embodiments, the precursor for the hybrid component upon initial condensation that can be further reacted to increase the porosity of the superficially porous layer (F) is selected from phenyltrimethoxysilane, phenyltriethoxysilane, acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane; chlomethyltriethoxysilane; chloroethyltrimethoxysilane; methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane; bromoethyltrimethoxysilane; bromoethyltriethoxysilane; fluorotriethoxysilane; fluorotrimethoxysilane; and alkoxysilanes of the type:
(CH3CH2O)4-vSi(OR*)v (Formula XXb)
wherein
In such embodiments, porosity is introduced by reaction of hybrid group F through protodesilylation, hydrolysis, deprotection, acid extraction, thermal treatment<500° C., oxidation, ozonolysis or decomposition.
Another aspect of the invention provides a method to produce a core with increased hybrid content near the surface of the core by modifying a nonporous silica core with one more or more layers formed using an organosiloxane, a mixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybrid inorganic/organic core-coating material, or combination thereof.
Still another aspect of the invention provides a method to produce a superficially porous hybrid material that has increased hybrid content near the external surface of the material by modifying a superficially porous material with one more or more layers formed using an organosiloxane, a mixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybrid inorganic/organic core-coating material, or combination thereof.
Yet another aspect of the invention provides a method to produce a superficially porous hybrid particle that has increased hybrid content near the external surface of the particle by modifying a superficially porous particle with one more or more layers formed using an organosiloxane, a mixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybrid inorganic/organic core-coating material, or combination thereof.
Still another aspect of the invention provides a method to produce a superficially porous hybrid particle that has increased hybrid content near the external surface of the particle by modifying a superficially porous particle that is substantially silica (>90 molar %) with one more or more layers formed using an organosiloxane, a mixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybrid inorganic/organic core-coating material, or combination thereof.
Still yet another aspect of the invention provides a method to produce a superficially porous hybrid particle that has increased hybrid content near the external surface of the particle comprising the steps of
In certain embodiments of the invention, the methods provide materials in which 1-15 layers are formed in the process. In other aspects, 2-5 layers are formed. In still other 1-2 layers are formed.
In certain embodiments of the invention the superficially porous material is optimized by acid extraction, classification, ozonolysis treatment, hydrothermal treatment, acid treatment or combinations thereof.
In yet other embodiments of the invention, the superficially porous material is further surface modified. In some aspects by coating with a polymer; coating with a polymer by a combination of organic group and silanol group modification; a combination of organic group modification and coating with a polymer; a combination of silanol group modification and coating with a polymer; formation of an organic covalent bond between the material's organic group and a modifying reagent; or a combination of organic group modification, silanol group modification and coating with a polymer.
In another aspect, the invention provides a method for increasing the porosity of a substantially nonporous material comprising:
In such methods of increasing the porosity of a substantially nonporous material, the methods of applying to said core material one or more layers of porous shell material will be understood to be substantially the same as those described above for preparing a superficially porous material and should be considered as such.
The invention also provides methods for producing the inorganic/organic hybrid materials described herein.
In one embodiment, the invention provides a method for producing the inorganic/organic hybrid materials described herein comprising:
In another embodiment, the invention provides a method for producing the inorganic/organic hybrid materials described herein comprising:
In certain embodiments, the method producing the inorganic/organic hybrid materials described herein further comprises the step of subjecting the hybrid material to hydrothermal treatment.
In another embodiment, the invention provides a method for producing the inorganic/organic hybrid materials described herein, comprising the steps of:
In another embodiment, the invention provides a method for producing the inorganic/organic hybrid materials described herein comprising the steps of:
In certain embodiments, the process of producing the inorganic/organic hybrid materials described herein as described above further comprises the step of subjecting the hybrid material to hydrothermal treatment.
In certain embodiments, following hydrothermal treatment, the surfaces of the coated cores and/or the materials are modified with various agents. Such “surface modifiers” include (typically) organic functional groups which impart a certain chromatographic functionality to a chromatographic stationary phase. The porous inorganic/organic hybrid particles possess both organic groups and silanol groups which may additionally be substituted or derivatized with a surface modifier.
In some embodiments, the surface of the hydrothermally treated coated cores and/or core-coating material materials contains organic groups, which can be derivatized by reacting with a reagent that is reactive towards the particles' organic group. For example, vinyl groups on the particle can be reacted with a variety of olefin reactive reagents such as bromine (Br2), hydrogen (H2), free radicals, propagating polymer radical centers, dienes and the like. In another example, hydroxyl groups on the particle can be reacted with a variety of alcohol reactive reagents such as isocyanates, carboxylic acids, carboxylic acid chlorides and reactive organosilanes as described below. Reactions of this type are well known in the literature, see, e.g., March, J. Advanced Organic Chemistry, 3rd Edition, Wiley, New York, 1985; Odian, G. The Principles of Polymerization, 2nd Edition, Wiley, New York, 1981.
In additional embodiments, the surface of the hydrothermally treated coated cores and/or core-coating material materials also contains silanol groups, which can be derivatized by reacting with a reactive organosilane. The surface derivatization of the coated cores and/or core-coating material materials is conducted according to standard methods, for example by reaction with octadecyltrichlorosilane or octadecyldimethylchlorosilane in an organic solvent under reflux conditions. An organic solvent such as toluene is typically used for this reaction. An organic base such as pyridine or imidazole is added to the reaction mixture to catalyze the reaction. The product of this reaction is then washed with water, toluene and acetone and dried at 80° C. to 100° C. under reduced pressure for 16 h. The resultant hybrid particles can be further reacted with a short-chain silane such as trimethylchlorosilane to endcap the remaining silanol groups, by using a similar procedure described above.
In other embodiments, surface modifiers such as disclosed herein are attached to the base material, e.g., via derivatization or coating and later crosslinking, imparting the chemical character of the surface modifier to the base material. In one embodiment, the organic groups of the coated cores and/or core-coating material materials react to form an organic covalent bond with a surface modifier. The modifiers can form an organic covalent bond to the particle's organic group via number of mechanisms well known in organic and polymer chemistry including but not limited to nucleophilic, electrophilic, cycloaddition, free-radical, carbene, nitrene and carbocation reactions. Organic covalent bonds are defined to involve the formation of a covalent bond between the common elements of organic chemistry including but not limited to hydrogen, boron, carbon, nitrogen, oxygen, silicon, phosphorus, sulfur and the halogens. In addition, carbon-silicon and carbon-oxygen-silicon bonds are defined as organic covalent bonds, whereas silicon-oxygen-silicon bonds that are not defined as organic covalent bonds.
The term “functionalizing group” includes organic functional groups which impart a certain chromatographic functionality to a chromatographic stationary phase, including, e.g., octadecyl (C18) or phenyl. Such functionalizing groups are incorporated into base material directly, or present in, e.g., surface modifiers such as disclosed herein which are attached to the base material, e.g., via derivatization or coating and later crosslinking, imparting the chemical character of the surface modifier to the base material.
In certain embodiments, silanol groups are surface modified. In other embodiments, organic groups are surface modified. In still other embodiments, the coated cores' and/or core-coating material materials' organic groups and silanol groups are both surface modified or derivatized. In another embodiment, the particles are surface modified by coating with a polymer. In certain embodiments, surface modification by coating with a polymer is used in conjunction with silanol group modification, organic group modification, or both silanol and organic group modification.
More generally, the surface of coated cores and/or the superficially porous materials of the invention may be modified by: treatment with surface modifiers including compounds of formula Za(R′)bSi—R″, where Z═Cl, Br, I, C1-C5 alkoxy, dialkylamino, e.g., dimethylamino, or trifluoromethanesulfonate; a and b are each an integer from 0 to 3 provided that a+b=3; R′ is a C1-C6 straight, cyclic or branched alkyl group, and R″ is a functionalizing group. In certain instances, such particles have been surface modified by coating with a polymer.
R′ includes, e.g., methyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl, isopentyl, hexyl or cyclohexyl; preferably, R′ is methyl.
The functionalizing group R″ may include alkyl, alkenyl, alkynyl, aryl, cyano, amino, diol, nitro, ester, cation or anion exchange groups, an alkyl or aryl group containing an embedded polar functionalities or chiral moieties. Examples of suitable R″ functionalizing groups include chiral moieties, C1-C30 alkyl, including C1-C20, such as octyl (C8), octadecyl (C18) and triacontyl (C30); alkaryl, e.g., C1-C4-phenyl; cyanoalkyl groups, e.g., cyanopropyl; diol groups, e.g., propyldiol; amino groups, e.g., aminopropyl; and alkyl or aryl groups with embedded polar functionalities, e.g., carbamate functionalities such as disclosed in U.S. Pat. No. 5,374,755, and chiral moieties. Such groups include those of the general formula
wherein l, m, o, r and s are 0 or 1, n is 0, 1, 2 or 3 p is 0, 1, 2, 3 or 4 and q is an integer from 0 to 19; R3 is selected from the group consisting of hydrogen, alkyl, cyano and phenyl; and Z, R′, a and b are defined as above. Preferably, the carbamate functionality has the general structure indicated below:
wherein R5 may be, e.g., cyanoalkyl, t-butyl, butyl, octyl, dodecyl, tetradecyl, octadecyl, or benzyl. Advantageously, R5 is octyl, dodecyl, or octadecyl.
In certain applications, such as chiral separations, the inclusion of a chiral moiety as a functionalizing group is particularly advantageous.
Polymer coatings are known in the literature and may be provided generally by polymerization or polycondensation of physisorbed monomers onto the surface without chemical bonding of the polymer layer to the support (type I), polymerization or polycondensation of physisorbed monomers onto the surface with chemical bonding of the polymer layer to the support (type II), immobilization of physisorbed prepolymers to the support (type III) and chemisorption of presynthesized polymers onto the surface of the support (type IV). see, e.g., Hanson, et al., J. Chromat. A656 (1993) 369-380, the text of which is incorporated herein by reference. As noted above, coating the hybrid material with a polymer may be used in conjunction with various surface modifications described in the invention.
Thus, in certain embodiments, the surface modifier is selected from the group consisting of octyltrichlorosilane, octadecyltrichlorosilane, octyldimethylchlorosilane and octadecyldimethylchlorosilane. In a further embodiment, the surface modifier is selected from the group consisting of octyltrichlorosilane and octadecyltrichlorosilane.
In another embodiment, the coated cores and/or the superficially porous materials of the invention have been surface modified by a combination of organic group and silanol group modification.
In other embodiments, the coated cores and/or the superficially porous materials of the invention have been surface modified by a combination of organic group modification and coating with a polymer.
In other embodiments, the coated cores and/or the superficially porous materials of the invention have been surface modified by a combination of silanol group modification and coating with a polymer.
In another embodiment, the coated cores and/or the superficially porous materials of the invention have been surface modified via formation of an organic covalent bond between the coated cores' and/or core-coating material materials' organic group and the modifying reagent.
In certain embodiments, the coated cores and/or the superficially porous materials of the invention have been surface modified by a combination of organic group modification, silanol group modification and coating with a polymer.
In one embodiment, the coated cores and/or the superficially porous materials of the invention have been surface modified by silanol group modification.
In another embodiment, the invention provides a method wherein the coated cores and/or the superficially porous materials of the invention are modified by further including a porogen. In a further embodiment, the porogen is selected from the group consisting of cyclohexanol, toluene, mesitylene, 2-ethylhexanoic acid, dibutylphthalate, 1-methyl-2-pyrrolidinone, 1-dodecanol and Triton X-45. In certain embodiments, the porogen is toluene or mesitylene.
In one embodiment, the invention provides a method wherein the coated cores and/or the superficially porous materials of the invention are further modified by including a surfactant or stabilizer. In certain embodiments, the surfactant is Triton X-45, Triton X100, Triton X305, TLS, Pluronic F-87, Pluronic P-105, Pluronic P-123, sodium dodecylsulfate (SDS), ammonia docecylsulfate, TRIS docecylsulfate, or Triton X-165. In certain embodiments, the surfactant is sodium dodecylsulfate (SDS), ammonia docecylsulfate, or TRIS docecylsulfate.
Certain embodiments of the synthesis of the cores and/or the superficially porous materials of the invention described above are further illustrated in the Examples below.
In certain embodiments, the core material is subjected to a thermal treatment in air prior to the application of the coating material. In such embodiments, the core materials are thermally treated in air or in an inert atmosphere (e.g., nitrogen) at temperatures ranging from 600-1300° C., more specifically 800-1250° C., more specifically 900-1300° C.
In still other embodiments, the coated cores and/or the superficially porous materials of the invention are subject to a thermal treatment before or after application of the surrounding material In such embodiments, the materials are thermally treated in air or in an inert atmosphere (e.g., nitrogen) at temperatures ranging from 600-1300° C., more specifically 800-1250° C., more specifically 900-1300° C. Particles can be thermally treated at these temperatures between layers of sols during superficially porous synthesis and/or on the final layer with or without the application of a surrounding material between layers or on the final layer.
Another aspect provides a variety of separations devices having a stationary phase comprising the materials as described herein. The separations devices include, e.g., chromatographic columns, thin layer plates, filtration membranes, sample cleanup devices and microtiter plates; packings for HPLC columns; solid phase extraction (SPE); ion-exchange chromatography; magnetic bead applications; affinity chromatographic and SPE sorbents; sequestering reagents; solid supports for combinatorial chemistry; solid supports for oligosaccharide, polypeptides, and/or oligonucleotide synthesis; solid supported biological assays; capillary biological assay devices for mass spectrometry, templates for controlled large pore polymer films; capillary chromatography; electrokinetic pump packing materials; packing materials for microfluidic devices; polymer additives; catalysis supports; and packings materials for microchip separation devices. Similarly, materials of the invention can be packed into prepartory, microbore, capillary, and microfluidic devices.
The materials of the invention impart to these devices improved lifetimes because of theirimproved stability. Thus, in a particular aspect, the invention provides a chromatographic column having improved lifetime, comprising
The invention also provides for a kit comprising the materials as described herein, as described herein, and instructions for use. In one embodiment, the instructions are for use with a separations device, e.g., chromatographic columns, thin layer plates, filtration membranes, sample cleanup devices, solid phase extraction device, microfluidic device, and microtiter plates.
The present invention may be further illustrated by the following non-limiting examples describing the chromatographic materials.
As described herein, this invention relates to the use of surface modified superficially porous particles as a stationary phase for chromatographic separations under high pH conditions. Until recently, commercially available superficially porous products were comprised of silica particles, which were not suited for high pH separations due to the dissolution of silica at pH values above 7. Modifying the surface of superficially porous particles with organic/inorganic hybrid polyethoxyoligosiloxane polymer (PEOS), in the presence of water, results in a product that successfully extends column stability at higher pH values (10-12). While a significant improvement over non-surface modified superficially porous particles (i.e., 100% silica) was observed, these columns were not as stable as fully porous organic/inorganic hybrid patticles. To determine the cause of column failure, the surface modified superficially porous particles were analyzed after testing under high pH conditions (10 mM Ammonium Bicarbonate, pH 10.5, 60° C.). SEM images of the unpacked material did not show significant changes compared to the same material before it was tested (
Core Erosion was later confirmed with cross-sectional images of these surface modified superficially porous particles (
The erosion of core particles leads to a mechanically unstable column that will result in bed collapse, causing large voids at the head of the column and frit clogging at the end of the column; this will be observed by a considerable increase in column backpressure as well as poor analyte peak shapes. The aforementioned physical observations and chromatographic effects are observed when these columns are tested under high pH conditions (10 mM Ammonium Bicarbonate, pH 10.5, 60° C.). In addition, a significant particle size effect is observed with respect to failure under high pH conditions—as particle size decreases, the high pH stability of the columns packed with that material considerably decreases (
Test 1) Mobile Phase Gradient: 5% to 95% B in 2.3 minutes using a linear curve; 0.7 minute hold at 95% B; return to initial conditions and hold for 1.5 minutes (A=10 mM Ammonium Bicarbonate, pH 10.5 and B=100% Acetonitrile) at a flow rate of 0.8 mL/minute. The 2.1×50 mm column is kept at a constant temperature of 60° C. The standard injection volume is 3 μL. In this test, a material is considered base stable if it exhibits none of the performance or attribute changes listed above before 500-3000 injections;
Test 2) Mobile phase: 10 mM Ammonium Bicarbonate (pH 10.5) isocratic at a constant flow rate of 0.21 mL/min. The 2.1×50 mm column is kept at a constant temperature of 70° C. A material is considered base stable if it retains more than 60-80% of stationary mass after 36 hours.
All reagents were used as received unless otherwise noted. Those skilled in the art will recognize that equivalents of the following supplies and suppliers exist and, as such, the suppliers listed below are not to be construed as limiting.
Those skilled in the art will recognize that equivalents of the following instruments and suppliers exist and, as such, the instruments listed below are not to be construed as limiting.
The % C, % H, % N values were measured by combustion analysis (CE-440 Elemental Analyzer; Exeter Analytical Inc., North Chelmsford, MA) or % C by Coulometric Carbon Analyzer (modules CM5300, CM5014, UIC Inc., Joliet, IL). The specific surface areas (SSA), specific pore volumes (SPV) and the average pore diameters (APD) of these materials were measured using the multi-point N2 sorption method (Micromeritics ASAP 2400; Micromeritics Instruments Inc., Norcross, GA). The SSA was calculated using the BET method, the SPV was the single point value determined for P/P0>0.98 and the APD was calculated from the desorption leg of the isotherm using the BJH method. The median mesopore diameter (MPD) and mesopore pore volume (MPV) were measured by mercury porosimetry (Micromeritics AutoPore IV, Micromeritics, Norcross, GA). Scanning electron microscopic (SEM) image analyses were performed (JEOL JSM-5600 instrument, Tokyo, Japan or Hitachi SU8030 instrument, Dallas, TX) at 1-7 kV. Focused ion beam scanning electron microscopic (FIB/SEM) image analyses were performed by Analytical Answers Inc. (Woburn, MA) on an FEI Model 200 Focused Ion Beam instrument, and a Hitachi S4800 Ultra-Field emission SEM. Particle sizes were measured using a Beckman Coulter Multisizer 3 analyzer (30 μm aperture, 70,000 counts; Miami, FL) or manually using SEM. Particles were prepared for cross-sectional imaging using a broad ion beam milling system (Hitachi IM 4000 plus). The particle diameter (dp) was measured by SEM or by using a Beckman Coulter as the 50% cumulative diameter of the volume based particle size distribution or mode of the number based particle size distribution. The width of the distribution was measured as the 90% cumulative volume diameter divided by the 10% cumulative volume diameter (denoted 90/10 ratio). Metals content was measured by ICP-AE (Thermo Fisher Scientific iCAP 6500 Duo). Light scattering particle size measurements were measured using a Malvern Mastersizer 2000 in water. Particle size measurements of nanoparticles and Zeta-potential measurements were made using a Malvern ZetaSizer NanoSeries (model ZEN3600). Multinuclear (13C, 29Si) CP-MAS NMR spectra were obtained using a Bruker Instruments Avance-300 spectrometer (7 mm double broadband probe). The spinning speed was typically 5.0-6.5 kHz, recycle delay was 5 sec. and the cross-polarization contact time was 6 msec. Reported 13C and 29Si CP-MAS NMR spectral shifts were recorded relative to tetramethylsilane using the external standards adamantane (13C CP-MAS NMR, δ 38.55) and hexamethylcyclotrisiloxane (29Si CP-MAS NMR, δ −9.62). Populations of different silicon environments were evaluated by spectral deconvolution using DMFit software. [Massiot, D.; Fayon, F.; Capron, M.; King, I.; Le Calvé, S.; Alonso, B.; Durand, J.-O.; Bujoli, B.; Gan, Z.; Hoatson, G. Magn. Reson. Chem. 2002, 40, 70-76]. Classification techniques are described, for example, in W. Gerhartz, et al. (editors) Ullmann's Encyclopedia of Industrial Chemistry, 5th edition, Volume B2: Unit Operations I, VCH Verlagsgesellschaft mbH, (Weinheim, Fed. Rep. Germ. 1988). Magnetic measurements were made using a vibrating sample magnetometer (ADE/DMS Model 880) by ArKival Technology Corporation (Nashua, NH). Phase characterization were made by Wide Angle X-Ray Powder Diffraction (XRPD) analysis (H&M Analytical Services, Inc. Allentown, N.J.), using a Bruker D4 diffractometer (Cu radiation at 40 KV/30 mA). Scans were run over the angular range of 10° to 90° 2-Theta with a step size of 0.02° and a counting time of 715 seconds per step.
Non-porous silica particles, as received, were heat treated (900° C.) in air for 10 h. The surface of the particles were rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried at 80° C. under 25 mm vacuum. This process of treating NPS cores is used often in the subsequent examples. It can be referred to as “control cores”.
Control cores from Example CC-1 were fully dispersed in toluene (10 mL/g) Then azeotropically stripped (111° C., 2.5 h) to ensure anhydrous conditions. Zirconium propoxide (70% in propanol; 2 μmol/m2) was diluted in an equal mass of toluene, added to the NPS/toluene slurry, then stirred at RT for 1 h. The slurry was then allowed to stir at reflux for 16 h under an inert atmosphere. The reaction was then cooled to RT and the particles were isolated via filtration. The particles were subsequently washed (10 ml/g) using the following sequence: 3× toluene, 3× formic acid (aqueous; 1% w/w), 7× water, 1× acetone/water (1:1 v/v), 2× acetone. Finally, the isolated, surface modified particles were dried for 16 h at 65° C. under 25 mm vacuum. Zirconium concentration was determined to be 793 ppm by ICP-AE. There was no noticeable particle size difference observed via SEM as compared to material before it was modified.
The surface modified particles from Example CC-2 were heat treated at 450° C. for 6 hours followed by 5 hours at 750° C. Zirconium concentration was determined to be 812 ppm by ICP-AE.
The surface modified particles from Example CC-2 were further modified by adding an additional layer of Zirconium following the process as described in Example CC-2 after the initial heat treatment. Zirconium concentration was determined to be 1667 ppm by ICP-AE. There was no noticeable particle size difference observed via SEM as compared to material before it was modified.
The surface modified particles from Example CC-4 were heat treated at 450° C. for 6 hours followed by 5 hours at 750° C. Zirconium concentration was determined to be 1682 ppm by ICP-AE.
The surface modified particles from Example CC-2 are further modified by repeating the process as described in Example CC-2, after the initial heat treatment and rehydroxylation, up to 60 times and/or to a total Zirconium thickness of 100 nm.
The surface modified particles from Example CC-6 are heat treated at 450° C. for 6 hours followed by 5 hours at 750° C.-1300° C.
Control cores from Example CC-1 were fully dispersed in toluene (18 mL/g) then azeotropically stripped (111° C., 1 h) to remove residual water from the material. These initial anhydrous conditions are important as they ensure water content accuracy when water is added in the subsequent step. The reaction temperature was held at 40° C. while 100% 1,2-bis(triethoxylsilyl)ethane (BTEE) PEOS (0.821 g PEOS/g NPS) was added and allowed to stir for 10 minutes followed by water in the form of an acid or base catalyst, in this case, NH4OH(aq) (0.1 g base/g NPS). The reaction was stirred for an additional 10 minutes at 40° C. before the temperature was increased to 60° C. for 2 h. The reaction was then cooled to RT and the particles were isolated via filtration. The particles were subsequently washed twice with ethanol (10 ml/g) then redispersed in 70/30 (v/v) water/ethanol (10 mL/g). Ammonium Hydroxide (1 g NH4OH/g NPS) was then added and the mixture was stirred at 50° C. for 2 h. The reaction was then cooled<40° C. and the particles were isolated via filtration. The isolated particles were washed (10 ml/g) using the following sequence: 2× methanol/water (1:1 v/v), 2× methanol. Finally, the isolated, surface modified particles were dried for 16 h at 80° C. under 25 mm vacuum. Carbon content was determined to be 435 ppm by Coulometric Carbon Analyzer.
Nonporous silica particles (10.4 g, 1.26 μm), that were previously thermally treated at 600° C. (10 h) and rehydroxylated using 10% nitric acid (Fisher scientific), were dispersed in 100 mL of solvent (water:anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes. Separately, octadecyltrimethylammonium bromide (2.46 g, C18TAB, Sigma-Aldrich) was dissolved in 100 mL of solvent (water:anhydrous ethanol 2:1 v/v). The C18TAB solution was then added into the particle solution and was sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of Pluronic P123 (39.0 g, Sigma-Aldrich) was dissolved in 400 mL of solvent (water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B (400 mL) was added into solution A (200 mL) and allowed to continue sonicate for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and stirred at 750 rpm Ammonium hydroxide solution (30%, 24 mL, J. T. Baker) was added into the flask and allowed to continue stirring for 5 minutes. 1,2-bis(triethoxysilyl)ethane (6 ml, BTEE, Gelest) was first diluted with anhydrous ethanol (dilution factor=3) and then added to the flask with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at a constant flow rate (50 μL/min). The reaction was allowed to continue stirring until all BTEE was added, allowed to stir for an extra hour before washing. The coating thickness was controlled by the amount of BTEE added to the reaction. The final concentrations reagents used were C18TAB (2.6-17.27 mM), Pluronic P123 (3.5-22.16 mM), and BTEE (0.020-0.030 M). During the washing step, the sample was diluted four times the sample volume with deionized water, followed by centrifugation (Forma Scientific Model 5681, 2,500 rpm, 6 min). The wash sequence was repeated two times using sonication to redisperse particles. The growth process was done once to grow a hybrid layer on the nonporous silica core. Products were isolated by centrifugation and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.) The particles were then dispersed in 2 M solution of hydrochloric acid in acetone, at room temperatures (30° C.). The mixture was mechanically stirred for 18 hours. Products were isolated by centrifugation (Forma Scientific Model 5681, 4000 rpm, 10 min) followed by 4 washes with DI water (or until pH is greater than 6) and 2 washes with methanol using sonication to redisperse particles. Products were dried at 80° C. under vacuum for 16 hours and submitted for, SEM, and nitrogen sorption analysis.
The process as described in Example CC-8 and CC-8a, after the initial heat treatment and rehydroxylation, is further expanded to include monomer and polymer inorganic and/or organic materials in place of 100% BTEE PEOS, as noted in patents [US 2014031905, 20150133294, 20150136700, 20130319086, 20130273404, 20130112605, 20130206665, 2012055860, 20110049056, 20120141789, 20140194283, 20090209722, 20100076103, as well as U.S. Pat. Nos. 9,248,383, 9,145,481, 9,120,083, 8,778,453, 8,658,277, 7,919,177, 7,223,473, 6,686,035] up to 60 times and/or to a total core-coating material thickness of 200 nm.
Non-porous silica particles, as received, were heat treated (1090° C.) in air for 24 h. While not limited by theory, the increased temperature and time at temperature should allow for further densification of the silica core resulting in increased stability under high pH conditions. A significant degree of agglomerated particles were present after thermal treatment; this may be reduced by adding dispersants prior to thermal treatment.
The modified core particles from Experiments CC-1, CC-2, CC-8, and CC-10, were subjected to elevated temperatures (100 and 140° C.) and pH (9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. Stability for these experiments was determined by evidence of silica dissolution via change in particle size (n, mode; Coulter) and SEM morphology (surface holes and indentations) compared to the starting material. A summary of these experiments can be viewed in Table CC-1.
Results indicate none of the hydrothermally treated, core modified materials show evidence of core erosion at 100° C. or 140° C. Some morphology differences (surface indentations) were visible on the SEM images of the NPS material that was calcined at 1090° C. then hydrothermally treated. While not limited by theory, it is believed that these indentations are not due to silica dissolution; instead they are due to particles agglomerating together during thermal treatment at the extreme temperature then breaking apart during the sonication step before hydrothermal treatment, exposing non-spherical areas where the particles were once connected. It was therefore concluded that the surface modified cores resulted in no measureable high pH stability difference compared to the starting, non-modified, NPS under these conditions. Surprisingly, the non-modified NPS, control product (Sample 1) did not show evidence of dissolution after hydrothermal treatment at 100° C. or 140° C., Samples 1a and 1 b; respectively, either. The level of defects observed in each of the hydrothermally treated materials was equivalent to the defect level of the starting NPS materials, thus no morphology differences were reported. The lack of morphology change could indicate uniform dissolution; since the experiments were performed in a closed system dissolved silicates were allowed to redeposit onto the silica surface. Therefore, while not limited by theory, morphology changes observed in cores (surface holes and indentations), may indicate non-uniform dissolution.
The surface modified NPS cores from Examples CC-1, CC-3, CC-5, CC-8, and CC-10 as well as 100% Zirconium cores were packed into a HPLC column (2.1×50 mm), dried (60° C., 30 in Hg), weighted, exposed to high pH conditions as described in “sample test 2” (10 mM Ammonium Bicarbonate, pH 10.5, 0.21 ml/min, 36 h), then re-dried and re-weighed. Results from this example can be found in Table CC-2. Stability for these experiments was determined by evidence of silica dissolution via SEM morphology (surface holes, texture, and indentations) as well as change in particle size (n, mode; Coulter), column weight loss (%), and column bed loss (%), compared to the starting material. Not limited by theory, it is believed that any dissolved silicates would continue to travel with the mobile phase out of the column with minimal, if any, re-deposition of silica onto the surface of the NPS under the aforementioned testing conditions.
While significant silica dissolution was expected for the control (Sample 1), it was surprising that the BTEE surface modified product (Sample 8), and zirconium modified products (Samples 3 and 5) did not show an improvement over the control; all resulted in similar column weight losses and column bed voids of approximately 51% for both metrics. However, SEM images of the surface modified materials (
The sample that was exposed to a higher thermal temperature (Sample 10) resulted in significantly less weight loss as compared to the control (Sample 1; 31% vs. 51%). Smooth particle surfaces, similar to the starting material, were observed in SEM images of this product (
The 100% zirconium product (Sample 0) showed no signs of core erosion as determined by a 0% weight loss and 1% column void after 36 hours of testing under these high pH conditions.
Non-porous silica particles, as received, are heat treated (900-1300° C.) in air for 10-24 h. The surface of the particles are rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the core is then modified using the process described below (
Heat treated NPS particles are fully dispersed in toluene (21 mL/g). An azeotropic strip (111° C., 1 h) is then performed to remove residual water from the material. These initial anhydrous conditions are important as they ensure water content accuracy when water is added in the subsequent step. The reaction temperature is held at 40° C. while 100% BTEE PEOS (0.821 g PEOS/g cores) is added and allowed to stir for 10 minutes followed by water in the form of a catalyst (0.03-0.1 g acid or base/g cores). The reaction is stirred for an additional 10 minutes at 40° C. before the temperature is increased to 60° C. for 2 h. The reaction is then cooled to RT and the particles are isolated via filtration. The particles are subsequently washed twice with ethanol (10 ml/g) then redispersed in 70/30 (v/v) water/ethanol (10 mL/g). Ammonium Hydroxide (1 g NH4OH/g cores) is added and the mixture is stirred at 50° C. for 2 h. The reaction is then cooled<40° C. and the particles are isolated via filtration. The isolated particles are washed (10 ml/g) using the following sequence: 2× methanol/water (1:1 v/v), 2× methanol. Finally, the isolated, surface modified particles are dried for 16 h at 80° C. under 25 mm vacuum. The above process is repeated a 1-60 times.
To ensure uniformity of the hybrid layer produced above, the modified particles are exposed to elevated temperatures (100-140° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. The process of attaching 100% BTEE PEOS core-coating material, as described above, is repeated 1-60 additional times. The surface modified particles are again exposed to elevated temperatures (100-140° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.
The surface hybridized particles are then refluxed in 1M HCl (8.4 mL/g) for 20 hours. The reaction is then cooled to RT and the particles are isolated via filtration. The particles are washed with copious amounts of water until the pH is increased to >5. The semi-neutralized particles are then washed thrice with acetone (10 ml/g). The particles are then sized to remove any agglomerated and fine particles that may be present.
The process as described in Example CC-13 is further expanded to include monomer and polymer inorganic and/or organic materials in place of 100% BTEE PEOS, as noted in patents [US 2014031905, 20150133294, 20150136700, 20130319086, 20130273404, 20130112605, 20130206665, 2012055860, 20110049056, 20120141789, 20140194283, 20090209722, 20100076103 as well as U.S. Pat. Nos. 9,248,383, 9,145,481, 9,120,083, 8,778,453, 8,658,277, 7,919,177, 7,223,473, 6,686,035] and the surface modification process can be repeated up to 60 times.
The surface of the control core particles from Example CC-1 were then modified as described below.
Superficially porous silica layers can be formed on nonporous silica core material, by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf. Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols){Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 8-12 layers of the same size nanoparticles were used.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte was removed by thermal treatment in air (540° C.) for 20 hours. To further strengthen these materials, a second thermal treatment (900° C.) was employed for 20 hours. A rehydroxylation step was then performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particles were then modified with hybrid using the process below:
The superficially porous particles were fully dispersed in toluene (21 mL/g). An azeotropic strip (111° C., 1 h) was then performed to remove residual water from the material. These initial anhydrous conditions are important as they ensure water content accuracy when water is added in the subsequent step. The reaction temperature was held at 40° C. while 100% BTEE PEOS (0.821 g PEOS/g particle) was added and allowed to stir for 10 minutes followed by water in the form of a catalyst, in this case NH4OH(aq) (0.03-0.1 g base/g particle). The reaction was stirred for an additional 10 minutes at 40° C. before the temperature was increased to 60° C. for 2 h. The reaction was then cooled to RT and the particles were isolated via filtration. The particles were subsequently washed twice with ethanol (10 ml/g) then redispersed in 70/30 (v/v) water/ethanol (10 mL/g). Ammonium Hydroxide (1 g NH4OH/g particle) was added and the mixture was stirred at 50° C. for 2 h. The reaction was then cooled<40° C. and the particles were isolated via filtration. The isolated particles were washed (10 ml/g) using the following sequence: 2× methanol/water (1:1 v/v), 2× methanol. Finally, the isolated, surface modified particles were dried for 16 h at 80° C. under 25 mm vacuum. The above process was repeated a second time.
To ensure uniformity of the hybrid layer produced above, the modified particles were exposed to elevated temperatures (100-155° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. The process of attaching 100% BTEE PEOS core-coating material, as described above, was repeated one additional time for a 2.7 μm particle and two additional times for a 1.6 μm particle. The surface modified particles were again exposed to elevated temperatures (100-155° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.
The hybrid surface modified superficially porous particles were then refluxed in 1M HCl (8.4 mL/g) for 20 hours. The reaction was then cooled to RT and the particles were isolated via filtration. The particles were washed with copious amounts of water until the pH was increased to >5. The semi-neutralized particles were then washed thrice with acetone (10 ml/g). The particles were sized to remove any agglomerates that may have been present. The surface of the particles were then bonded with tC18
Non-porous silica particles, as received, are heat treated (900-1300° C.) in air for 10-24 h. The surface of the particles are rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the particles are then modified as described below.
Superficially porous silica layers can be formed on nonporous silica core material, by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols) {Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 8-20 layers of the same size nanoparticles are used.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte is removed by thermal treatment in air (540° C.) for 20 hours. To further strengthen these materials, a second thermal treatment (900° C.) is employed for 20 hours. A rehydroxylation step is then performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particles are then modified with hybrid using the process below:
The superficially porous particles are fully dispersed in toluene (21 mL/g). An azeotropic strip (111° C., 1 h) is then performed to remove residual water from the material. These initial anhydrous conditions are important as they ensure water content accuracy when water is added in the subsequent step. The reaction temperature is held at 40° C. while 100% BTEE PEOS (0.821 g PEOS/g particle) is added and allowed to stir for 10 minutes followed by water in the form of an acid or base catalyst (0.03-0.1 g acid or base/g particle). The reaction is stirred for an additional 10 minutes at 40° C. before the temperature is increased to 60° C. for 2 h. The reaction is then cooled to RT and the particles are isolated via filtration. The particles are subsequently washed twice with ethanol (10 ml/g) then redispersed in 70130 (v/v) water/ethanol (10 mL/g). Ammonium Hydroxide (1 g NH4OH/g particle) is added and the mixture is stirred at 50° C. for 2 h. The reaction is then cooled<40° C. and the particles are isolated via filtration. The isolated particles are washed (10 ml/g) using the following sequence: 2× methanol/water (1:1 v/v), 2× methanol. Finally, the isolated, surface modified particles are dried for 16 h at 80° C. under 25 mm vacuum. The above process is repeated 2-60 times.
To ensure uniformity of the hybrid layer produced above, the modified particles are exposed to elevated temperatures (100-155° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. The process of attaching 100% BTEE PEOS core-coating material, as described above, is repeated 1-60 additional times. The surface modified particles are again exposed to elevated temperatures (100-155° C.) and pH (8-9.8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.
The hybrid surface modified superficially porous particles are then refluxed in 1M HCl (8.4 mL/g) for 20 hours. The reaction is then cooled to RT and the particles are isolated via filtration. The particles are washed with copious amounts of water until the pH was increased to >5. The semi-neutralized particles are then washed thrice with acetone (10 ml/g). The particles are then sized to remove any agglomerates that may be present.
The process as described in Example CC-16 is further expanded to include monomer and polymer inorganic and/or organic materials in place of or in addition to 100% BTEE PEOS, as noted in patents [US 2014031905, 20150133294, 20150136700, 20130319086, 20130273404, 20130112605, 20130206665, 2012055860, 20110049056, 20120141789, 20140194283, 20090209722, 20100076103 as well as U.S. Pat. Nos. 9,248,383, 9,145,481, 9,120,083, 8,778,453, 8,658,277, 7,919,177, 7,223,473, 6,686,035].
The surface modified superficially porous particles from Example CC-15 were packed into HPLC columns (2.1×50 mm) and tested for stability under high pH conditions (10 mM Ammonium Bicarbonate, pH 10.5, 60° C.) using the mobile phase gradient as described in “sample test 1”.
While not limited by theory, bumpy cores increase the surface area around the core; this allows for more surface on which to build the initial hybrid layer. More significantly, it changes the curvature of the core.
An unmodified core is highly spherical and has very low surface area. When the porous layer is applied, a new interface between the core surface and the porous layer is produced. Localized areas of this interface (e.g., 10-100 nm regions of this core/porous layer interface), as imaged by BIB-SEM or FIB-SEM, indicate three possible states that can be uniform or non-uniform across the remaining core/porous-layer interface of a single particle. This observation of uniformity or non-uniformity can also be observed as homogeneous or heterogeneous throughout for multiple particles in a BIB-SEM or FIB-SEM analysis. It is desirable to have uniform morphology at this interface both within a particle and for a plurality of particles. The disadvantages of poor morphology at this interface can result in both mechanical and chemical instability.
The three states of this core/porous-layer interface, as determined by BIB-SEM or FIB-SEM analysis, include; (State 1) direct contact of the porous layer (as observed as nanoparticle) with the particle core (
When a hybrid core-coating material is applied on these differing core/porous-layer interfaces, different results are expected. For the region of state 3, the core and porous layer have independent surfaces. The concern for this region is mechanical instability, potential failure or delamination of the core/porous-layer interface, or chemical instability. The porous layer has a similar state of curvature between any two nanoparticles, and is this curvature is significantly higher than the curvature of an unmodified core. For the region of state 1, it is inconclusive if there is a strong attachment between the core and porous-layer. As such, there are concerns of mechanical instability, potential failure or delamination of the core/porous-layer interface, or chemical instability. There are additional concerns of differing surface curvatures between the core and porous layer. The porous layer has a similar state of curvature between any two nanoparticles, and is this curvature is significantly higher than the curvature of an unmodified core. The nanoparticle that is situated at the core/porous-layer interface creates a unique surface curvature that is higher than the curvature experience between any two nanoparticle in the porous layer.
State 2 is preferred. The ways in which state 2 can be obtained are:
An example in which superficially porous particles were made using the same size sols as an initial layer combined with an aggressive hydrothermal treatment is described below.
Non-porous silica particles, as received, were heat treated (900° C.) in air for 10 h. The surface of the particles were rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the particles were then modified as described below.
Superficially porous silica layers are formed on nonporous silica core material, prepared by the general approach of Stuber {U.S. Pat. No. 3,634,558; J. Coll. Interf Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols){Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. The initial 2 layers were formed using 6 nm sols to create a bumpy surface.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte was removed by thermal treatment in air at 560° C. (10-20 hours). The bumpy particles were then exposed to elevated temperature (100° C.) and pH (8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177}. The layer-by-layer approach as described above was continued using the same sized sols (6 nm) until a total of 8 layers were deposited on the surface of the core. The polyelectrolye was removed using the same thermal treatment as described above followed by a second thermal treatment at 900° C. for 10-20 hours. A rehydroxylation step was performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particle was then modified with a hybrid layer using the surface modification processes employed in Examples CC-15, CC-16, or CC-17.
Following the reasoning from Example CC-19, an example in which superficially porous particles were made using different size sols as an initial layer combined with an aggressive hydrothermal treatment is described below.
Non-porous silica particles, as received, were heat treated (900° C.) in air for 10 h. The surface of the particles were rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the particles were then modified as described below.
Superficially porous silica layers are formed on nonporous silica core material, prepared by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols) {Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. The initial 2 layers were formed using 12 nm sols to create a bumpy surface.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte was removed by thermal treatment in air at 560° C. (10-20 hours). The bumpy particles were then exposed to elevated temperature (100° C.) and pH (8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177}. The layer-by-layer approach as described above was continued using different sized sols (6 nm) as compared to the initial layers, until a total of 8 layers were deposited on the surface of the core. The polyelectrolye was removed using the same thermal treatment as described above followed by a second thermal treatment at 900° C. for 10-20 hours. A rehydroxylation step was performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particle was then modified with a hybrid layer using the surface modification process employed in Examples CC-15, CC-16, or CC-17.
The process as described in Examples CC-19 or CC-20 is further expanded to include the same and/or varying sol sizes for different layers ranging from 1-100 nm to create initial sol layers ranging from 1-40 layers and total sol layers from 1-40 layers.
Following the reasoning from Example CC-19, an example in which superficially porous particles were made using a higher temperature thermal treatment is below:
Non-porous silica particles, as received, were heat treated (900° C.) in air for 10 h. The surface of the particles was rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the particles was then modified as described below.
Superficially porous silica layers can be formed on nonporous silica core material, by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf. Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols) {Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 8 layers of the same size nanoparticles were used.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte was removed by thermal treatment in air (540° C.) for 20 hours. To further strengthen these materials, a second thermal treatment (1000° C. vs. 900° C. in previous examples) was employed for 2.5 hours. A rehydroxylation step was then performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particles was then modified with hybrid using the process below:
The superficially porous particles were fully dispersed in toluene (13 mL/g). An azeotropic strip (111° C., 1 h) was then performed to remove residual water from the material. These initial anhydrous conditions are important as they ensure water content accuracy when water is added in the subsequent step. The reaction temperature was reduced to <40° C. while 100% BTEE PEOS (0.821 g PEOS/g particle) was added and allowed to stir for 10 minutes followed by 0.04 g water/g particle. The reaction was stirred for an additional 10 minutes at <40° C. before the temperature was increased to 80° C. for 1 h. The reaction was then heated to 111° C. and two additional azeotropic strips were performed at half hour intervals to remove excess water, and the volume of water removed was recorded. The reaction was held at 110° C. for 20 h. After a 20 h hold, the reaction was cooled to RT and the particles were isolated via filtration. The particles were subsequently washed twice with ethanol (10 ml/g) then redispersed in 70/30 (v/v) water/ethanol (10 mL/g). Ammonium Hydroxide (1 g NH4OH/g particle) was added and the mixture was stirred at 50° C. for 4 h. The reaction was then cooled<40° C. and the particles were isolated via filtration. The isolated particles were washed (10 ml/g) using the following sequence: 2× methanol/water (1:1 v/v), 2× methanol. Finally, the isolated, surface modified particles were dried for 16 h at 70° C. under 25 mm vacuum. The above process was repeated a second time.
To ensure uniformity of the hybrid layer produced above, the modified particles were exposed to elevated temperatures (115° C.) and pH (8) following the hydrothermal treatment process as noted by Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.
Example 22 is expanded to include thermal temperature treatments on the superficially porous particles in a range from 900-1300° C. these particles can then follow the general process as described in Examples CC-15, CC-16 or CC-17.
As is, or surface modified non-porous silica particles as those described in Examples CC-2-CC-9, are heat treated (750-1300° C.) in air for 10-24 h. The surface of the particles are rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum. The surface of the particles are then modified as described below.
Superficially porous silica layers are formed on nonporous silica core material, prepared by the general approach of Stuber {U.S. Pat. No. 3,634,558; J. Coll. Interf Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer is formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols) {Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 1-40 layers of the same size or different sized nanoparticles are used using the process as described in Examples CC-15, CC-19, CC-20, or CC-21.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte is removed by thermal treatment in air at temperatures greater than 500-600° C. (10-20 hours). To further strengthen these materials, a second thermal treatment at 825-1000° C. for 10-20 hours is employed. A rehydroxylation step is performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the superficially porous particles are then modified with a core-coating material using the surface modification process as described in Examples CC-15 or CC-16.
As is, or surface modified non-porous silica particles as those described in Examples CC-2-CC-9, are heat treated (750-1300° C.) in air for 10-24 h. The surface of the particles are rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried in at 80° C. under 25 mm vacuum.
In this process superficially porous silica layers are formed on non-porous core material using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. The porous layer is formed in a layer-by-layer approach using alternating additions of polyelectrolyte and the same size or different size silica nanoparticles (or silica sols) {Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396. In this example, the layering process is stopped a single or multiple times before the final superficially porous particle is created. During this hold, a core-coating material is attached, using a process similar to, but not limited by Example CC-2, to the surface of the intermediate particle to create an impervious layer core-coating the core and sol layer(s). Once the core-coating material is attached, the layering process is continued until the desired thickness of porous layer is achieved (1-40 layers) (
As detailed in Lawrence (US 20130112605, US 20130206665}, the polyelectrolyte is removed by thermal treatment in air at temperatures greater than 500-600° C. (10-20 hours). To further strengthen these materials, a second thermal treatment at 825-1000° C. for 10-20 hours is employed. A rehydroxylation step is performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The superficially porous particles can then be further modified using the surface modification process as described in Examples CC-15, CC-16 or CC-17.
As an alternative method to hydrothermal treatment for reducing microporosity post-surface modification and/or attaining a uniform coverage of pH stable core-coating material, one can use the following process at any point, in combination with or without the surface modification methods as detailed in Example CC-16 or CC-17:
Two grams of HPLC grade silica sorbent was dried at 160° C. for 2 hours in an air friction oven then cooled under dry nitrogen. Vacuum glassware components necessary for a simple bulb to bulb vapor transfer were dried in the same manner, assembled hot and cooled under dry nitrogen. The entire vacuum glassware assembly, with dried silica in bulb A and nothing in bulb B, was evacuated to 0.05 mm Hg. Bulb A was isolated and held under static 0.05 mm Hg vacuum. Bulb B was vented to dry nitrogen, infused with 4.2 grams of tetramethyldisilafuran, and re-evacuated to 0.1 mm Hg. Bulbs A and B were independently isolated from the vacuum pumping system. Tetramethyldisilafuran vapor was introduced into bulb A by allowing the bulbs A and B to equilibrate. After 2.5 hours of equilibration, the pressure in the bulbs was 8 mm Hg. Bulb A was isolated and held at reduced pressure and room temperature for 5 days. Bulb A was then vented to dry nitrogen and heated to 80° C. in an oil bath under dry nitrogen. The tetramethyldisilafuran vapor treated silica was transferred to a pressure filter, washed with twice with aliquots of toluene and aliquots of acetone, and vacuum dried overnight at 80° C. Portions of the untreated silica and the tetramethyldisilafuran vapor treated silica were analyzed by % C, nitrogen sorption and He pyncnometry. The tabulated analysis results (Table CC-3) are consistent with tetramethyldisilafuran vapor condensation and reaction in the micropores of the base silica.
The process as described in Example CC-25 can be followed in combination with or without the surface modification methods as detailed in Examples CC-16 or CC-17 using superficially porous particles as prepared in the process below. Here, the general process as described in Example CC-26 is expanded to include monomer and polymer inorganic and/or organic materials in place of or in addition to tetramethyldisilafuran, such as 1,1,3,3,5,5-hexaethoxy-1,3,5-trisilacyclohexane, and/or as noted in patents [US 2014031905, 20150133294, 20150136700, 20130319086, 20130273404, 20130112605, 20130206665, 2012055860, 20110049056, 20120141789, 20140194283, 20090209722, 20100076103 as well as U.S. Pat. Nos. 9,248,383, 9,145,481, 9,120,083, 8,778,453, 8,658,277, 7,919,177, 7,223,473, 6,686,035]. This process may be repeated 1-60 times.
Superficially porous silica layers can be formed on nonporous silica core material, by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf. Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using controlled cores from Example CC-1 and alternating additions of polyelectrolyte and silica nanoparticles (or silica sols){Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 8-12 layers of the same size nanoparticles are used.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte is removed by thermal treatment in air (540° C.) for 20 hours. To further strengthen these materials, a second thermal treatment (900° C.) is employed for 20 hours. A rehydroxylation step is then performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
The surface of the control core particles from Example CC-1 were modified as described below.
Superficially porous silica layers can be formed on nonporous silica core material, by the general approach of Stöber {U.S. Pat. No. 3,634,558; J. Coll. Interf Sci., 1968, 26, 62}, using a polyelectrolyte layering process described by Lawrence {US 20130112605, US 20130206665}, Kirkland {US 20070189944; 20080277346}, Blue {J. Chromatogr. A, 2011, 1218 (44), 7989}, and Brennan {J. Mater. Chem., 2012, 22, 13197}. In this process a porous layer was formed in a layer-by-layer approach using alternating additions of polyelectrolyte and silica nanoparticles (or silica sols){Muriithi, B. W. Ph.D. Thesis, University of Arizona, 2009, pp. 396}. In this process 12 layers of the same size nanoparticles were used.
As detailed in Lawrence {US 20130112605, US 20130206665}, the polyelectrolyte was removed by thermal treatment in air (540° C.) for 20 hours. To further strengthen these materials, a second thermal treatment (900° C.) was employed for 20 hours. A rehydroxylation step was then performed using the process described in Example 64 of Lawrence {US 20130112605, US 20130206665}.
For the same reasoning as described in Example CC-26, one can use the following process at any point, in combination with or without the surface modification methods as detailed in Examples CC-16 or CC-17:
Tetramethyldisilafuran was thoroughly mixed with superficially porous particles (7.7 g/g particles) in a round bottom flask. The slurry was evacuated (25 mm Hg) thrice while stirring. The flask was vented, slowly heated to 80° C. under a nitrogen atmosphere, then held at temperature for 2.7 h. Upon cooling<40° C., the material was washed twice with toluene and then twice with acetone (5 mL/g). The material was dried overnight 80° C. under 25 mm vacuum.
The process as described in Example CC-28, after the initial heat treatment and rehydroxylation, is further expanded to include monomer and polymer inorganic and/or organic materials in place of Tetramethyldisilafuran, such as 1,1,3,3,5,5-hexaethoxy-1,3,5-trisilacyclohexane, and/or as noted in patents [US 2014031905, 20150133294, 20150136700, 20130319086, 20130273404, 20130112605, 20130206665, 2012055860, 20110049056, 20120141789, 20140194283, 20090209722, 20100076103, as well as U.S. Pat. Nos. 9,248,383, 9,145,481, 9,120,083, 8,778,453, 8,658,277, 7,919,177, 7,223,473, 6,686,035]. This process may be repeated 1-60 times.
Non-porous silica particles, as received, were heat treated (900° C.) in air for 10 h. The surface of the particles were rehydroxylated using 10% v/v nitric acid at 100° C. for 16 h, then dried at 80° C. under 25 mm vacuum.
Zirconium butoxide (80 wt % in 1-butanol) solution was added (1 g/g particle) to a premixed solution of 1:0.012 wt/wt butanol:stearic acid (6.5 g/g particle). The solution was then stirred at 200 rpm for 1 h. To a separate beaker, water (1.8 g) and butanol (70.4 g) was added to 13 g of the above NPS silica particles. The particles were thoroughly dispersed via sonication. The slurry was then added to the butanol/stearic acid/zirconium mixture and agitated for 21 min at 150 rpm. The mixture was then quenched with acetone (350 g) and allowed to settle. The supernatant was decanted and the quenching process was repeated. After the second decanting, the material was air dried (16 h) then thermally treated in air at 120° C. for 3 h, 450° C. for 3 h, and then 750° C. for 5 h. The particles were then sized to isolate singlet particles from agglomerates. The resulting core-coating material averaged in a thickness of 45 nm by FE-SEM, indicating thick coverage of core-coating material.
The process from Example CC-30 is further expanded to include alumina, titanium oxide, cerium oxide or mixtures thereof.
The following non-limiting examples describe superficially porous chromatographic materials. The materials in these Examples may or may not have a core-coating composition applied. One of ordinary skill in the art would be able to use the techniques described herein and in the coating material examples above to prepare the materials of the invention.
All reagents were used as received unless otherwise noted. Those skilled in the art will recognize that equivalents of the following supplies and suppliers exist and, as such, the suppliers listed below are not to be construed as limiting.
Those skilled in the art will recognize that equivalents of the following instruments and suppliers exist and, as such, the instruments listed below are not to be construed as limiting.
The % C, % H, % N values were measured by combustion analysis (CE-440 Elemental Analyzer; Exeter Analytical Inc., North Chelmsford, MA) or % C by Coulometric Carbon Analyzer (modules CM5300, CM5014, UIC Inc., Joliet, IL). The specific surface areas (SSA), specific pore volumes (SPV) and the average pore diameters (APD) of these materials were measured using the multi-point N2 sorption method (Micromeritics ASAP 2400; Micromeritics Instruments Inc., Norcross, GA). The SSA was calculated using the BET method, the SPV was the single point value determined for P/P0>0.98 and the APD was calculated from the desorption leg of the isotherm using the BJH method. Scanning electron microscopic (SEM) image analyses were performed (JEOL JSM-5600 instrument, Tokyo, Japan or Hitachi SU8030 instrument, Dallas, TX) at 1-7 kV. Focused ion beam scanning electron microscopic (FEB/SEM) image analyses were performed by Analytical Answers Inc. (Woburn, MA) on an FEI Model 200 Focused Ion Beam instrument, and a Hitachi S4800 Ultra-Field emission SEM. Particle sizes were measured using a Beckman Coulter Multisizer 3 analyzer (30 μm aperture, 70,000 counts; Miami, FL) or manually using SEM. Particles were prepared for cross-sectional imaging using a broad ion beam milling system (Hitachi IM 4000 plus). The particle diameter (dp) was measured as the 50% cumulative diameter of the volume based particle size distribution or mode of the number based particle size distribution. The width of the distribution was measured as the 90% cumulative volume diameter divided by the 10% cumulative volume diameter (denoted 90/10 ratio). Metals content was measured by ICP-AE (Thermo Fisher Scientific iCAP 6500 Duo). Light scattering particle size measurements were measured using a Malvern Mastersizer 2000 in water. Particle size measurements of nanoparticles and Zeta-potential measurements were made using a Malvern ZetaSizer NanoSeries (model ZEN3600). Multinuclear (13C, 29Si) CP-MAS NMR spectra were obtained using a Bruker Instruments Avance-300 spectrometer (7 mm double broadband probe). The spinning speed was typically 5.0-6.5 kHz, recycle delay was 5 sec. and the cross-polarization contact time was 6 msec. Reported 13C and 29Si CP-MAS NMR spectral shifts were recorded relative to tetramethylsilane using the external standards adamantane (13C CP-MAS NMR, δ 38.55) and hexamethylcyclotrisiloxane (29Si CP-MAS NMR, δ −9.62). Populations of different silicon environments were evaluated by spectral deconvolution using DMFit software. [Massiot, D.; Fayon, F.; Capron, M.; King, I.; Le Calvé, S.; Alonso, B.; Durand, J.-O.; Bujoli, B.; Gan, Z.; Hoatson, G. Magn. Reson. Chem. 2002, 40, 70-76]. Classification techniques are described, for example, in W. Gerhartz, et al. (editors) Ullmann's Encyclopedia of Industrial Chemistry, 5th edition, Volume B2: Unit Operations I, VCH Verlagsgesellschaft mbH, (Weinheim, Fed. Rep. Germ. 1988). Magnetic measurements were made using a vibrating sample magnetometer (ADE/DMS Model 880) by ArKival Technology Corporation (Nashua, NH). Phase characterization were made by Wide Angle X-Ray Powder Diffraction (XRPD) analysis (H&M Analytical Services, Inc. Allentown, N.J.), using a Bruker D4 diffractometer (Cu radiation at 40 KV/30 mA). Scans were run over the angular range of 10° to 90° 2-Theta with a step size of 0.02° and a counting time of 715 seconds per step.
Nonporous hybrid particles were formed following a modification of a reported process {Choi, J. Y.; Kim, C. H.; Kim, D. K. J. Am. Ceram. Soc., 1998, 81, 1184-1188. Seog, I. S; Kim, C. H. J. Mat. Sci., 1993, 28, 3277-3282}. To a clean 40 mL vial was added a stir bar, water (26 mL) and 14.8 M NH4OH (4.3 mL). This solution was then heated to 60° C. with stirring (600 rpm) in a water bath before one or more alkoxysilanes, including phenyltriethoxysilane (PTES, Gelest, Morrisville, PA), 1,8-bis(triethoxysilyl)octane (BTEO, Gelest, Morrisville, PA), 1,2-bis(triethoxysilyl)ethane (BTEE, Gelest, Morrisville, PA), 1,2-bis(methyldiethoxysilyl)ethane (BMDEE, Gelest, Morrisville, PA), vinyltriethoxysilane (VTES, Gelest, Morrisville, PA), or mercaptopropyltrimethoxysilane (MPTMS, Lancaster Chemical, Lancaster UK) were added (3 mL total). The reaction was sealed, and returned to the 60° C. water bath for 2 h. The reaction was further continued for 24 h at 25° C. The particles were isolated by repeated centrifugation from water (3×40 mL) and then ethanol (3×40 mL). The particles were then air dried for 12 h and vacuum dried (70° C., 30 mm Hg) for 24 h. Carbon content was determined by combustion analysis. Average particle size was determined by SEM. These experiments differ from the prior reports in the use of bridging hybrid silanes (BTEO, BTEE, and BMDEE) which are known to have increased high pH stability, as well as the use of synthetically relevant groups. For example, particles containing surface vinyl groups can be further reacted by the following transformation (not limited to); oxidation, polymerization, radical addition or metathesis. Particles containing surface thiol groups can be further reacted by the following transfonnation (not limited to); oxidation, radical addition, or disulfide bond formation. Particles containing surface phenyl groups can be further reacted by the following transformation (not limited to); protodesilylation or aromatic substitution. As shown in
Nonporous hybrid particles were formed following a modification of a reported process {U.S. Pat. Nos. 4,983,369 and 4,911,903}. To a clean Nalgene bottle (125 mL) was added a stir bar, water (14 mL), ethanol (80 mL), and NH4OH (7 mL, 14.8 M). One or more alkoxysilanes, including tetraethoxysilane (TEOS, Gelest, Morrisville, PA), phenyltriethoxysilane (PTES, Gelest, Morrisville, PA), or mercaptopropyltrimethoxysilane (MPTMS, Lancaster Chemical, Lancaster UK) were added with stirring (600 rpm, 4 mL, 25° C.). The reaction was sealed and the onset of turbidity was monitored. The formation of spherical particles was further monitored over 24 h by light microscopy. The particles were purified and isolated by repeated centrifugation from ethanol (3×100 mL) and water (3×100 mL). The particles were air dried for 12 h and then vacuum dried (70° C., 30 mm Hg) for 12 h. Carbon content was determined by combustion analysis. Average particle size was determined by SEM.
Product 2c was thermally treated in an air muffled oven at 700° C. for 3 h. The resulting nonporous silica product (3a) had no organic content.
One or more organoalkoxysilanes (all from Gelest Inc., Morrisville, PA or United Chemical Technologies, INC., Bristol, PA) were mixed with ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ) and 0.1 N hydrochloric acid (Aldrich, Milwaukee, WI) in a flask. The resulting solution was agitated and refluxed for 16 hours in an atmosphere of argon or nitrogen. Alcohol was removed from the flask by distillation at atmospheric pressure. Residual alcohol and volatile species were removed by heating at 95-120° C. for 1-2 hours in a sweeping stream of argon or nitrogen. The resulting polyorganoalkoxy siloxanes (POS) were clear viscous liquids. The chemical formulas are listed in Table 3 for the organoalkoxysilanes used to make the product POS. Specific amounts are listed in Table 4 for the starting materials used to prepare these products.
Following a modified process of WO2008103423, An aqueous mixture of Triton® X-100 (5.6 g, X100, Dow Chemical, Midland, MI), deionized water and ethanol (52 g, EtOH; anhydrous, J. T. Baker, Phillipsburg, NJ) was heated at 55° C. for 0.5 h. In a separate flask, an oil phase solution was prepared by mixing a POS (58 g) from Example 4 for 0.5 hours with toluene (Tol; HPLC grade, J. T. Baker, Phillipsburg, NJ). Under rapid agitation, the oil phase solution was added into the EtOH/water/X100 mixture and was emulsified in the aqueous phase using a rotor/stator mixer (Model 100L, Charles Ross & Son Co., Hauppauge, NY). Thereafter, 30% ammonium hydroxide (44 mL, NH4OH; J. T. Baker, Phillipsburg, NJ) was added into the emulsion. Suspended in the solution, the gelled product was transferred to a flask and stirred at 55° C. for 16 h. Formed particles were isolated on 0.5 μm filtration paper and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburgh, NJ). The particles were then dried at 80° C. under vacuum for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 5. The % C values, specific surface areas (SSA), specific pore volumes (SPV) and average pore diameters (APD) of these materials are listed in Table 5. Materials prepared by this approach are highly spherical by SEM (
Non-porous particles are prepared by thermal treatment of porous silica and hybrid inorganic/organic particles in an air muffled oven at 1,000-1,200° C. for 20-40 hours. Example of porous hybrid particles included (but are not limited to) examples in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. The resulting nonporous silica products have no organic content. These materials maintain the general morphology and particle size distribution of the feed material. Average particle size decreases in this process. The degree of particle size decrease depends on the composition, density and porosity of the feed material. Any agglomerated materials are removed through grinding or classification. This approach is suitable to prepare products with 90/10 ratios<1.20 and 90/10 ratios between 1.20-1.55. Differences in particle size distributions impacts packed bed structure and pressure of packed beds of chromatographic materials.
Following the reports of Kievsky {IEEE Transactions on Nanotechnology, 2005, 4, 5, 490}, rod shaped materials were prepared through the hydrochloric acid catalyzed hydrolysis of tetraethoxysilane (TEOS, Gelest, Morrisville, PA) in water in the presence of cetyltrimethyl ammonium chloride (CTAC, Aldrich, Milwaukee, WI). Products were collected on a filter and were washed with water and methanol. The products were dried under vacuum (80° C., 12 h) and were submitted for SEM characterization. Depending on concentration of water (336 mL), hydrochloric acid (0.8-1.7 mol), CTAC (0.02-0.04 mol) and TEOS (0.02 mol), initial agitation, reaction time and temperature (4-25° C.) a variety of different material morphologies were generated, including straight rods, bent rods, spirals, and spherical particles. This approach is suitable to prepare products with distributions of lengths and thicknesses. Isolation of sized samples and removal of any agglomerated materials is achieved through classification. Differences rod lengths and thickness are an important variable that impacts packed bed structure and pressure of packed beds, alone or in a mixture with spherical particle packings.
Modification of experiment detailed in Example 7 to replace tetraethoxysilane with the use one or more of the following (but not limited to): phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(triethoxysilyl)ethane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane; hexyltrimethoxysilane; chloropropyltriethoxysilane; chloropropyltrimethoxysilane; octadecyltrimethoxysilane; octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane; 3,3.3-trifluoropropyltrimethoxysilane; 3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; 3-cyanobutyltrimethoxysilane; methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane; acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane; chloroethyltriethoxysilane; chloroethyltrimethoxysilane; fluorotriethoxysilane; or fluorotrimethoxysilane alone or in a mixture with tetraethoxysilane or tetramethoxysilane. Products were collected on a filter and were washed with water and methanol. The products are dried under vacuum (80° C., 12 h) and are submitted for SEM characterization. Through optimization of reagents and temperature conditions a variety of different material morphologies are generated, including straight rods, bent rods, spirals, and spherical particles. Removal of excess surfactant is achieved through extraction. Isolation of sized samples and removal of any agglomerated materials is achieved through classification. This approach is suitable to prepare products with distributions of lengths and thicknesses. Isolation of sized samples and removal of any agglomerated materials is achieved through classification. Differences rod lengths and thickness are an important variable that impacts packed bed structure and pressure of packed beds, alone or in a mixture with spherical particle packings.
Modification of experiment detailed in Example 7 to replace tetraethoxysilane with the use one or more of the following (but not limited to): phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(triethoxysilyl)ethane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane; hexyltrimethoxysilane; chloropropyltriethoxysilane; chloropropyltrimethoxysilane; octadecyltrimethoxysilane; octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane; 3,3.3-trifluoropropyltrimethoxysilane; 3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; 3-cyanobutyltrimethoxysilane; methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane; acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane; chloroethyltriethoxysilane; chloroethyltrimethoxysilane; fluorotriethoxysilane; or fluorotrimethoxysilane alone or in a mixture with tetraethoxysilane or tetramethoxysilane. Products were collected on a filter and were washed with water and methanol. The products are dried under vacuum (80° C., 12 h) and are submitted for SEM characterization. Through optimization of reagents and temperature conditions a variety of different material morphologies are generated, including straight rods, bent rods, spirals, and spherical particles. Removal of excess surfactant is achieved through extraction. Isolation of sized samples and removal of any agglomerated materials is achieved through classification. This approach is suitable to prepare products with distributions of lengths and thicknesses. Isolation of sized samples and removal of any agglomerated materials is achieved through classification. Differences rod lengths and thickness are an important variable that impacts packed bed structure and pressure of packed beds, alone or in a mixture with spherical particle packings.
The porosity of products obtained in Example 7 and 8 are reduced by thermal treatment in an air muffled furnace at 700-1,200° C. for 10-72 hours. Isolation of sized samples and removal of any agglomerated materials is achieved through classification.
Selected products from Examples 8 and 9, or porous silica (SSA between 5-1,000 m2/g; SPV between 0.1-1.6 cm3/g; and APD between 10-1000 Å) and hybrid inorganic/organic particles (SSA between 5-1,000 m2/g; SPV between 0.1-1.6 cm3/g; and APD between 10-1000 Å) are partially or completely pore filled with a mixture of one or more of the following; polymer, polymerizable monomer, silane, polyorganosiloxanes, or nanoparticles (5-200 nm) of diamonds, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, silicon, silica carbide, cerium or any oxides thereof. The use of nanoparticles of diamonds allows for improved thermal conductivity of these materials. The use of ferromagnetic and ferrimagnetic nanoparticles, includes (but is not limited to): magnetite (ferrous ferric oxide); maghemite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co). These magnetic materials allow for magnetic capture and processing of these materials. Examples of silanes and polyorganosilanes include (but are not limited to) those included in Example 4 and Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. Examples of polymers include latexes, epoxides, methacrylates, styrene, divinyl benzene, polysaccharides, dendrigrafts, hyperbranched polymers, and others included in Polymer Handbook {4th edition, J. Brandrup; E. H. Immergut; E. A. Gnulke; editors: Wiley: Hoboken, N J, 1999}. The filling of these porous particles can be performed by creating a mixture of additives in a solvent including (but not limited to) methylene chloride, water, acetone or ethanol followed by slow evaporation using an efficient rotary evaporator (0-78° C., 1-24 h), to yield a free flowing powder. Alternatively, dry powder can be tumbled with additives in a polyethylene bottle at 0-100° C. for 1-24 h), to yield a free flowing power. The powder produced can be washed with a suitable solvent including (but not limited to) ethanol or methanol.
When silanes or polyorganosiloxanes are employed as additives, hydrolytic condensation can be performed using an aqueous solution of ammonium hydroxide and an alcohol, including (but not limited to) ethanol, isopropanol, or methanol. After stirring for 2-20 hours the product is collected on a filter and is washed with water and methanol or acetone. The product is dried under vacuum (80° C., 12 h) and is submitted for SEM characterization.
When polymerizable monomers are employed as additives, polymerization is performed using an appropriate initiator including (but not limited to) free radical initiators, ring opening polymerization catalysts, metathesis catalysts, and living polymerization catalysts. After stirring for 2-20 hours the product is collected on a filter and is washed with water and toluene or acetone. The product is dried under vacuum (80° C., 12 h) and is submitted for SEM characterization.
This process is repeated as needed to further reduce porosity and increase amounts of additives in the pore structure. Interval approaches of silanes or polyorganosiloxanes additives with polymer additives are performed as needed to further reduce porosity and increase amounts and types of additives in the pore structure. Layered or repeating structures of additives can be prepared by this approach. For example, a composite material containing both diamonds and magnetite would be beneficial for thermal conductivity improvements and magnetic capture processing. A material that contains alumina or titania is suitable for glycopeptides, phosphopeptide and phospholipids separations. A material that contains ceria may be suitable for phospholipid and phosphatidylcholines separations.
Materials prepared by this approach are free flowing and maintain the general morphology and particle size distribution of the porous feed material. This approach is suitable to prepare products with 90/10 ratios<1.20 and 90/10 ratios between 1.20-1.55. SPV decreases in this process. Exemplary products of this process are nonporous. The degree of porosity reduction depends on the amount of additives incorporated in the pore structure. Any agglomerated materials can be removed through grinding or classification.
Composite materials of Example 10 are thermally treated at 700-1,200° C. for 10-40 hours to further reduce SPV. This thermal treatment is performed in air, under an inert atmosphere, or in a reducing atmosphere depending on compatibility of the additives employed Materials containing diamond or magnetite employ an inert or reducing atmosphere is used to prevent oxidation.
Materials prepared by this approach are free flowing and maintain the general morphology and particle size distribution of the porous feed material. SPV decreases in this process. Exemplary products of this process are nonporous. The degree of porosity reduction depends on the composition, density and porosity of the feed material. Any agglomerated materials can be removed through grinding or classification.
Following the report of Zhang {Functional Materials Letters, 2010, 3, 2, 125.1 spheroidal magnetite particles were prepared through the solvothermal reaction of iron trichloride. In a 600 mL stainless steel autoclave equipped with a removable glass liner and an overhead mixer a mixture of anhydrous iron (III) chloride (Fisher Scientific), deionized water, ethylene glycol (Sigma-Aldrich, St. Louis, MO), polyethylene glycol (PEG 3400, Sigma-Aldrich, St. Louis, MO) and urea (Sigma-Aldrich, St. Louis, MO) were stirred at 50° C. until completely dissolved. The headspace was evacuated under vacuum and the pressure reactor was sealed before being heated (with or without stirring) to 220° C. and was held at this temperature overnight. The reactor was cooled to ambient temperature. Products were isolated in a magnetic separator, and were washed by repeated resuspension in deionized water. Specific reaction data is provided on Table 6. Percent conversion of iron trichloride to magnetite was determined by iron concentrations analysis by digestion in hydrochloric acid and complexation with potassium thiocyanate. Magnetic properties were determined by VSM. Phase confirmation was determined by XRD. Particle size and standard deviation were determined by measuring individual particles by SEM (minimum particles counted≥60). The effects of temperature, solvent, cosolvent, reagent concentrations, and stirring speed were investigated as part of the process optimization. Specific product data are listed in Table 6. As shown in
Magnetite core particles (0.1-0.5 μm) from Example 12 are reacted with tetraethoxysilane in an aqueous ammonical ethanol solution following a general process described by Example 2, U.S. Pat. Nos. 4,983,369, 4,911,903, Giesche {J. Eur. Ceram. Soc., 1994, 14, 189; J. Eur. Ceram. Soc., 1994, 14, 205} or Nozawa {Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2005, 72 (1), 011404}. The product of this is a free flowing powder with a thick silica shell material. The final particle sizes for these materials are controlled between 0.8-1.7 μm through changes in reaction conditions. Products are isolated by centrifugation, magnetic capture or filtration, and are washed with copious amounts of water and methanol. The product is air dried before drying under vacuum (80° C., 12 h) and is submitted for SEM characterization. Any agglomerated materials can be removed through grinding or classification. Products prepared by this approach have little to no porosity. This silica layer on magnetite is advantageous because it reduces iron dissolution and reduces undesired secondary interactions between analytes and the magnetite surface during a chromatographic separation.
The process described in Example 13 is applied to other materials, including ones prepared in Examples 1-3, 5-11 as well as diamond, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, silicon, silica carbide, cerium or any oxides thereof. The size of these materials is between 0.01-2.0 μm. These materials can exist as dispersed particles or aggregates of nanoparticles. The silica layer thickness is controlled in this process through changes in reaction conditions and can produce final product sizes between 0.8-5 μm. Any agglomerated materials can be removed through grinding or classification. Products prepared by this approach are free flowing and have little to no porosity. While this approach is applicable to a variety of different feed morphologies, a significant degree of rounding occurs during this process. This rounding increases with silica layer thickness, and can decrease the observation of flat surfaces or sharp edges on these materials. This is advantageous for use as liquid chromatographic packing since sharp edges can lead to increase material fracturing and fines generation during packing of the chromatographic device.
The process described in Example 13 is applied to other materials having non-spherical morphologies, including (but not limited to) spirals, capsules rings, discoidal, concave disks, spools, rings, helix, saddles, cross, cube, derby, helix, cylinders, and tubes. Examples of dumbbell, doughnut, rod, spiral, and gyroid shaped materials have been reported {Doshi, N. PNAS, 2009, 106, 51, 21495; Alexander, L. Chem. Commun., 2008, 3507; Naik, S. J. Phys. Chem. C 2007, 111, 11168; Pang, X. Microporous and Mesoporous Materials 2005, 85, 1; Kievsky, Y. IEEE Transactions on Nanotechnology, 2005, 4, 5, 490; Sugimoto, T. in Monodispersed Particles, (Elsevier Science BV, Amsterdam) 2001; Ozin, G. Adv. Mater., 1997, 9, 662}. Examples of ferrimagnetic and ferromagnetic iron oxide rings and capsules have been reported {Wu, W. J. Phys. Chem. C 2010, 114, 16092; Jia, C.-J. J. Am. Chem. Soc. 2008, 130, 16968}. The external diameter of these feed materials is between 0.2-5 μm. The silica layer thickness is controlled in this process through changes in reaction conditions and produces final external sizes between 0.3-5.5 μm. Any agglomerated materials can be removed through grinding or classification.
The process described in Example 13-15 is modified to replace tetraethoxysilane with one or more of the following (but not limited to): phenyltriethoxysilane; phenyltrimethoxysilane; phenylethyltriethoxysilane; phenylethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4 bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane; hexyltrimethoxysilane; chloropropyltriethoxysilane; chloropropyltrimethoxysilane; octadecyltrimethoxysilane; octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane; 3,3.3-trifluoropropyltrimethoxysilane; 3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and 3-cyanobutyltrimethoxysilane alone or in a mixture with tetraethoxysilane or tetramethoxysilane.
The silica shell thickness is controlled in this process through changes in reaction conditions and can produce final product sizes between 0.8-1.7 μm. Any agglomerated materials can be removed through grinding or classification. Products prepared by this approach are free flowing and have little to no porosity.
Selected products in Example 13-16 are thermally treated at 700-1,200° C. for 10-72 hours to further reduce SPV. This thermal treatment is performed in air, under an inert atmosphere, or in a reducing atmosphere depending on the additives employed. When additives of diamond or magnetite are used, an inert or reducing atmosphere is used to prevent oxidation.
Materials prepared by this approach are free flowing and maintain the general morphology and size distribution of the porous feed material. SPV decreases in this process. Exemplary products of this process are nonporous. The degree of porosity reduction depends on the composition, density and porosity of the feed material. Any agglomerated materials can be removed through grinding or classification.
Product 12j (0.2 g, 496 nm) from Examples 11 was twice washed with deionized water (500 mL) followed by twice washing with an aqueous solution of 0.7% poly(vinylpyrrolidone) (PVP, MW=360,000, 400 mL, Aldrich). Materials were isolated in a magnetic separator. The material was then dispersed in an aqueous solution of 0.7% PVP (400 mL) using sonication (10 minutes), followed by gentile agitation for 16 hours. The material was then allowed to completely settle and the volume was reduced by 28 mL. The mixture was then transferred to a round bottom flask equipped with overhead stirring and a condenser. To this mixture was added anhydrous ethanol (200 mL, JT Baker) and 28% (w/v) ammonium hydroxide (28 mL, Fisher Scientific). This mixture was stirred at ambient temperature for 20 minutes.
In a separate flask a solution of distilled tetraethoxysilane (0.388 mL, TEOS, Gelest) was diluted in anhydrous ethanol (4.00 mL). This solution was then added to the particle mixture in four equal aliquots spaced 20 minutes apart, with continued stirring. The reaction was then allowed to continue for an additional 60 minutes. Materials were isolated in a magnetic separator and were washed twice with anhydrous ethanol and twice with deionized water.
This material was resuspended in 0.7% PVP (400 mL) and the growth process described above was repeated until the final particle size was achieved. The product (18a) was isolated in a magnetic separator and was washed twice with anhydrous ethanol and five times in deionized water. A sample of this product was submitted for SEM analysis. Particle size and standard deviation was determined by measuring individual particles by SEM (minimum particles counted≥60). The final product indicated a final particle size of 1.198±0.119 μm.
The alkoxysilanes used in Example 1 are modified to include substituted benzenes, including (but not limited to) 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane. Bridging arylene materials have been shown to have improved thermal stability over traditional hybrid inorganic/organic materials{Shea, K. J. Non-Cryst. Solids, 1993, 160, 234}. Particles prepared by this approach are spherical and free flowing.
The alkoxysilanes used in Example 2 are modified to include substituted benzenes, including (but not limited to) 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane. Materials prepared by this approach are free flowing and have improved thermal stability over traditional hybrid inorganic/organic materials.
Superficially porous silica layers are formed on selected hybrid core materials from Example 1, 2, 19 and 20 using a modified process described by Kirkland {US 20070189944; 20080277346}. In this approach 0.8-1.7 μm hybrid core materials are treated with a 0.1-0.5 wt % solution of one or more polyelectrolytes including (but not limited to): poly(diallydimethylammonium chloride, polyethylenimine and poly(allylamine hydrochloride) in water. The molecular weight of these polyelectrolytes can vary between 2,000 and 500,000. These materials are washed with water using repeated centrifugation, before redispersing in water. A 2-10 wt % solution of silica sols (8-85 nm) is then added with mixing. These materials are washed with water using repeated centrifugation. This process of polyelectrolyte treatment followed by washing, silica sol treatment, and washing can be repeated until a final particle size is achieved. Final drying of product is performed in a vacuum oven or lyophilizer at ambient to elevated temperatures.
Products prepared in this manner have both silica sols and polyelectrolyte on the core material. In order to remove the polyelectrolyte thermal treatment at temperatures greater than 500° C. (10-20 hours) is employed. To further strengthen these materials, a second thermal treatment at 825-1300° C. for 10-20 hours is employed. These thermal treatments are performed in air, under an inert atmosphere, or in a reducing atmosphere depending on the additives employed. When additives of diamond or magnetite are used, an inert or reducing atmosphere is used to prevent oxidation.
While materials prepared by this process are free flowing spherical superficially porous materials with rough surface features, the thermal treatments steps remove all carbon content from these materials. Expected improvement in chemical stability of a hybrid core in chromatographic applications is not realized by this approach. Similar performance with commercially available silica superficially porous materials is achieved by this approach.
The polyelectrolyte of Example 21 is modified to include the use of chemically degradable polymers, including (but not limited to) polyethylene glycol, polypropylene glycol, polymethacrylate, polymethylmethacrylate, poly(acrylic acid), and polylactic acid based polymers containing pendant primary, secondary, or tertiary amino groups. For example, polyethylene glycol (PEG) based polyether amines are described in U.S. Pat. No. 7,101,52, and others are commercially available as Jeffamine polyetheramines (Huntsman Corporation).
Products prepared in this manner have both silica sols and polymer on the core material. In order to remove the polymer, different approaches are employed that do not require thermal treatment at or above 500° C. Polymethylmethacrylate networks can be decomposed using β-ray irradiation. Acrylate and methacrylate polymer backbones having thermally cleavable tertiary ester linkages can decompose between 180-200° C. {Ogino, K. Chem. Mater, 1998, 10, 3833}. Polyethylene glycol groups can be removed by oxidative degradation {Andreozzi, R. Water Research, 1996, 30, 12, 2955; Suzuki, J. J. Applied Polymer Science, 1976, 20, 1, 93} and microwave assisted template removal using nitric acid and hydrogen peroxide {Tian, B. Chem. Commun., 2002, 1186}. A listing of other degradable polymer backbones and degradation mechanism is reported in Degradable Polymers: Principles and Applications {Editors G. Scott and D. Gilead, D., Chapman & Hall (Kluwer) 1995}.
Materials prepared by this process are free flowing spherical superficially porous particles with rough surface features, Expected improvements in chemical stability of a hybrid core in chromatographic applications are realized by this approach. Improvements in chemical stability of these superficially porous particles over commercially available silica superficially porous particles are achieved by this approach.
After polymer degradation, there is a substantial reduction of polymer containing primary, secondary or tertiary amino groups remain within these superficially porous materials. Further processing steps can be performed to further reduce and remove this polymer content. Any agglomerated materials or fine materials can be removed through classification.
These particles still contain carbon content of the core hybrid particles. To improve pore diameter and further strengthen these superficially porous materials, hydrothermal treatment method of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423} are employed. Alternatively a surrounding material method described by Wyndham {WO 2010/141426} can be used to strengthen these superficially porous materials. The addition of a surrounding material decreases the porosity of these materials. The surrounding material method is of particular importance when a hybrid inorganic/organic surrounding material is used on the silica-sol superficially porous layer. Such materials have improved chemical stability over commercially available silica superficially porous particles. When the surrounding material contains nanoparticles, including (but not limited to) nanodiamonds—as noted in Examples 12 and 13 of Wyndham {WO 2010/141426}—improvements in thermal conductivity can be achieved.
The core material of Example 21 is modified to include the precursor or product materials from Examples 5-18. Included in this are spherical, irregular, rod-shaped and toroid-shaped materials. Included in this are 0.5-1.5 μm cores that are diamond, magnetite, coated diamond, or coated magnetite.
The core material of Example 22 is modified to include the precursor or product materials from Examples 5-18. Included in this are spherical, irregular, rod-shaped and toroid-shaped materials. Included in this are 0.5-1.9 μm cores that are diamond, magnetite, coated diamond, or coated magnetite.
The silica sol used in Examples 21-24 is modified to include the use of hybrid sols. Hybrid sols are prepared by the condensation of hybrid inorganic/organic alkoxysilanes in the presence or absence of a tetraethoxysilane or tetramethoxysilane. Similar sol sizes can be achieved in this approach (8-85 nm) by this approach. Alternatively a hybrid layer can be formed by surface modifying preformed silica sols (8-85 nm). The use of a hybrid core material and chemically degradable polymers containing pendant primary, secondary, or tertiary amino groups described in Example 22, allows for the formation of hybrid superficially porous materials. Alternatively 0.8-1.9 μm nonporous silica cores are used. These materials contain carbon content of the core and porous layers. To improve pore diameter and further strengthen these superficially porous materials, hydrothermal treatment method of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 20081103423} are employed. Alternatively a surrounding material method described by Wyndham {WO 2010/141426} can be used to strengthen these superficially porous materials. No high temperature thermal treatment (>600° C.) is used in this approach.
The process of Examples 21-25 is modified to replace a part of all of sols used with similar size sols, including (but not limited to) diamonds, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, silicon, silica carbide, cerium or any oxides thereof.
The process of Examples 21-26 is modified to include incorporation of one or more nanoparticles within the superficially porous layer, including (but not limited to) nanoparticles listed in Example 10.
Nonporous silica particles (1.26 μm, 10.4 g), that were previously thermally treated at 600° C. (10 h) and rehydroxylated using 10% nitric acid (Fisher scientific) were dispersed in 80 mL of solvent (water:anhydrous ethanol 2:1 v/v) by sonication for 10 minutes. Separately, octadecyltrimethylammonium bromide (0.43 g, C18TAB, Sigma-Aldrich) was dissolved in 80 mL of solvent (water:anhydrous ethanol 2:1 v/v). The C18TAB solution was then added into the particle solution and was sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of pluronic P123 (8.44 g, Sigma-Aldrich) was dissolved in 240 mL of solvent (water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B (240 mL) was added into solution A (160 mL) and was sonicated for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and stirred at 600 rpm. Ammonium hydroxide solution (30%, 12 mL, J. T. Baker) was added into the flask and allowed to continue stirring for 5 minutes. 1,2-bis(triethoxysilyl)ethane (2.3 mL, BTEE, Gelest) was then added over a minute. The reaction was allowed to continue with stirring for an hour. The final concentrations reagents used were C18TAB (2.6-10.5 mM), Pluronic P123 (3.5-13.8 mM), and BTEE (0.015-0.030 M).
During the washing step, the sample was diluted four times the sample volume with deionized water followed by centrifugation (Forma Scientific Model 5681, 2,500 rpm, 6 min). The wash sequence was repeated two times using sonication to redisperse particles.
The growth process was repeated three times to yield four hybrid layers on the nonporous silica core. With each layer the volume of solution A (5-7 vol %), solution B (6 vol %) and ammonium hydroxide (3-10 vol %) were increased to compensate for the increase in solids volume after each growth layer while maintaining the concentration of the reagents constant Amounts of C18TAB, BTEE and ethanol/water used are shown on Table 7. Products were isolated by centrifugation and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). The particles were then air dried and vacuum dried at 80° C. under vacuum for 16 hours. Products were submitted for SEM analysis.
Reactions in this process used <3 mM C18TAB. Very little hybrid layer growth was observed in this approach. In contrast increased aggregation and elevated amount fine particle (<1 μm) were observed.
Nonporous silica particles (10.4 g, 1.26 μm), that were previously thermally treated at 600° C. (10 h) and rehydroxylated using 10% nitric acid (Fisher scientific), were dispersed in 100 mL of solvent (water anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes. Separately, octadecyltrimethylammonium bromide (2.46 g, C18TAB, Sigma-Aldrich) was dissolved in 100 mL of solvent (water anhydrous ethanol 2:1 v/v). The C18TAB solution was then added into the particle solution and was sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of Pluronic P123 (39.0 g, Sigma-Aldrich) was dissolved in 400 mL of solvent (water anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B (400 mL) was added into solution A (200 mL) and allowed to continue sonicate for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and stirred at 750 rpm. Ammonium hydroxide solution (30%, 24 mL, J. T. Baker) was added into the flask and allowed to continue stirring for 5 minutes. 1,2-bis(triethoxysilyl)ethane (6 mL, BTEE, Gelest) was first diluted with anhydrous ethanol (dilution factor=3) and then added to the flask with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at a constant flow rate (50 μL/min). The reaction was allowed to continue stirring until all BTEE was added, allowed to stir for an extra hour before washing. The final concentrations reagents used were C18TAB (2.6-17.27 mM), Pluronic P123 (3.5-22.16 mM), and BTEE (0.020-0.030 M).
The wash steps were performed as detailed in Example 28. The growth process was done once to grow a hybrid layer on the nonporous silica core. Reaction details are included on Table 8. Products were isolated by centrifugation and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). The particles were then air dried and at 80° C. under vacuum for 16 hours. Products were submitted for SEM analysis. Particle size was determined by measuring individual particles by SEM. As shown in Table 8, and increase in C18TAB concentration (2.6-13.6 mM) results in an increase in shell thickness (0.04-0.16 μm) by this approach. Similar to Example 28, reactions using less than 3 mM C18TAB had increased aggregation and elevated amount fine particle (<1 μm) were observed Concentrations of C18TAB between 8-17 mM were advantageously used to result in well formed products.
An initial hybrid growth layer is formed on rehydroxylated nonporous silica particles (0.8-1.7 μm, 10.4 g) using a modified process for Product 29b. These core particles can have 90/10 ratios<1.20 or 90/10 ratios between 1.2-1.55. In this reaction 1,2-bis(triethoxysilyl)ethane (6 mL, BTEE, Gelest) is first diluted with anhydrous ethanol (dilution factor=3) and is added to the flask with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at 5-100 μL/min. The particle size is monitored during this growth process. The reaction is allowed to continue stirring until the target particle size is reached or all BTEE is added. The mixture is allowed to stir for an extra hour before the wash steps, which are performed as detailed in Example 28.
This process is repeated for products requiring one or more additional hybrid growth layers. Increases in C18TAB, Pluronic P123, ethanol, and ammonium hydroxide are made to maintain a low concentration of solids. C18-TAB concentration is maintained between 8-11 mM, and the mol ratio of C18-TAB/Pluronic P123 was maintained at 1.3:1. Optimization experiments showed that lower ratios of these two surfactants leads to increased aggregation. BTEE is diluted with anhydrous ethanol (dilution factor≥3) and is added to the reaction at a flow rate of 5-100 μL/min. The particle size of these materials is monitored during this growth process. The reaction is allowed to continue stirring until the target particle size is reached or all BTEE is added. The mixture is allowed to stir for an extra hour before the wash steps, which are performed as detailed in Example 28.
Products are isolated by centrifugation and are washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). The products are then air dried and at 80° C. under vacuum for 16 hours. Products are submitted for SEM, and FIB/SEM analysis. Particle size is determined by measuring individual particles by SEM. As listed in Table 9, final products have an average particle size of 1.2-2.7 μm, with shell thickness varying from 0.03-0.60 μm. Products prepared by this approach are free flowing, spherical and have a smooth surface. Products 30a, 30b, and 30g are prepared in one layer. Products 30c-f, 30-h-l are prepared in two to four growth layers. Products 30m-p are prepared in 5-15 layers. This approach allows for superficially porous materials with different physical properties to be prepared. For example Products 30d and 30g (1.30 μm); Products 30e and 30 h (1.50 μm); Products 30f, 30i and 30 k (1.70 μm); and Products 30m and 30n (2.30 μm) have similar final particle size, but vary in shell thickness and the ratio of shell thickness to radius of the core. The ratio of shell thickness to core radius can be modified over a large range by this approach (0.04-0.71).
The process of Examples 30 is modified to have a superficially porous layer formed in a single continued growth layer using rehydroxylated nonporous silica particles (0.8-2.5 μm). These core particles can have 90/10 ratios<1.20 or 90/10 ratios between 1.2-1.55. In this reaction 1,2-bis(triethoxysilyl)ethane (BTEE, Gelest), diluted with anhydrous ethanol (dilution factor=3), is added with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at 5-100 μL/min. A second solution containing octadecyltrimethylammonium bromide (C18TAB, Sigma-Aldrich), water, ethanol, Pluronic P123 (Sigma-Aldrich) and ammonium hydroxide solution (30%, 24 mL, J. T. Baker) is added using a separate peristaltic pump at a constant rate in order to maintain concentrations of C18TAB, water, ethanol, Pluronic P123, ammonium hydroxide within a range between the rate required to maintain a uniform ratio of particle surface area (m2) to reaction volume, to the rate required to maintain a uniform ratio of particle volume (m3) to reaction volume. The particle size of these materials is monitored during this growth process. The reaction is allowed to continue stirring until the target particle size is reached or all BTEE is added. The mixture is allowed to stir for an extra hour before the wash steps, which are performed as detailed in Example 28.
Final products have an average particle size of 1.0-2.9 μm, with shell thickness varying from 0.03-0.60 μm. Products are submitted for SEM, and FIB/SEM analysis. Particle size is determined by measuring individual particles by SEM. Products prepared by this approach are free flowing, spherical and have a smooth surface. Analysis of particle by FIB/SEM shows evidence of a single step process, having no observable interlayer contrast.
1.26 μm nonporous silica particles (10.4 g) that were previously thermally treated at 600° C. (10 h) and rehydroxylated using 10% nitric acid (Fisher scientific) were used in this process.
A silica layer was formed by the following process. Particles were dispersed in 80 mL of solvent (water:anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes. Separately, octadecyltrimethylammonium bromide (0.46 g, C18TAB, Sigma-Aldrich) was dissolved in 80 mL of solvent (water:anhydrous ethanol 2:1 v/v). The C18TAB solution was added into the particle solution and the mixture was sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of Pluronic P123 (8.44 g, Sigma-Aldrich) was dissolved in 240 mL of solvent (water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B (240 mL) was added into solution A (160 mL) and was sonicated for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and stirred at 750 rpm. Ammonium hydroxide solution (30%, 12 mL, J. T. Baker) was added into the flask and allowed to continue stirring for 5 minutes. Tetraethoxysilane (4.6 mL, TEOS, Sigma-Aldrich) was added in two steps. First 2.3 mL of TEOS was added and the reaction was continued for 30 minutes before an additional 2.3 mL of TEOS was added and the reaction allowed continuing for an hour. The wash steps were performed as detailed in Example 28.
A hybrid layer was formed on these particles using the following process. Particles were redispersed in 100 mL solvent (water:anhydrous ethanol 2:1 v/v) by sonication. Separately, octadecyltrimethylammonium bromide (3.0 g, C18TAB, Sigma-Aldrich) w as dissolved in 100 mL of solvent (water:anhydrous ethanol 2:1 v/v). The C18TAB solution was then added into the particle solution and was sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of Pluronic P123 (58 g, Sigma-Aldrich) was dissolved in 400 mL of solvent (water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B (400 mL) was added into solution A (200 mL) and allowed to continue to sonicate for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and was stirred at 750 rpm. Ammonium hydroxide solution (30%, 24 mL, J. T. Baker) was added into the flask and was stirred for 5 minutes. In this growth step 1,2-bis(triethoxysilyl)ethane (6 mL, BTEE, Gelest) was first diluted with anhydrous ethanol (dilution factor=3) and was added to the flask with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at 50 μL/min. Once all the BTEE was added the reaction was allowed to continue for an hour. The product was isolated and was washed as detailed in Example 28.
A silica layer was then grown on the hybrid layer using the silica layer process described above, but the volume of the solution was increased to compensate for the increase in solids volume while maintaining a constant concentration of the reagents. A hybrid layer was formed on this silica layer using the hybrid layer process described above, but the volume of the solution was increased to compensate for the increase in solids volume while maintaining a constant concentration of the reagents.
Reaction details are included on Table 10. Products were isolated by centrifugation and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). The particles were then air dried and at 80° C. under vacuum for 16 hours. Products were submitted for SEM analysis. Particle size was determined by measuring individual particles by SEM. The requirement of increased amounts of C18TAB and Pluronic P123 for acceptable hybrid layer growth (32L2 and 32L4) is evident in this data. When C18TAB concentrations were <5 mM, little to no hybrid layer growth is observed.
This process was repeated separately to prepare two additional products. The first (product 32a) had a silica followed by hybrid layer. The second (product 32b) had a silica followed by two consecutive hybrid layers, resulting in an increased hybrid content near the exterior surface.
The process of Example 28-32 is modified to use tetraethoxysilane in the first layer followed by 1,2-bis(triethoxysilyl)ethane or a mixture of tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane in the following layer. This solution varies from 0-99 vol % tetraethoxysilane. This sequence is repeated (2-15 times) to create a distinct silica and hybrid layers. By changing reaction conditions the thickness of the silica porous layer and the hybrid porous layers can be modified between 10-1000 nm. The composition of this 1,2-bis(triethoxysilyl)ethane and tetraethoxysilane mixture can vary for each layer, creating an enriched hybrid content at the external porous surface. Alternatively the composition of this 1,2-bis(triethoxysilyl)ethane and tetraethoxysilane mixture can vary for each layer, creating enriched silica content at the external porous surface. For the general process of Examples 29-31, the composition of a mixed tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane solution can be modified by changing the feed alkoxysilane solution over the course of these reactions.
The process of Example 28-32 is modified to use 1,2-bis(triethoxysilyl)ethane in the first layer followed by 1,2-bis(triethoxysilyl)ethane or a mixture of tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane in the following layer. This solution varies from 1-100 vol % tetraethoxysilane. This sequence is repeated (2-15 times) to create a distinct hybrid and silica layers. By changing reaction conditions the thickness of the hybrid porous layers can be modified between 10-1000 nm. The composition of this 1,2-bis(triethoxysilyl)ethane and tetraethoxysilane mixture can vary for each layer, creating an enriched hybrid content at the external porous surface. Alternatively the composition of this 1,2-bis(triethoxysilyl)ethane and tetraethoxysilane mixture can vary for each layer, creating enriched silica content at the external porous surface. For the general process of Examples 29-31, the composition of a mixed tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane solution can be modified by changing the feed alkoxysilane solution over the course of these reactions.
The core material of Example 28-34 is modified to include the precursor or product materials from Examples 1-3, or 5-20. Included in this are spherical, irregular, rod-shaped and toroid-shaped materials. Included in this are 0.5-1.9 μm cores that are hybrid, diamond, magnetite, coated diamond, or coated magnetite.
The process of Examples 28-35 is modified to replace a part of all of the alkoxysilane used with one or more of the following silanes (but not limited to) listed in Example 16 and 19, Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177}, Wyndham {WO 2008/103423}, or a POS used in Example 4.
The process of Examples 28-36 is modified to replace a part of all of the alkoxysilane used with one or more of the following metal oxide precursors (but not limited to): the oxide, hydroxide, ethoxide, methoxide, propoxide, isopropoxide, butoxide, sec-butoxide, tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide, 2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate, nitrate, chlorides, and mixtures thereof of titanium, zirconium, iron, copper, niobium, cobalt, cerium or aluminum. Advantageously, the metal oxide precursors are methyl titanium triisopropoxide, methyl titanium triphenoxide, titanium allylacetoacetatetriisopropoxide, titanium methacrylate triisopropoxide, titanium methacryloxyethylacetoacetate triisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide, pentamethylcyclopentadienyl titanium trichloride, and zirconium methacryloxyethylacetoacetate tri-n-propoxide.
The process of Examples 28-37 is modified to include incorporation of one or more nanoparticles within the superficially porous layer, including (but not limited to) nanoparticles listed in Example 10.
The process of Examples 28-38 is modified to add or replace part or all of the ionic and or non-ionic surfactants with one or more polyectrolyte or polymers detailed in Examples 21 or 22.
The surfactants and or polymers used in select products from Examples 28-39 are removed by extraction in a 1-2 M solution of hydrochloric acid in methanol, ethanol or acetone, at elevated temperatures (30-90° C.) for 1-20 hours. Products are isolated on isolated on 0.5 μm filtration paper and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). This process can be repeated 1-3 times to further remove surfactants and or polymers from these particles. Products are dried at 80° C. under vacuum for 16 hours and are submitted for carbon, CP-MAS NMR, SEM, and nitrogen sorption analysis. For products that contain hybrid content in the shell or porous layer, carbon content is present in the product. Identification of the hybrid product species is made using 13C and 2Si CP-MAS NMR spectroscopy. The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials used in these reactions. Products prepared by this approach are free flowing. Any agglomerated materials can be removed through grinding or classification.
The surfactants and or polymers used in select products from Examples 28-40 are removed by ozonolysis in water at low to moderate temperatures (0-30° C.) for 1-20 hours. Products are isolated on isolated on 0.5 μm filtration paper and washed consecutively with copious amounts of water and methanol (HPLC grade, J. T. Baker, Phillipsburg, NJ). This process can be repeated 1-3 times to further remove surfactants and or polymers from these particles. This process can be combined with an acid extraction approach detailed in Example 40. Products are dried at 80° C. under vacuum for 16 hours and are submitted for carbon, CP-MAS NMR, SEM, and nitrogen sorption analysis. For products that contain hybrid content in the shell or porous layer, carbon content is present in the product. Identification of the hybrid product species is made using 13C and 29Si CP-MAS NMR spectroscopy. The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials used in these reactions. Products prepared by this approach are free flowing. Any agglomerated materials can be removed through grinding or classification.
The surfactants and or polymers used in select products from Examples 28-41 are removed by 500° C. (10-20 hours) is employed. To further strengthen these superficially porous materials, increased thermal treatment at 825-1,000° C. in air for 10-20 hours is employed. Products prepared by this approach are free flowing. Any agglomerated materials can be removed through grinding or classification.
The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials used in these reactions. While materials prepared by this process are free flowing superficially porous particles, the thermal treatments steps remove all carbon content from these materials. Expected improvement in chemical stability of a hybrid superficially porous material in chromatographic applications is not realized by this approach.
When the superficially porous materials of Examples 28-41 contain arylene-bridged hybrids, the surfactants and or polymers used in select products from Examples 28-41 are removed by 390-490° C. (10-20 hours) in air or under a nitrogen atmosphere. Products are submitted for carbon, CP-MAS NMR, SEM, and nitrogen sorption analysis. For products that contain hybrid content in the shell or porous layer, carbon content is present in the product. Identification of the hybrid product species is made using 13C and 29Si CP-MAS NMR spectroscopy. The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials used in these reactions. Products prepared by this approach are free flowing. Any agglomerated materials can be removed through grinding or classification.
To improve pore diameter and further strengthen select materials from Examples 28-43, hydrothermal treatment methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} or Wyndham {WO 2008/103423} are employed. Alternatively, when a material from Examples 28-39 are used that have a surfactant or polymer additive, hydrothermal treatments are used to improve pare diameter. Alternatively a surrounding material method described by Wyndham {WO 2010/141426} can be used to strengthen these superficially porous materials. The surrounding material method is of particular importance when a hybrid inorganic/organic surrounding material is used on the silica superficially porous layer. In this instance, the hybrid inorganic/organic surrounding material reduces the porosity. Such materials have improved chemical stability over commercially available silica superficially porous particles. When the surrounding material contains nanoparticles, including (but not limited to) nanodiamonds—as noted in Examples 12 and 13 of Wyndham {WO 2010/141426}-improvements in thermal conductivity can be achieved. Products, after surfactant or polymer removal, have pore diameters between 60 Å and 350 Å.
A series of superficially porous materials were prepared following a multi-step process: (1) Stuber seeds preparation using tetraethoxysilane (TEOS); (2) core growth using TEOS; (3) hybrid layer growth using a mixture of TEOS and octadecyltrimethoxysilane (C18TMOS); (4) classification to remove fines; (5) calcination to introduce porosity; (6) pore processing steps; (7) re-calcination to improve mechanical strength; (8) rehydroxylation; and (9) surface bonding.
The seeds were prepared by a modified Stuber process. Uniform sized silica can be prepared (0.1-2.0 μm) depending on the concentration of TEOS, composition of the hydrolysis solution, temperatures, and mixing. In current studies, TEOS addition rate was fixed at 0.044 g/mL and hydrolysis solution consisted of ethanol, water and 30% ammonium hydroxide solution at volume ratio of 80/14/7, respectively. Increased mixing levels during seed formation resulted in higher content of aggregates. Optimal mixing conditions were determined to be initial vigorous shaking for 15 seconds before maintaining the reaction unstirred. This approach resulted in less than 5 wt % aggregates.
The cores were further grown with concurrent additions of TEOS and hydrolysis solution (ethanol, waters, and ammonium hydroxide). Additional hydrolysis solution was added to prevent reseeding and aggregation/agglomeration events. Solvent conditions were optimized by exploring ternary phase diagrams to ensure the TEOS was miscible in the aqueous ethanol mixture. Typical addition rates of TEOS and the hydrolysis solution were set at 0.125 mL/min and 1 mL/min, respectively, and the reaction temperature was 50° C. Core size was verified using light scattering, Coulter Counter, or SEM.
Upon achieving the desired core size, the TEOS reservoir was switched to a mixture of C18TMOS and TEOS to grow a hybrid layer on the core particles. Molar ratios of C19TMOS/TEOS varied from ¼ to 1/9. Advantageous molar ratios are from ¼ to ⅙. Due to differing solubility of C18TMOS and TEOS the relative addition rates of silanes and hydrolysis solution were adjusted to ensure miscibility. Conditions were based on the ternary phase diagrams of C18TMOS/TEOS mixtures, water and ethanol. The process was monitored by light scattering, Coulter Counter, and SEM. Table 11 details experiments performed in ethanol/water/30% ammonium hydroxide (80/14/7 v/v/v). Table 12 details experiments with varied hydrolysis solutions.
Classification was performed, if needed, to remove fines, aggregates and/or agglomerates. A variety of classification techniques (e.g., sedimentation, elutriation, and centrifugation) can be used to for this separation.
Materials were calcined at 500° C. (1° C./min and held at temperature for 12 hours) in air to remove the organic groups and introduce porosity. Products prepared using a 1/9 molar ratio of C18TMOS/TEOS had a SSA between 298-337 m2/g; SPV between 0.20-0.23 cm3/g; and an APD between 25-27 Å. Products prepared using a ¼ molar ratio of C18TMOS/TEOS had a SSA between 505-508 m2/g; SPV between 0.38-0.41 cm3/g; and an APD between 27-28 Å. These APD are too small to be useful in most HPLC and UPLC applications.
In order to enlarge the pore diameter, a variety of pore processing steps were explored, detailed in Table 13. Process B allowed for the largest increase in pore diameter (APD=126-272 Å) when the temperature was between 150-200° C. At temperatures between 60-100° C. smaller changes pore diameters were achieved (APD=27-47 Å). Process A allowed for a noticeably lower increases in pore diameter (APD=37-94 Å at 100-150° C.). Process C allowed for increases in pore volume (SPV) to be achieved (˜0.1 cm3/g) along with small increases in APD (<50 Å). Process A or B was also used after Process C to further increase pore diameter. Results for process C were very dependent on the lot, purity, and concentration of the ammonium bifluoride as well as reaction time. It also appears this increase in porosity came at the expense of mechanical strength. Alternatively, increased porosity was achieved through modification of the molar ratio in step 3. An advantageous molar ratio of C18TMOS/TEOS is ¼. Optimal pore processing was achieved using alkaline hydrothermal treatments at pH 8 (e.g., Process B). Table 14 provides details on selected prototypes. Alternative modifications using other pore modification processes can be performed [U.S. Pat. No. 7,223,473; EP2181069; WO2006106493; US publication 20080269368; Chem. Commun., 2007, 1172; Chem Commun, 2007, 111 (3), 1093; Solid State Science, 2003, 5, 1303; Coll. Surf. A, 2003, 229, 1].
In order to increase the mechanical strength of these materials for use in HPLC and UPLC, a second calcination step was performed at 800° C. (1° C./min then held at temperature for 12 hours). In order to prepare these materials for surface modification a rehydroxylation reaction was performed in dilute hydrofluoric acid. Particle size and polydispersity were measured using Coulter Counter or light scattering. As shown in
Surface bondings were performed on these materials using standard procedures using octadecyltrichlorosilane (ODTCS) or octadecyldimethylchlorosilane (ODDMCS). Materials were further endcapped using monofunctional chlorosilanes using standard protocols. Prototypes data is provided in Table 15. Surface coverage was determined by difference in % C data before and after surface modification. Products were further packed into chromatographic columns and evaluated for performance (e.g., van Deemter analysis).
Example 45 (steps 1-4) is modified to include the precursor or product materials from Examples 1-3, or 5-20. Included in this are spherical, irregular, rod-shaped and toroid-shaped materials. Included in this are 0.5-1.9 μm cores that are hybrid, diamond, magnetite, coated diamond, or coated magnetite. A further modification is not to include steps 5-9.
The process of Examples 45-46 is modified to replace a part of all of the alkoxysilane used with one or more of the following silanes (but not limited to) listed in Example 16 and 19, Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177}, Wyndham {WO 20081103423}, or a POS used in Example 4. A further modification is not to include steps 5-9 of Example 45.
The process of Examples 45-47 is modified to replace a part of all of the alkoxysilane used with one or more of the following metal oxide precursors (but not limited to) listed in Example 37. A further modification is not to include steps 5-9 of Example 45.
The process of Examples 45-48 is modified to include incorporation of one or more nanoparticles within the superficially porous layer, including (but not limited to) nanoparticles listed in Example 10. A further modification is not to include steps 5-9 of Example 45.
To a clean round bottom flask, equipped with a stir bar, thermometer and condenser was added tetraethoxysilane (Gelest, Morrisville, PA) and one equivalent of octadecanol, dodecanol, octanol, 2-ethoxyethanol, or 3-ethyl-3-pentanol (all alcohols were from Aldrich, Milwaukee, WI). A catalytic amount of p-toluene sulfonic acid was added, and the solution was stirred and heated overnight at 90° C. under nitrogen. Ethanol generated in this process was removed using a rotovap with regular vacuum. The product alkoxysilane was separated by vacuum distillation (2 mm Hg) to yield separate products having the following formula;
(CH3CH2O)4-vSi(OR*)v (Formula XXb)
wherein
The monoderivatized product (v=1, R*=octadecyl, dodecyl, octyl, 2-ethoxyethyl) were isolated in ≥90% purity by gas chromatography.
The process of Examples 28-39, 45-49 is modified to employ a three component alkoxysilane mixture to form a superficially porous layer of formula XX
(D)d(E)e(F)f (Formula XX)
Example 51 is modified to have a two component initially condensed formula (d=0). When F includes a silane from Example 50 the produce is reacted by repeated acid extraction (as detailed in Example 40) to create a superficially porous layer.
Selected materials from Examples 45-49 and 51-52 are further processed following the processes described in Examples 40-44. Classification is performed if needed to improve the particle size distribution, removing any fines or agglomerated materials.
Selected precursor and product core materials from Examples 1-3, or 5-20 are surface modified with an alkoxysilane that contains a basic group of equation 1, using the surface modification methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}
R(CH2)nSi(Y)3-x(R′)x (equation 1)
R′ independently represents an alkyl, branched alkyl, aryl, or cycloalkyl group;
Selected precursor and product core materials from Examples 1-3, or 5-20 are surface modified with an alkoxysilane that contains a basic group of equation 2, using the surface modification methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}
A(CH2)nSi(Y)3-x(R′)x (equation 2)
R′ independently represents an alkyl, branched alkyl, aryl, or cycloalkyl group.
Selected nanoparticulate materials detailed in Examples 10, 12, 14, 21, 22, 25, 26, 27, 37, and 38 are surface modified with an alkoxysilane that contains a basic group of equation 1 or 2, using the surface modification methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.
Selected surface modified core materials in Example 54 and 55 are reacted with surface modified nanoparticulate materials in Example 56 using a modified process detailed in Example 21. In this approach no polyelectrolyte is used. Solution pH adjusted for optimal porous layer formation. In certain aspects, the solution pH varies between pH 2-7. In certain aspects, the optimal pH can vary between pH 4.0-6.5. When a positively charged surface modified core material from Example 54 is used, a negatively charged nanoparticulate material from Example 56 is used. When a negatively charged surface modified core material from Example 55 is used, a positively charged nanoparticulate material from Example 56 is used.
After workup and isolation this single layered material can be used as is. Alternatively, additional layers can be added. These can be achieved by repeating this layering process using a nanoparticulate material from Example 56 of opposite charge from the last surface layer. When the last surface layer used positively charged nanoparticulate material from Example 56, the following layer uses a negatively charged nanoparticulate material from Example 56. When the last surface layer uses a negatively charged nanoparticulate material from Example 56, the following layer uses a positively charged nanoparticulate material from Example 56. This sequence of alternating charge nanoparticulate material can be used to form 2-15 layers on the core material. In this approach no polyelectrolyte material used. The type of nanoparticulate material used can vary between layers or remain the same. For example, a silica layer can be layered between diamond or magnetite layers by this approach.
The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials used in these reactions. Products prepared by this approach are free flowing. Any agglomerated materials can be removed through grinding or classification.
To improve pore diameter and further strengthen these superficially porous materials of select materials from Examples 40-43, hydrothermal treatment methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} or Wyndham {WO 2008/103423} are employed. Alternatively a surrounding material method described by Wyndham {WO 2010/141426} can be used to strengthen these superficially porous materials. The surrounding material method is of particular importance when a hybrid inorganic/organic surrounding material is used on the silica superficially porous layer. Such materials have improved chemical stability over commercially available silica superficially porous particles. When the surrounding material contains nanoparticles, including (but not limited to) nanodiamonds—as noted in Examples 12 and 13 of Wyndham {WO 2010/141426}-improvements in thermal conductivity can be achieved.
Alternatively, products are thermally treated at 700-1,000° C. for 10-40 hours to further strengthen these superficially porous materials. This thermal treatment is performed in air, under an inert atmosphere, or in a reducing atmosphere depending on compatibility of the additives employed. Materials containing diamond or magnetite employ an inert or reducing atmosphere is used to prevent oxidation.
The process of 57 is modified to introduce a polyelectrolyte or polymer material from Example 21-27. When the last layer used a positively charged nanoparticulate material, the following polyelectrolyte or polymer used is negatively charged. When the last layer used a negatively charged nanoparticulate material, the following polyelectrolyte or polymer used is positively charged.
The process of 57-58 is modified to introduce layers formed with polyelectrolyte and layers formed without polyelectrolyte.
The process of 57-59 is modified to use charged nanoparticulate materials that have been charged modified through acid or base washing, or electrostatically. The charge of these nanoparticulate materials can be monitored through zeta-potential measurements.
The process of 57-60 is modified to hybrid core materials that have surface acid or base groups. Surface acidic groups can be prepare using hybrid core materials of the type described in Example 1-3 and 5 using phenyltriethoxysilane, or mercaptopropyltrimethoxysilane. The phenyl groups can be sulfonated by heating in sulfuric acid. The mercaptopropyl group can be oxidized to sulfopropyl groups using hydrogen peroxide or nitric acid. The use of a protected aminopropyl group in a hybrid core material of the type described in Example 1-3 and 5 can be used to create surface basic groups. Methyl iodide treatment of these amino groups can be used to prepare dimethyl and trimethyl aminopropyl groups.
The process of 57-61 is modified to use hybrid nanoparticulate materials that have surface acid or base groups of the type detailed in Example 61.
Select materials from Examples 21-43, 45-49, 51-52, and 57-61 are further processed following the processes described in Examples 40-44. Classification is performed if needed to improve the particle size distribution, removing any fines or agglomerated materials.
Select superficially porous materials prepared according to Examples 21-43, 45-49, 51-52, and 57-63 are dispersed in a 1 molar hydrochloric acid solution (Aldrich, Milwaukee, WI) for 20 h at 90-98° C. Alternatively materials are rehydroxylated in a 10% nitric acid solution, or dilute hydrofluoric acid (aqueous). Products are isolated on filter paper (or a magnetic separator) and are washed repeatedly with deionized water until a neutral pH is achieved, followed by acetone (HPLC grade, J. T. Baker, Phillipsburg, N.J.).
Materials can be further treated by sedimentation in acetone to remove fines material. The products are dried at 80° C. under vacuum for 16 h. Superficially porous materials, prepared by this approach are submitted for analysis. The specific surface areas (SSA) and specific pore volumes (SPV) of these materials are increased with respect to the core materials. SPV vary between 0.08-0.45 cm3/g and average pore diameter varies between 60-300 Å. Particle size measurements and SEM analysis indicate the formation of thick superficially porous layer. This porous layer thickness varies between 0.07-0.53 μm, material average size varies between 1.2-15.0 μm, and the product size distribution (90/10 ratio) are similar to the size distribution of the core materials. The surface roughness of these materials varies from rough to smooth. Rough surfaces generally formed from sol-based approaches. Smooth surfaces from high purity alkoxysilane-based approaches. The product shape generally resembles the core materials. For example, when the cores are spherical, products are spherical. When cores are rod-shaped, products are rod-shaped. The noticeable difference is these products is a rounding of rough edges for jagged or flat faced core materials after the porous layer is formed.
Select spherical superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane following the general process described in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} or Wyndham {WO 2008/103423}. These materials are further reacted with trimethylchlorosilane following the general process described in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} or Wyndham {WO 20081103423}. Table 16 contains a description of these C18-bonded materials. Material compositions used the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y
In this table the following abbreviations are used: SM=Smooth Surface and RS=Rough Surface.
Products of this process are spherical having differences in particle size, distribution, surface morphology, shell thickness and composition. Products 65a-65h detail the different final particle size, 90/10 ratio, and surface roughness that can be achieved in this process while maintain a comparable ratio of shell thickness to radius of the core material (0.53). Products 65i-651 have different ratios of shell thickness to radius of the core material (0.29-0.64), while maintaining a comparable final product particle size. These materials can be compared further with Products 65a and 65b. Products 65m-65s have comparable particle size, distribution, morphology, shell thickness and ratio of shell thickness to radius core as Product 65a, but vary in composition (0-100% hybrid) in both the core and porous layer.
Select superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane following the process described in Example 65. Table 17 contains a description of these C18-bonded materials. These products contain irregular shaped diamond cores that can be coated with silica. The core material before formation of the superficially porous layer has an average particle size of 1.18 μm and a 90/10 ratio of 1.4. The products have an average particle size of 1.80 μm, which have a 0.31 um porous layer thickness and a ratio of porous layer thickness to core radius of 0.53. Porous layers composition uses the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y(nanodiamond)z
In this table the following abbreviations are used: SM=Smooth Surface; and RS=Rough Surface.
Products 66a-66h have differences in coating of the diamond cores, composition of the porous layer and surface roughness. Products 66i-66s have different composition of the porous layer to included nanodiamonds. In this approach nanodiamonds are incorporated within the porous layer in 0.1-16 wt %.
Select superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane following the process described in Example 65. Table 18 contains a description of these Cis-bonded materials. These products contain a magnetite core that has been coated with silica. The silica coated magnetite core material has an average particle size of 1.18 μm and a 90/10 ratio of 1.1-1.5. The products have an average particle size of 1.80 μm, which have a 0.31 um porous layer thickness and a ratio of porous layer thickness to core radius of 0.53. Porous layers composition uses the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y(nanodiamond)z
In this table the following abbreviations are used: SM=Smooth Surface; and RS=Rough Surface.
Products 67a-67l have different magnetite core size, coated core 90/10 ratio, and surface roughness, while having a comparable porous layer composition. Products 67m-67t have differences in the hybrid and nanodiamond content of the porous layer.
Select superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane following the process described in Example 65. Table 19 contains a description of these C18-bonded materials. These products contain rod shaped core materials. Rod shaped cores are described with a length to width notation. Material composition uses the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y(nanodiamond)z
In this table the following abbreviations are used: SM=Smooth Surface; and RS=Rough Surface; CSD=Cross Sectional Diameter; and CCSR=Core Cross Sectional Radius.
Product 68a-1 have changes in average core rod length (1-3 μm) and average core rod cross sectional diameter (CSD, 1-2 μm) and surface roughness, while having a comparable ratio of shell thickness to core rod cross sectional radius (CCSR). Products 68m-68p have changes in shell thickness to cross sectional radius and surface roughness, while having comparable core rod length and corm rod CSD. These products can be compared with 68a-b. Products 68q-ac have changes in composition of the core rod and porous layer, while other parameters are comparable to Product 68b.
Select superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane following the process described in Example 65. Table 20 contains data for of these Cis-bonded materials. These cores have toroid shaped iron oxide, silica, hybrid, or polymeric core materials. Alternatively these cores are coated with silica. Toroid shaped core materials are described as an outer diameter (OD), and inner diameter (ID) of open volume, and cross sectional diameter (CSD=0.5(OD-ID)) of material. Material composition uses the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y(nanodiamond)z
In this table the following abbreviations are used: SM=Smooth Surface; and RS=Rough Surface; OD=outer diameter; ID=Inner Diameter; CSD=Cross Sectional Diameter; and CCSR=Core Cross Sectional Radius.
Product 69a-g have changes in average product OD (1.63-8.06 μm), average core OD (1.5-7 μm) and core CSD (0.5-2 μm), while having a comparable ratio of shell thickness to core cross sectional radius (CCSR, 0.53). Products 69h-k have changes in ratio of average shell thickness to CCSR (0.3-0.6) and surface roughness, while having comparable average core OD and average core CSD. These products can be compared with 69d. Products 69l-p have changes in composition of the porous layer, while other parameters are comparable to Product 69d.
Select superficially porous materials prepared according to Example 64 are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane following the process described in Example 65. Table 22 contains data of these C18-bonded materials. These products contain composite spherical core particles that have an average particle size of 1.18 μm and a 90/10 ratio of 1.4. Porous layers composition uses the following notation:
(O1.5SiCH2CH2SiO1.5)x(SiO2)y(nanodiamond)z(nanotitania)1-(x+y+z)
These products have an average particle size of 1.80 μm, which have a 0.31 μm porous layer thickness and a ratio of porous layer thickness to core radius of 0.53.
Select materials prepared according to Example 64 and Cis-bonded materials prepared according to Example 65-70 are packed into 2.1×100 mm chromatographic columns using a slurry packing technique. The performance of these materials is evaluated using an ACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2 Chromatography Data Software is used for data collection and analysis. Columns are evaluated under a series of different tests described in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423; WO 2011/017418}, including isocratic reversed-phase (pH 3 and pH 7), gradient separations, and accelerated stability tests with high pH mobile phases.
Mixtures of spherical and rod shaped C18-bonded materials prepared according to Examples 65 and 68 are packed into 2.1×100 mm chromatographic columns using a slurry packing technique. The weight percent of rod-shaped materials varies from 1-95 wt %. The performance of these materials is evaluated using an ACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2 Chromatography Data Software is used for data collection and analysis. Reductions and column pressure and an increase in interstitial porosity and interstitial fraction is determined for columns containing increased content of rod-shaped materials. Interstitial fraction is well known in the art and can be determined by a number of known methods including (but not limited to) inverse size exclusion chromatography.
Following a modified process of Example 21, to a mixture of 0.5-1.0 μm diamond particles (5 g, Mypodiamond, Smithfield, PA) dispersed in deionized water (45 g) was added a 0.5 wt % aqueous solution of poly(diallydimethylammonium chloride) (225 g, MW=100,000-200,000, Aldrich, Milwaukee, WI). The mixture was stirred for 10 minutes and the treated particles were collected by centrifugation. The particles were washed by four-fold repeated dispersion in deionized water (250 mL), followed by centrifugation. The particles were redispersed in deionized water (150 mL) before addition of a 10 wt % aqueous solution of 59 nm silica sols (50 g, Nexsil 85NH4, Nyacol Nano Technologies, Ashland, MA, pH was adjusted to 2.98 using dilute nitric acid). The mixture was stirred for 15 minutes before collecting the particles by centrifugation. The particles were washed by five-fold repeated dispersion in deionized water (250 mL), followed by centrifugation (Product 73L1).
The particles were dispersed in deionized water (100 g) before addition of a 0.5 wt % aqueous solution of poly(diallydimethylammonium chloride) (225 g, MW=100,000-200,000, Aldrich, Milwaukee, WI). The mixture was stirred for 10 minutes and the treated particles were collected by centrifugation. The particles were washed by four-fold repeated dispersion in deionized water (250 mL), followed by centrifugation. The particles were redispersed in deionized water (150 mL) before addition of a 10 wt % aqueous solution of 59 nm silica sols (50 g, Nexsil 85NH4, Nyacol Nano Technologies, Ashland, MA, pH was adjusted to 2.98 using dilute nitric acid). The mixture was stirred for 15 minutes before collecting the particles by centrifugation. The particles were washed by five-fold repeated dispersion in deionized water (250 mL), followed by centrifugation (Product 73L2).
Aqueous samples were taken and air dried for SEM analysis (
A superficially porous silica layer was formed on the product 18a from Example 18 using a modified process of Example 21. Silica coated magnetic cores (18a, 1.2 μm, 20 mg) were resuspended in a 0.5 wt % aqueous solution of polyethylenimine (1.0 mL, PEI, MW=2,000, Aldrich). This mixture was then mixed on a rotator for 10 minutes. Materials were isolated using a magnetic separator and were washed four times with deionized water (3.0 mL, MilliQ) before being resuspended in deionized water (0.6 mL). A 10 wt % aqueous solution of 59 nm silica sols (200 μl, Nexsil 85NH4, Nyacol Nano Technologies, Ashland, MA, pH adjusted to 3.48) was then added. The mixture was rotated for 15 minutes, before isolating the product using a magnetic separator. The product was washed five times with deionized water (3.0 mL). The product (74L1) was isolated using a magnetic separator.
This process was repeated twice more to produce products a second (product 74L2) and third layer (product 7413). The final product was air dried on a Nucleopore filter (0.2 μm, Whatman). SEM analysis (
Products 73L2 and 74L3 are thermally treated under a nitrogen atmosphere at 500° C. and 800-900° C. following the process of Example 21. An inert atmosphere is used to prevent oxidation of the diamond or magnetite cores. Classification is performed to improve the particle size distribution and remove any fines or agglomerated materials. These materials are rehydroxylated using the process of Example 64 and are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane using the process of Example 65. C18-bonded diamond core superficially porous particles (product 75a) and C18-bonded magnetic core superficially porous particles (product 75b) are packed into a chromatographic device and performance is evaluated.
1.26 μm nonporous silica particles (10.4 g), that were previously thermally treated at 600° C. (10 h) and rehydroxylated using 10% nitric acid (Fisher scientific), were dispersed in 100 mL of solvent (water:anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes. Separately, octadecyltrimethylammonium bromide (3.0 g, C18TAB, Sigma-Aldrich) was dissolved in 100 mL of solvent (water:anhydrous ethanol 2:1 v/v). The C18TAB solution was then added into the particle solution and sonicated for 10 minutes. This solution was labeled solution A. In a separate beaker of Pluronic P123 (58.0 g, Sigma-Aldrich) was dissolved in 400 mL of solvent (water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B was added into solution A and allowed to continue sonicate for 20 minutes. The mixture was then transferred into a 1 L round bottom flask and stirred at 750 rpm. Ammonium hydroxide solution (30%, J. T. Baker) was added into the flask and allowed to continue stirring for 5 minutes. A 3.3:1 mol ratio mixture of tetraethoxysilane (TEOS, Sigma-Aldrich) and 1,2-bis(triethoxysilyl)ethane (BTEE, Gelest) was first diluted with anhydrous ethanol (dilution factor=3) and was added to the flask using a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer) at 50 μL/min. Once all the mixture was added the reaction was allowed to continue for 1 h before wash. The wash steps were performed as detailed in Example 28. This process was repeated two more times. The volume of the solution was increased to compensate for the increase in the solids volume maintaining the concentrations of the reagents constant. See Table 23 below for specific reaction conditions. An SEM image of product 76L2 is shown in
The process of Example 76 was modified using a 1.6:1 mol ratio mixture of tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane. See Table 24 below for specific reaction data. An SEM image of product 7712 is shown in
The process of Example 76 was modified using only 1,2-bis(triethoxysilyl)ethane. An SEM image of product 78L2 indicates a 1.55 μm average particle size that is highly aggregated and has increased quantities of fine particles (<1 μm).
Hybrid porous layer, superficially porous particles (3.3 g) prepared following Examples 28-32 were dispersed in a 2 molar solution of hydrochloric acid in acetone. The mixture was mechanically stirred for 18 hours at room temperature. Products were isolated by centrifugation (Forma Scientific Model 5681, 4,000 rpm, 10 min) followed by repeated washes with deionized water until the pH was greater than 6, followed by two methanol washes. Sonication was used between washes to improved dispersion. Products were dried at 80° C. under vacuum for 16 hours and submitted for SEM, and nitrogen sorption analysis. Material data is shown in Table 25. Average particle size was determined by SEM.
Select materials from Examples 76-78 have surfactants removed by acid extraction following the process of Example 79.
Select materials from Examples 79-80 are treated by ozonolysis following the process of Example 41, hydrothermally treated following the process of Example 44, and acid treated as detailed in Example 79, and classification to remove fines and/or agglomerated materials. These materials are reacted with octadecyldimethylchlorosilane and trimethylchlorosilane using the process of Example 65. These Cis-bonded hybrid porous layer superficially porous particles are packed into a chromatographic device and performance is evaluated.
Select unbounded materials from Examples 63, 64, 75, 79-81 have silanol groups surface modified following the process of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423} with reagents including (but not limited to) of the type:
Za(R′)bSi—R,
Preferable silanol surface modification groups include (but are not limited to) octyltrichlorosilane, octadecyltrichlorosilane, octyldimethylchlorosilane, phenylhexyltrichlorosilane, n-butyldimethylchlorosilane, tert-butyldimethylchlorosilane, triisopropylchlorosilane, cyanopropyldiisopropylchlorosilane, pentafluorophenylpropyltrichlorosilane, 2-pyridylethyltrimethoxysilane, and octadecyldimethylchlorosilane
Alternatively, the materials are surface modified by forming an organic covalent bond between surface organic groups and the modifying reagent. Alternatively, the materials are surface modified by coating with a polymer. Alternatively, the materials are modified by a combination of organic group and silanol group modification. Alternatively, the materials are surface modified by a combination of silanol group modification and coating with a polymer. Alternatively, the materials are surface modified by a combination of organic group modification and coating with a polymer. Alternatively, the materials are surface modified by a combination of organic group modification, silanol group modification, and coating with a polymer.
Select unbounded materials from Example 45 (products 45t-45x) are modified with one more or more layers formed using an organosiloxane, a mixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybrid inorganic/organic surrounding material, or combination thereof. These materials have increased hybrid content near the external particle surface.
Select unbounded materials from Example 45 (products 45t-45x) are modified with a hybrid inorganic/organic surrounding material resulting in (SiO2)d/(O1.5SiCH2CH2SiO1.5) where d is 0-30, a hybrid inorganic/organic surrounding material resulting in (SiO2)d/(O1.5SiCH2CH3) where d is 0-30, or combination thereof. These products have increased hybrid content near the external particle surface, and have a 0.01-0.20 cm3/g reduction in porosity with respect to the feed material from Example 45.
One or more tetraalkoxysilanes or organoalkoxysilanes (all from Gelest Inc., Morrisville, PA or United Chemical Technologies, INC., Bristol, PA) or zirconium n-propoxide (70% in propanol, Gelest Inc., Morrisville, PA, 1725 g solution used in reaction 1n) were mixed with ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ) and an aqueous hydrochloric acid solution (Aldrich, Milwaukee, WI) in a flask. Reactions 1a-1r, 1u-1y used 0.1 N HCl, reactions 1s and 1t used 0.01 N HCl, reaction 1z used 0.1 M acetic acid (J. T. Baker). Hydroquinone (Aldrich, Milwaukee, WI) was also added to reaction 1o (8.4 mg) and reaction 1p (17.6 mg) to prevent polymerization of the methacryloxypropyl groups. Product 1y was prepared following a literature protocol (as described in K. Unger, et. Al. Colloid & Polymer Science vol. 253 pp. 658-664 (1975)). The resulting solution was agitated and refluxed for 16 hours in an atmosphere of argon or nitrogen. Alcohol was removed from the flask by distillation at atmospheric pressure. Residual alcohol and volatile species were removed by heating at 95-120° C. for 1-2 hours in a sweeping stream of argon or nitrogen. The resulting polyorganoalkoxy siloxanes were clear viscous liquids. The chemical formulas are listed in Table 1 for the organoalkoxysilanes used to make the product polyorganoalkoxysiloxanes (POS). Specific amounts are listed in Table 2 for the starting materials used to prepare products 1a-1x. Structural analysis was performed using NMR spectroscopy.
To a suspension of 5 μm BEH porous hybrid particles (20 g, Waters Corporation, Milford, MA; 6.5% C; SSA=190 m2/g; SPV=0.80 cm3/g; APD=155 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ; 5 mL/g) was added POS 1a from Example 1. The solvent was slowly removed under reduced pressure in a rotary evaporator for 0.5-4 hours. The particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 20 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (J. T. Baker, Phillipsburg, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 3. The % C values, specific surface areas (SSA), specific pore volumes (SPV) and average pore diameters (APD) of these materials are listed in Table 3.
To a suspension of 5 μm BEH porous hybrid particles (20 g, Waters Corporation, Milford, MA; 6.5% C; SSA=190 m2/g; SPV=0.80 cm3/g; APD=155 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in dry toluene (Fisher Scientific, Fairlawn, NJ; 5 mL/g) was added POS 1a from Example 1 and water. This reaction was heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburgh, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 4. The % C values, specific surface areas (SSA), specific pore volumes (SPV), average pore diameters (APD), and changes in SPV (ΔSPV) are listed in Table 4.
The increase in carbon content (1.0-1.8% C) and reduction in SPV (0.10 cm3/g average change) were observed by this approach. SEM analysis indicated equivalent particle morphology and surface features of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution of the starting particles. This suggests the decreased porosity of this Material Surrounding process is due to a filling of the porous particle framework, and is not due to the introduction of surface debris or a secondary nonporous particle distribution. The reduction in APD also indicates that this Material Surrounding process is filling the pore framework. The slight increase in SSA may indicate the surrounding material has a small degree of porosity.
To a suspension of 3.5 μm BEH porous hybrid particles (Waters Corporation, Milford, MA; 6.5% C; SSA=185 m2/g; SPV=0.76 cm3/g; APD=146 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in dry toluene (Fisher Scientific, Fairlawn, NJ; 5 mL/g for 4a-4b; 10 mL/g for 4e-4i) was added POS 1a from Example 1 and water. This reaction was heated at 80° C. for one hour and 110° C. for 20 hours. Reactions 4a and 4c did not employ the use of a Dean-Stark trap to remove residual water; while the other reactions used of a Dean-Stark trap. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 5. The % C values, specific surface areas (SSA), specific pore volumes (SPV), average pore diameters (APD) and changes in SPV (ASSA) are listed in Table 5.
Increases in carbon content (1.0-2.6% C) and reductions in SPV (0.12-0.44 cm3/g) were achieved by this Material Surrounding approach. SEM analysis confirmed equivalent particle morphology and surface features of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution of the starting particles. This suggests the decreased porosity of this Material Surrounding process is due to a filling of the porous particle framework, and is not due to the introduction of surface debris or a secondary nonporous particle distribution.
As a means to modify the pore structure of surrounded hybrid particles, particles from Examples 3 and 4 were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product was were isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. Specific characterization data for these materials are listed in Table 6. Changes in product % C (Δ% C), SSA (ΔSSA) and APD (ΔAPD), relative to the precursor material from Examples 3 and 4, are listed in Table 6.
This set of experiments showed that hydrothermal processing of surrounded hybrid particles could be used to modify the pore attributes of these materials. All products had noticeable reductions in SSA, increases in APD and no significant changes in SPV or particle morphology (as determined by SEM), when compared with the precursor materials from Examples 3 and 4. It was concluded that the use of hydrothermal treatment was successful in increasing the APD. The APD for these products was within a range that is comparable with commercially available HPLC packing materials. Reductions in % C for these products are due in part to a removal of surface alkoxides and the partial hydrolysis of the methacryloxypropyl group of the surrounding material. This hydrolysis results in the formation of a hydroxypropyl group (e.g., HO(CH2)3SiO1.5), as confirmed by NMR and FT-IR spectroscopy.
To a suspension of porous hybrid particles from Example 5 in dry toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added POS 1a from Example 1 and water. This reaction was heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 7. The % C values, specific surface areas (SSA), specific pore volumes (SPV), average pore diameters (APD), and changes in SPV (ΔSPV) are listed in Table 7.
This set of experiments showed that repeated Material Surrounding can be used to further change the pore properties of these materials. Increases in carbon content (0.7% C) and reduction in SPV (0.13 cm3/g) were achieved with this Material Surrounding approach. Comparing these products with the unmodified BEH particle used in Example 3 and 4, we observe a larger increase in carbon content (1.00-1.36% C) and a decrease in SPV (0.23-0.24 cm3/g) have been achieved by this iterative process. SEM analysis confirmed equivalent particle morphology and surface features of the precursor materials.
Hybrid particles from Examples 6 were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (IRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the products were isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. Specific characterization data for these materials are listed in Table 8. Changes in product % C (A % C), SSA (ΔSSA) and APD (ΔAPD), relative to the precursor material from Example 6, are listed in Table 8.
This set of experiments showed that hydrothermal processing of repeated surrounded hybrid particles could be used reduce the SSA, increase APD and have no significant changes in SPV or particle morphology (as determined by SEM), when compared with the precursor materials. Reductions in % C for these products are due in part to a removal of surface alkoxides of the precursor materials and the partial hydrolysis of the methacryloxypropyl group of the surrounding material. This hydrolysis results in the formation of a hydroxypropyl group (e.g., HO(CH2)3SiO1.5), as confirmed by NMR and FT-IR spectroscopy.
To a suspension of 3.0-3.5 μm BEH porous hybrid particles (20 g, Waters Corporation, Milford, MA; 6.5% C; SSA=185-191 m2/g; SPV=0.76-0.82 cm3/g; APD=146-153 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added a POS from Example 1 (16.42 g) and deionized water (0.8 mL). Reactions 8u, 8v and 8ad used a 4.8 μm BEH porous particle. Reactions 8p and 8q used 8.2 mL of deionized water. Reactions 8s and 8t were performed at a two-fold increased scale, reactions 8w and 8x at ten-fold increased scale, and reaction 8y at 25-fold increased scale. Hydroquinone (30 ppm, Aldrich, Milwaukee, WI) was added to reactions 8n and 8o to prevent polymerization of the methacryloxypropyl group. Reactions were heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. The % C values, specific surface areas (SSA), specific pore volumes (SPV) and average pore diameters (APD) of these materials are listed in Table 9. Changes in product % C (A % C), and SPV (ΔSPV) are listed in Table 9.
This set of experiments showed that a variety of different POS can be used to create hybrid surrounded materials. This series of surrounded materials differ in hydrophobicity and surface activity. For example, the octadecyl groups of surrounded product 8d and partially fluorinated groups of surrounded product 8i may result in increased hydrophobicity over the unmodified BEH particles. The zirconium containing product 8m may display increased surface activity, which may be beneficial for some chromatographic separations. The hydrophobic and strong electron withdrawing nature of the perfluorophenyl containing surrounded product 8t may display both increased hydrophobicity and modified surface silanol activity. As shown with product 8b, the use of a POS with the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 resulted in hybrid surrounded particles that have the sample chemical composition as the unmodified particles, allowing for changes only in particle pore properties.
Carbon content varied due to the composition of the surrounding material. For example, product 8b showed no change in carbon content. This was expected since the surrounding material and the base particle have the same chemical composition. The surrounding material of product 8t, which has a lower carbon content than the BEH material, resulted in a reduction in carbon content of the surrounded product. Products 8u-8y were repeat experiments aimed at determining the reproducibility of this process at increased reaction scale. These products have good reproducibility, having relative standard deviations less than 4.5% for % C, SSA, SPV, and APD data.
Reductions in SPV (−0.04 to −0.25 cm3/g) were also achieved by this Material Surrounding approach. SEM analysis confirmed equivalent particle morphology and surface features of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution to that of the starting particles.
Hybrid particles from Examples 8 were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product was isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. Specific characterization data for these materials are listed in Table 10.
This set of experiments showed that hydrothermal processing of surrounded hybrid particles could be used reduce the SSA, increase APD and have no significant changes in SPV or particle morphology (as determined by SEM), when compared with the precursor materials. While most modifications in % C were small (<0.35% C), larger reductions in % C for some of these products are due in part to a removal of surface alkoxides of the precursor materials and chemical modification of some of specific organofunctional groups of the surrounding material. For example, the partial ester hydrolysis for products 9j, 9n, 9o, 9r and 9s results in the formation of a hydroxypropyl group (e.g., HO(CH2)3SiO1.5). The deprotection of the tert-butoxycarbonyl group for products 9k, 9p and 9q results in the formation of an aminopropyl gre.g., e.g., NH2(CH2)3SiO1.5), as confirmed by NMR spectroscopy.
The modifications in pore structure obtained by hydrothermal treatment of an surrounded hybrid particle can be observed in the nitrogen desorption data (BJH dV/dlog(D) pore volume data). As shown in
To a suspension of 3.5 μm BEH porous hybrid particles (Waters Corporation, Milford, MA; 6.5% C; SSA=185 m2/g; SPV=0.76 cm3/g; APD=146 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in dry toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added POS 1y from Example 1 and deionized water. This reaction was heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 11. The % C values, specific surface areas (SSA), specific pore volumes (SPV) and average pore diameters (APD) of these materials are listed in Table 11. Changes in product % C (A % C) and SPV (ΔSPV) are listed in Table 11.
This set of experiments showed that a tetraalkoxysilane-based POS can be used to create silica surrounded hybrid materials. This may allow for modification of particle surface properties (e.g., silanol activity and hydrophilicity). Carbon content, SSA, SPV and APD decreased as a result of silica Material Surrounding of these hybrid materials, which is due to the lack of carbon in the surrounding material (e.g., SiO2). SEM analysis confirmed equivalent particle morphology and surface features of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution of the starting particles.
Hybrid particles from Example 10 were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product was isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. Specific characterization data for these materials are listed in Table 12.
This set of experiments showed that hydrothermal processing of silica surrounded hybrid particles could be used reduce the SSA, increase APD and have no significant changes in % C, SPV or particle morphology (as determined by SEM) when compared with the precursor materials.
Diamond nanoparticles (Nanostructured & Amorphous Materials, Inc, Houston, TX, 4-25 nm) or silicon carbide nanoparticles (Sigma-Aldrich, Saint Louis, MO, <100 nm) were added to POS 1c in Example 1 to yield a 0.1-0.2 wt % dispersion. Dispersion was achieved using a rotor/stator mixer (Mega Sheer, Charles Ross & Son Co., Hauppauge, NY). Products were then centrifuged (Thermo EXD, 4×1 L bottle centrifuge, Milford, MA) to reduce agglomerates. Specific amounts are listed in Table 13 for the starting materials used to prepare these products.
To a suspension of 3.5 μm BEH porous hybrid particles (20 g, Waters Corporation, Milford, MA; 6.5% C; SSA=185 m2/g; SPV=0.76 cm3/g; APD=146 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added a POS from Example 12 (16.42 g) and deionized water (0.8 g). This reaction was heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. The % C values, specific surface areas (SSA), specific pore volumes (SPV), average pore diameters (APD) and changes in SPV (ΔSPV) of these materials are listed in Table 14.
This set of experiments showed that a nanoparticle containing POS can be used to create composite surrounding materials. This may allow for modification of particle properties (e.g., surface acidity, thermal and mechanical properties). A reduction in SPV (0.11 cm3/g) was achieved by this composite Material Surrounding approach. SEM analysis confirmed equivalent particle morphology and surface features to that of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution of the starting particles. This suggests the decreased porosity of this Material Surrounding process is due to a filling of the porous particle framework, and is not due to the introduction of surface debris or secondary nonporous particles.
Hybrid particles from Examples 13b were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product was isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. The resulting product 14a had 6.49% C, a specific surface area (SSA) of 132 m2/g, a specific pore volume of 0.64 cm3/g, and an average pore diameter (APD) of 167 Å. Hydrothermal processing of a composite surrounded hybrid material reduced SSA and increased APD without having a significant changes in SPV or particle morphology (as determined by SEM) when compared with the precursor materials.
To a suspension of wider pore BEH porous hybrid particles of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) denoted Type A (3.5 μm; 6.3% C; SSA=38 m2/g; SPV=0.67 cm3/g; APD=600 Å; MPV=0.67 cm3/g; MPD=513 Å), Type B (3.5 μm; 6.6% C; SSA=83 m2/g; SPV=0.65 cm3/g; APD=287 Å; MPV=0.61 cm3/g; MPD=243 Å), or Type C (5 μm; 6.44% C; SSA=95-100 m2/g; SPV=0.81-0.83 cm3/g; APD=289-324 Å; MPV=0.77-0.83 cm3/g; MPD=252-265 Å) in toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added a POS from Example 1 and deionized water. Reactions were heated at 80° C. for one hour and 110° C. for 20 hours. For reactions 15a and 15b a Dean-Stark trap was used to remove residual water. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. The % C values and specific surface areas (SSA) of these materials are listed in Table 15. The median mesopore diameter (MPD) and mesopore pore volume (MPV), measured by Mercury Porosimetry are listed in Table 15. Changes in product SPV (ΔSPV) and MPV (ΔMPV), relative to the unmodified hybrid particles, are listed in Table 15.
This set of experiments showed that a hybrid POS can be used to create surrounded wider pore diameter hybrid materials. This may allow for modification of particle surface properties, and mechanical properties. A reduction in pore volume may allow for improvements in mechanical strength of the porous network. Reduction in MPV (0.06-0.16 cm3/g) were achieved by this composite Material Surrounding approach. SEM analysis confirmed equivalent particle morphology and surface features of the starting particles. Particle size analysis (by Coulter Counter) indicated equivalent particle size and distribution to that of the starting particles.
Hybrid particles from Examples 15 were mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a slurry concentration of 5 mL/g. The pH of the resultant slurry was adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The slurry was then enclosed in a stainless steel autoclave and heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product was isolated on 0.5 μm filtration paper and washed with water and methanol (Fisher Scientific, Suwanee, GA). The particles were then dried at 80° C. under vacuum for 16 hours. Specific characterization data for these materials are listed in Table 16. Hydrothermal processing of a surrounding material with wider pore hybrid material reduced SSA and increased MPD without a significant changes in % C or particle morphology (as determined by SEM) when compared with the precursor materials. A high resolution SEM of product 16a indicates that a highly porous pore network is maintained by this process.
Porous particles prepared according to Examples 5, 9 and 11 were dispersed in a 1 molar hydrochloric acid solution (Aldrich, Milwaukee, WI) for 20 h at 98° C. The particles were isolated on 0.5 μm filtration paper and washed with water to a neutral pH, followed by acetone (HPLC grade, Fisher Scientific, Fairlawn, N.J.). The particles were dried at 80° C. under vacuum for 16 h. Specific characterization data for these materials are listed in Table 17.
While no significant changes in SSA, SPV or APD occurred with respect to the precursor materials, there are noticeable reductions in SSA (reduced 13-63 m2/g) and SPV (reduced 0.05-0.23 cm3/g) with respect to the unmodified BEH hybrid particles.
With the exception of product 17k and 171, no significant changes in % C occurred with respect to the precursor materials. The loss in % C for these two products (reduced 0.41-0.75% C) may have resulted in deprotection of remaining tert-butoxycarbonyl groups, resulting in the formation of an aminopropyl group (e.g., NH2(CH2)3SiO1.5). Changes in % C, with respect to the unmodified BEH hybrid increased or decmased due to the chemical formula of the surrounding material. The micropore surface area (MSA) for these materials are all within the requirement for chromatographic material having chromatographically enhanced pore geometry. Repeat experiments, products 17t-17x, demonstrate good reproducibility with relative standard deviations for % C, SSA, SPV, and APD less than 5%.
Hydroxypropyl containing Hybrid particles with a surrounding material from Example 17 were modified with octadecyl isocyanate (ODIC, Aldrich Chemical), dodecyl isocyanate (DIC, Aldrich Chemical), pentafluorophenyl isocyanate (PFPIC, Aldrich Chemical), 1-adamantly isocyanate (AIC, Aldrich Chemical), 4-cyanophenyl isocyanate (4CPIC, Aldrich Chemical), 3-cyanophenyl isocyanate (3CPIC, Aldrich Chemical), 4-biphenylyl isocyanate (BPIC, Aldrich Chemical), 2,2-Diphenylethyl isocyanate (DPEIC, Aldrich Chemical), 3,5-dimethoxyphenyl isocyanate (DMPIC, Aldrich Chemical), 4-iodophenyl isocyanate (IPIC, Aldrich Chemical), 4-(chloromethyl)phenyl isocyanate (CMPIC, Aldrich Chemical), methyl (S)-(−)-2-isocyanato-3-phenylpropionate (MIP, Aldrich, Milwaukee, WI), phenyl isocyanate (PIC, Aldrich Chemical), benzyl isocyanate (BIC, Aldrich Chemical), or phenethyl isocyanate (PEIC, Aldrich Chemical) in dry toluene (5 mL/g, J. T. Baker) under an argon blanket. The suspension was heated to reflux (110° C.) for 16 h and then cooled to <30° C. Product 18g was prepared in refluxing xylenes (30 mL/g, J. T. Baker). The particles were transferred to a filter apparatus and washed exhaustively with toluene and acetone. The material was then heated for an hour at 50° C. in a 1:1 v/v mixture of acetone and 1% trifluoroacetic acid (Aldrich, Milwaukee, WI) solution (10 mL/g particles, Hydrolysis type A), or in a 60:40 v/v mixture of acetone and 100 mM ammonium bicarbonate (pH 8, Aldrich, Milwaukee, WI) for 20 hours (Hydrolysis type B), or in a 60:40 v/v mixture of acetone and 100 mM ammonium bicarbonate (pH 10, Aldrich, Milwaukee, WI) for 20 hours (Hydrolysis type C). Product 18r was heated for 1 hour. The reaction was then cooled and the product was filtered and washed successively with acetone and toluene (heated at 70° C.). The product was then dried at 70° C. under reduced pressure for 16 hours. Reaction data is listed in Table 18. The surface coverage of carbamate groups was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
The material of Example 18 were further modified with octadecyl isocyanate (ODIC, Aldrich Chemical), t-butyl isocyanate (TBIC, Aldrich Chemical), or n-butyl isocyanate (NBIC, Aldrich Chemical) in dry toluene (5 mL/g, J. T. Baker) under similar reaction conditions as Example 18. Reaction data is listed in Table 19. The additional surface coverage of carbamate groups was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
The materials of Example 18 and 19 were further modified with either trimethylchlorosilane (TMCS, Gelest Inc., Morrisville, PA), triethylchlorosilane (TECS, Gelest Inc., Morrisville, PA), triisopropylchlorosilane (TIPCS, Gelest Inc., Morrisville, PA), thexyldimethylchlorosilane (TDMCS, Gelest Inc., Morrisville, PA), tert-butyldimethylchlorosilane (TBDMCS, Gelest Inc., Morrisville, PA), 1-(tert-Butyldimethylsilyl)imidazole (TBDMSI, TCI America), or tert-butyldiphenylchlorosilane (TBDPCS, Gelest Inc., Morrisville, PA) using imidazole (Aldrich, Milwaukee, WI) in refluxing toluene (5 mL/g) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water, toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker) and then dried at 80° C. under reduced pressure for 16 hours. Product 20f was performed for 20 hours. Products 20f, 20i, 20j, 20k, and 20l underwent a subsequent reaction with TMCS under similar reaction conditions. Reaction data are listed in Table 20.
Samples from Example 17 were modified with octadecyltrichlorosilane (OTCS, Aldrich, Milwaukee, WI) or octadecyldimethylchlorosilane (ODMCS, Gelest Inc., Morrisville, PA) using imidazole (Aldrich, Milwaukee, WI) in refluxing toluene (HPLC grade, Fisher Scientific, Fairlawn, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker). For product 21a, the material was then refluxed in an acetone/aqueous 0.12 M ammonium acetate solution (Sigma Chemical Co., St. Louis, MO) for 2 hours. The reaction was then cooled and the product was filtered and washed successively with toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker). The product was then dried at 80° C. under reduced pressure for 16 hours. Reaction data is listed in Table 21. The surface coverage of C18-groups was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
The surface of the C1-bonded hybrid material of Example 21a (14 g) was further modified with triethylchlorosilane (2.76 g, TECS, Gelest Inc., Morrisville, PA) using imidazole (1.50 g, Aldrich, Milwaukee, WI) in refluxing toluene (75 mL) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water, toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker) and then dried at 80° C. under reduced pressure for 16 hours. The materials were then mixed with hexamethyldisilazane (HMDS, Gelest Inc., Morrisville, PA) yielding a slurry (concentration 1.1 g HMDS per 1.0 g particles). The resultant slurry was then enclosed in a stainless steel autoclave and heated at 200° C. for 18 hours. After the autoclave cooled to room temperature the product was isolated on filtration paper and washed successively with water, toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker) and then dried at 80° C. under reduced pressure for 16 hours. The product (22a) had 14.04% C.
The surface of the hybrid particle with a surrounding material from Examples 17 and 21 were modified with trimethylchlorosilane (TMCS, Gelest Inc., Morrisville, PA) using imidazole (Aldrich, Milwaukee, WI) in refluxing toluene for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water, toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker) and then dried at 80° C. under reduced pressure for 16 hours. Reaction data are listed in Table 22.
To a suspension of 3.5 μm BEH porous hybrid particles (20 g, Waters Corporation, Milford, MA; 6.5% C; SSA=188 m2/g; SPV=0.78 cm3/g; APD=150 Å) of the formula (O1.5SiCH2CH2SiO15)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in toluene (Fisher Scientific, Fairlawn, NJ; 10 mL/g) was added a dispersion of <0.5 μm BEH porous hybrid particles within POS 1c from Example 1, and water (0.82 mL). The dispersion of <0.5 μm BEH porous hybrid particles (particle size determined by SEM) within POS 1c was achieved for examples 24a and 24b by stirring overnight. The dispersion for example 24c required initial dilution in ethanol, followed by vacuum distillation of ethanol. This Material Surrounding reaction was heated at 80° C. for one hour and 110° C. for 20 hours. The reaction was cooled to room temperature and particles were isolated on 0.5 μm filtration paper and washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ). The material was then heated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product was then dried at 80° C. under reduced pressure for 16 hours. Specific amounts of starting materials used to prepare these products are listed in Table 23. The % C values, specific surface areas (SSA), specific pore volumes (SPV), average pore diameters (APD) and change in SPV (ΔSPV) of these materials are listed in Table 23. SEM analysis indicated the presence of surface<0.5 μm particulates on the 3.5 μm particles.
To a suspension of BEH porous hybrid particles (Type A, Waters Corporation, Milford, MA; 6.5% C; SSA=190 m2/g; SPV=0.80 cm3/g; APD=155 Å) or 3 μm wider pore BEH porous particles (Type B, Waters Corporation, Milford, MA; 6.5% C; SSA=88 m2/g; SPV=0.68 cm3/g; APD=285 Å) of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (prepared following the method described in U.S. Pat. No. 6,686,035) in toluene (HPLC grade, Fisher Scientific, Fairlawn, NJ) were modified with 3-acetoxypropyltrichlorosilane (ATPTCS, Silar Laboratories, Scotia, NY) and imidazole (Aldrich, Milwaukee, WI) and deionized water in refluxing toluene (HPLC grade, Fisher Scientific, Fairlawn, NJ) for 20 hours. Reaction 25a used 5 μm particles, and Reactions 25g and 25h used 3.5 μm particles. The reaction was then cooled and the material was filtered and washed successively with toluene, 1:1 v/v acetone/water and acetone (all solvents from Fisher Scientific, Fairlawn, NJ). The material was then refluxed in an acetone/aqueous 0.12 M ammonium acetate solution (Sigma Chemical Co., St. Louis, MO) for 2 hours. The reaction was then cooled and the product was filtered and washed successively with toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker). The product was then dried at 80° C. under reduced pressure for 16 hours. The material was then dispersed in a 1 molar hydrochloric acid solution (Aldrich, Milwaukee, WI) for 20 h at 98-100° C. to yield hydroxypropyl groups (e.g., HO(CH2)3SiO1.5), as confirmed by NMR spectroscopy. The particles were isolated on 0.5 μm filtration paper and washed with water to a neutral pH, followed by acetone (HPLC grade, Fisher Scientific, Fairlawn, NJ). The particles were dried at 80° C. under vacuum for 16 h. Reaction data is listed in Table 24. Product 25h was also hydrothermally treated following the procedure in Experiment 9, and was acid treated following the procedure in Experiment 17. The surface coverage of hydroxypropyl groups was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
Particles from Example 25a (20 g) were modified with octadecyl isocyanate (9.99 g, Aldrich Chemical) in dry toluene (100 mL, Fisher Scientific, Fairlawn, NJ) under an argon blanket. The suspension was heated to reflux (110° C.) for 16 h and then cooled to <30° C. The particles were transferred to a filter apparatus and washed exhaustively with toluene and acetone. The material was then heated for an hour at 50° C. in a 1:1 v/v mixture of acetone and 1% trifluoroacetic acid (Aldrich, Milwaukee, WI) solution (100 mL). The reaction was then cooled and the product was filtered and washed successively with acetone and toluene (heated at 70° C.). The material was then dried at 70° C. under reduced pressure for 16 hours. The carbon content of this material was 13.32% C, and the surface coverage of carbamate groups was 1.73 μmol/m2, determined by the difference in % C before and after the surface modification as measured by elemental analysis. The surface of these particles were modified with trimethylchlorosilane (TMCS, Gelest Inc., Morrisville, PA) using imidazole (Aldrich, Milwaukee, WI) in refluxing toluene for 4 hours. The reaction was then cooled and the product was filtered and washed successively with water, toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker) and then dried at 80° C. under reduced pressure for 16 hours. The final carbon content of the product (26a) was 14.24% C.
Samples of porous particles from Example 18, 20, 23 and 26 were used for the separation of a mixture of neutral, polar and basic compounds listed in Table 25. The 2.1×100 mm chromatographic columns were packed using a slurry packing technique. The chromatographic system consisted of an ACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2 Chromatography Data Software (Build 2154) was used for data collection and analysis. Mobile phase conditions were: 20 mM K2HPO4/KH2PO4, pH 7.00±0.02/methanol (36/65 v/v); flow rate: 0.25 mL/min; temperature: 23.4° C.; detection: 254 nm.
It can be seen that these porous hybrid particles with a surrounding material provide sufficient retention and resolution in the separation of neutral, polar, and basic compounds. Relative retention is the retention time of the analyte divided by the retention time of acenaphthene. Therefore values less than one, indicate less retention than acenaphthene, and values greater than one, indicate more retention than acenaphthene. (Relative retention is a well known parameter in the field of HPLC.)
Samples of porous particles from Example 18, 20, 23 and 26 were evaluated for USP peak tailing factors using the mobile phase and test conditions of Example 25. The results are shown in Table 26. Peak tailing factors is a well known parameter in the field of HPLC (a lower value corresponds to reduced tailing). It is evident that the peak tailing factors these porous hybrid particles having a surrounding material have comparable basic compound tailing factors of commercially available Cis-columns.
Samples of porous particles from Example 9 and 17 were used for the separation of a mixture of neutral, polar and basic compounds listed in Table 27. The 2.1×100 mm chromatographic columns were packed using a slurry packing technique. The chromatographic system consisted of an ACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2 Chromatography Data Software (Build 2154) was used for data collection and analysis. Mobile phase conditions were: 100 mM ammonium formate, pH 0.3.00±0.02/acetonitrile (10/90 v/v); flow rate: 0.5 mL/min; temperature: 23.4° C.; detection 254 nm.
It can be seen that these porous hybrid particles provide sufficient retention and resolution in the separation of polar compound under Hydrophilic Interaction Chromatography (HILIC) test conditions. Relative retention is the retention time of the analyte divided by the retention time of thymine. Therefore, values less than one, indicate less retention than thymine, and values greater than one, indicate more retention than acenaphthene. (Relative retention is a well known parameter in the field of HPLC) t-Boc protected aminopropyl hybrid particles having a surrounding material, 9q, showed low retention times for all analytes under these test conditions. This is expected due to the increased hydrophobicity of the t-Boc group. The deprotected aminopropyl surrounding hybrid particles, 171, resulted in a significant increase in retentivity.
Samples of porous particles from Example 9 and 17 were evaluated for USP peak tailing factors using the mobile phase and test conditions of Example 27. The results are shown in Table 28. Peak tailing factor is a well known parameter in the field of HPLC (a lower value corresponds to reduced tailing). It is evident that the porous hybrid particles having a surrounding material have comparable basic compound tailing factors of commercially available Hydrophilic Interaction Chromatography (HILIC) columns.
Surface derivatized hybrid porous particles from Examples 18, 20 and 26 as well as selected commercial columns (C18 Type) based on silica, which have similar alkyl silyl groups, were evaluated for stability in acidic mobile phases using the following procedure. Columns were prepared by slurry packing the materials into 2.1×50 mm steel columns and were tested on the following instrument configuration: Waters ACQUITY UPLC™ system was used for solvent delivery, sample injection (1 μL on a 5 μL loop using partial loop injection), UV detection (500 nL flow cell, Absorbance: 254 nm) and column heating at 60° C. Analysis conditions were as follows: 1) the retention time was measured for a test analyte, methyl paraben (100 μg/mL sample); 2) mobile phase conditions were 0.5% aqueous TFA at a flow of 1.4 mL/min and a column temperature of 60° C.; and 3) 20 minute run times for 61 repeated injections under the same isocratic test conditions were used. The percent changes in the retention time are reported for final injections for methyl paraben, with respect to the retention obtained on the third injection. The results are shown in Table 29.
It is evident that the lifetimes of most of the columns containing hybrid particles having a surrounding material had similar chemical stability with respect to commercial columns containing silica-based materials (lower percent loss in original retention for each injection corresponds to improved chemical stability).
The hydrolytic stability of the columns packed with porous hybrid particles from Example 17, 18, 20, 22, and 26 as well as some comparison columns were evaluated using the following procedure. Columns (3×30 mm) were equilibrated in 1:1 acetonitrile/water (210 minutes) before initial chromatographic performance was tested using uracil and decanophenone (1:1 acetonitrile/water; 0.43 mL/min). The columns were then heated at 50° C. and were challenged with a solution of 0.02 N NaOH in water (pH 12.3, 0.85 mL/min for 60 min) before flushing with 10:90 methanol/water followed by methanol. Chromatographic performance was reassessed at regular intervals by equilibrating the columns with acetonitrile (50 minutes), followed by testing using uracil and decanophenone (1:1 acetonitrile/water or 0.1% formic acid in 30:70 methanol/water, 0.43 mL/min). This process was repeated and the performance of the column was monitored until column failure. Column failure is defined as the time when the plate number drops to 50% of the initial value or when the test system shut down due to high column pressure. The results of these tests, including final reported loss in original column efficiency are shown in Table 30. Comparison Column A was commercially available 5 μm porous hybrid particles of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4, that was surface modified with C18H37SiCl3 followed by endcapping. Comparison Column B (repeated on three separate columns) was 3.5 μm porous hybrid particles of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4, that was surface modified with CH3(CH2)11NHCO2(CH2)3Si(CH3)2Cl followed by endcapping. Comparison Column C was a commercially available 3 μm silica-core particle that was surface modified with an organofunctional silane followed by C18 surface modification. Comparison Column D was commercially available 5 μm porous hybrid particles of the formula (CH3SiO1.5)(SiO2)2, that was surface modified with C18H37SiCl3 followed by endcapping. Comparison Column E was commercially available 5 μm porous silica particles that was surface modified with C18H37Si(CH3)2Cl followed by endcapping.
Comparison Column A and B (which is based on a hybrid formula that is substantially enriched in silica content) failed under these test conditions between 22-52 hours exposure to 0.02 N NaOH. Hybrid Column E failed within 3 hours exposure to 0.02 N NaOH. Comparison Column C and E (which are based on a silica base particle) failed under these test conditions at 3-5 hours exposure to 0.02 N NaOH. It is well known in the field of HPLC that column failure resulting in high column pressure when silica based columns are exposed to alkaline solutions can result from the dissolution of the silica particle resulting in the collapse of the column bed. For Comparison Column B this packed-bed collapse was confirmed by column dissection and the measurement of a 10 mm void at the inlet of the column.
It can be concluded that the durability of the porous hybrid packing materials from Example 17, 20 and 22 are improved over the both Comparison Columns C, D, and E, and are comparable to Comparison Columns A and B under these test conditions.
Chromatographic selectivity differences for select products from Example 18 and 20 were evaluated under pH 7 and pH 3 test conditions (2.1×100 mm columns). System conditions were the same as detailed in Experiment 27. Mobile phase conditions were: 20 mM K2HPO4/KH2PO4, pH 7.00±0.02/methanol (36/65 v/v) or 15.4 mM ammonium formate, pH 3.0/acetonitrile (65/35 v/v); flow rate: 0.25 mL/min, temperature: 23° C.; detection: 254 nm. pH 7 test molecules included uracil, propranolol, butylparaben, naphthalene, dipropylphthalate, acenaphthene, and amitriptyline. pH 3 test molecules included uracil, pyrenesulfonic acid, desipramine, amitriptyline, butylparaben, and toluene. The correlation coefficient (R2) for retention times were made with a commercially available C18 column (XBridge C18, Waters Corporation) under both pH 7 and pH 3 test conditions. The selectivity value was calculated by 100(1−R2)0.5 as shown in Table 31. A lower R2 and higher Selectivity Value indicate a greater selectivity difference under these test conditions. It can be concluded that surface modification of hybrid particles under conditions used in Examples 18 and 20 provide a different chromatographic selectivity under these test conditions.
Chloromethylphenyl containing particles 18w from Experiment 18 were further modified with piperazine (Acros, Geel Belgium) in refluxing toluene (110° C., HPLC grade, Fisher Scientific, Fairlawn, NJ) for 20 hours. The reaction was then cooled and the material was filtered and washed successively with toluene, 1:1 v/v acetone/water and acetone (all solvents from J. T. Baker). The product was then dried at 80° C. under reduced pressure for 16 hours. Reaction data is listed in Table 32. The surface coverage of piperazyl groups (e.g., O1.5Si(CH2)3OC(O)NHC6H4CH2N(CH2CH2)2NH) was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
Propanol containing hybrid particles from Example 17 were modified with 1,1′-carbonyldiimidazole (CDI, Fluka, Buchs, Switzerland) in toluene (Tol, 5 mL/g, Fisher Scientific, Fairlawn, NJ) for 2 hours at room temperature, or in dimethylformamide (DMF, 5 mL/g, Aldrich) for 20 hours at room temperature. Reactions performed in toluene were transferred to a filter apparatus and washed exhaustively with toluene, before redispersing in toluene. Octadecylamine (ODA, Fluka), octylamine (OA, Aldrich), 4-aminophenol (AP, Aldrich), tris(hydroxymethyl)methylamine (TRIS, Aldrich, dissolved in DMF at 60° C.), or pentafluorophenylamine (PFPA, Aldrich) was then added and the reaction was stirred for an additional 20 hours. Specific reaction conditions are provided in Table 33. The product was filtered and washed successively with acetone, toluene, water and/or DMF. The material was then dried at 70° C. under reduced pressure for 16 hours. Product 35b and 35c were further heated for an hour at 50° C. in a 1:1 v/v mixture of acetone and 1% trifluoroacetic acid (Aldrich, Milwaukee, WI) solution (10 mL/g particles), and products 35f and 35g were further heated for 20 hours at 50° C. in a 60:40 v/v mixture of acetone and 100 mM ammonium bicarbonate (pH 8, Aldrich, Milwaukee, WI). The reaction was then cooled and the product was filtered and washed successively with acetone and toluene (heated at 70° C.). The product was then dried at 70° C. under reduced pressure for 16 hours. Product data is listed in Table 33. Product 35e was obtained by repeating this process on product 35d. The surface coverage of carbamate groups was determined by the difference in particle % C before and after the surface modification as measured by elemental analysis.
Hybrid inorganic/organic monoliths of the formula (O1.5SiCH2CH2SiO1.5)(SiO2)4 (which is prepared following the method described in U.S. Pat. No. 7,250,214) are soaked in toluene (J. T. Baker, 20 mL/g) and refluxed for 3.5 hours under an argon atmosphere to deoxygenate and to remove adsorbed water via azeotropic distillation. After cooling to room temperature under, POS 1c from Example 1 (0.8-1.6 g/g) and deionized water (0.04-0.2 mL/g) is added. The reaction is heated at 80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap to remove residual water. Alternatively the Dean-Stark trap is not employed to remove residual water from the reaction. The reaction is cooled to room temperature and monoliths are washed repeatedly using ethanol (anhydrous, J. T. Baker, Phillipsburg, NJ).
The material is then heated at 50° C. in a suspension with ethanol (3 mL/g, anhydrous, J. T. Baker, Phillipsburg, NJ), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J. T. Baker, Phillipsburg, NJ) for 4 hours. The reaction is then cooled and the product is washed successively with water and methanol (Fisher Scientific, Fairlawn, NJ). The product is dried at 80° C. under reduced pressure for 16 hours.
This Material Surrounding of hybrid inorganic/organic monoliths can be performed using a variety of hybrid inorganic/organic POS' from Example 1 (1a-1x), nanoparticle containing POS from Example 12, or sub-1 μm particle containing POS as detailed in Example 24. Silica hybrid monoliths with a surrounding material can also be prepared using POS 1y from Example 1. This Material Surrounding of hybrid inorganic/organic monoliths can be performed in a reactor, or within a chromatographic device (e.g., microbore tubes, extraction cartridges, capillary tubes) under a pressurized flow of solvent and reagents, or it can be performed under stop-flow conditions. This Material Surrounding can be performed using a variety of hybrid monoliths, including other hybrid monoliths detailed in U.S. Pat. No. 7,250,214, hybrid monoliths prepared from the condensation of one or more monomers that contain 0-99 mole percent silica (e.g., SiO2), hybrid monoliths prepared from coalesced porous inorganic/organic particles (also detailed in U.S. Pat. No. 7,250,214), hybrid monoliths that have a chromatographically-enhancing pore geometry, hybrid monoliths that do not have a chromatographically-enhancing pore geometry, hybrid monoliths that have ordered pore structure, hybrid monoliths that have non-periodic pore structure, hybrid monoliths that have non-crystalline or amorphous molecular ordering, hybrid monoliths that have crystalline domains or regions, hybrid monoliths with a variety of different macropore and mesopore properties, and hybrid monoliths in a variety of different aspect ratios.
Hybrid inorganic/organic particles having a surrounding material from Examples 8-11 and Examples 13-24 are mixed with 5 μm Symmetry silica (Waters Corporation, 0-50% weight) to yield 6 g total mass. The mixture is dispersed in an appropriate solvent (e.g., isopropanol/tetrahydrofuran mixtures) for 5 minutes, before slurry packing into 2.1×50 mm HPLC columns using a downward slurry technique with a high-pressure liquid packing pump. After completion of column packing, the pressure is released and the end fitted column is transferred to chromatographic pump station (Waters 590 HPLC pump or equivalent), whereupon the column is purged with dry toluene (J. T. Baker, 0.2 mL/min), before pumping (0.2 mL/min) a solution of POS 1c from Example 1 (0.8 g per gram of particle mixture) and water (0.04 mL per gram of particle mixture) that is pre-diluted in toluene. These reactions can use short (less than 1 hour) or extended flow times (less than 72 hours) to aid in monolith formation. The column pressure is allowed to drop for 30 minutes prior to disconnection. The columns are left uncapped in a chemical fume hood's air stream for 5-18 hours, transferred to a 65° C. convection oven for 28 hours and then cooled to room temperature. Analysis of these hybrid monoliths (SSA, SPV, APD, % C, SEM, mercury porosimetry) is performed on samples that are extruded from the columns and are vacuum dried for a minimum of 8 hours at room temperature.
This monolith formation of hybrid inorganic/organic particles is performed using a variety of hybrid inorganic/organic POS from Example 1 (1a-1x), nanoparticle containing POS from Example 12, or sub-1 μm particle containing POS as detailed in Example 24. To increase the macropore volume of this monolith, the silica template may be removed through purging the column with solutions of aqueous sodium hydroxide or trimethyl amine. Alternatively, the silica particle may be replaced with appropriately sized polystyrene latex. For this alternative monolith system, solvents that do not swell or dissolve the polystyrene latex must be employed (e.g., a polar protic solvent, or the pumping of a POS from Example 1 with or without additional water present). Upon formation of the coalesced hybrid particle monolith, the polystyrene particles can be removed thermally or by purging the column with toluene. Thermal removal of polystyrene can be aided with an inert atmosphere purge (nitrogen or argon) or the use of vacuum.
A monolith from Examples 36 or 37 is mixed with an aqueous solution of 0.3 M tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical, Milwaukee, WI) at a concentration of 5 mL/g, and the pH is adjusted to 9.8 using acetic acid (J. T. Baker, Phillipsburg, NJ). The monolith is enclosed in a stainless steel autoclave and is heated to 155° C. for 20 hours. After cooling the autoclave to room temperature, the product is washed with water and methanol (Fisher Scientific, Suwanee, GA), and is dried at 80° C. under vacuum for 16 hours. Products prepared in this manner have chromatographically enhanced pore geometry.
A monolith from Examples 36, 37 or 38 is treated with a 1 molar hydrochloric acid solution (Aldrich, Milwaukee, WI) for 20 h at 98° C. After cooling the product is washed with water to a neutral pH, followed by acetone (HPLC grade, Fisher Scientific, Fairlawn, N.J.). The monolith is dried at 80° C. under vacuum for 16 h. Surface silanol groups of these surrounded hybrid monoliths can be modified in a similar manner as shown in Examples 20-22 by reaction with chlorosilanes. Hybrid monoliths containing surface hydroxypropyl groups can be modified in a similar manner as shown in Example 18-19 by reaction with isocyanates. Other transformations of synthetically relevant hybrid groups have been reported in U.S. Pat. No. 7,250,214. Chromatographic evaluation of surface modified hybrid monoliths having a surrounding material prepared in chromatographic columns can be performed in a similar manner as detailed in Examples 27-30. Chemical stability tests can also be performed as detailed in Examples 31-32.
Following the procedure in Example 26, products 25g and 25h were reacted with octadecyl isocyanate, followed by endcapping with trimethylchlorosilane. Product data is shown in Table 34.
Following the general procedure in Example 26, product 25a-h reacts with 4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, or 2-cyanophenyl isocyanate. Hydrolysis type A, B, or C from Example 18 is preformed. Products prepared by this manner can be endcapped or used without any further transformation.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by this invention.
All publications, patent applications and patents identified herein are expressly incorporated herein by reference in their entireties.
This application is a continuation of U.S. application Ser. No. 16/082,803 filed Sep. 6, 2018, which is a national phase of International Patent Application No. PCT/US2017/020907, filed Mar. 6, 2017, which claims the benefit of and priority to U.S. Provisional Application No. 62/304,261 filed Mar. 6, 2016, U.S. Provisional Application No. 62/304,259 filed Mar. 6, 2016, and U.S. Provisional Application No. 62/304,254 filed Mar. 6, 2016, the disclosures of which are herein incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62304261 | Mar 2016 | US | |
| 62304259 | Mar 2016 | US | |
| 62304254 | Mar 2016 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16082803 | Sep 2018 | US |
| Child | 18311671 | US |
