Patent Application
20200230571
Although liquid chromatographic stationary phases and solid phase extraction sorbents enjoy a combined global multi-billion-dollar market, the technology of preparing these materials is still evolving. The instrument hardware and the software controlling chromatographic analysis have experienced tremendous improvements, such as faster data collection rate, minimal instrument breakdown, and steady operational performance, the heart of the system is the liquid chromatographic stationary phases (for separation) and solid phase extraction sorbents (for sample preparation). These materials suffer from a number of shortcomings that include low carbon loading, limited pH stability, poor thermal stability, relatively low surface area, and low average pore width. As a result, the separation capacity in liquid chromatography is still limited compared to gas chromatography. This inherent shortcoming has been addressed by a number of ways, such as ultra-performance liquid chromatography with smaller particle size. However, that approach is limited as it continues to use the same stationary phase synthesis strategy as the larger particle material.
State-of-the-art in synthesizing silica based liquid chromatographic stationary phases and solid phase sorbents traditionally employ spherical solid silica particles as the substrate on the surface upon which a thin layer of stationary phase coating of C8/C18/phenyl/cyano/diol ligands that are grafted via different immobilization techniques. These surface grafting and immobilization processes do not allow high loading of the stationary phases or extraction sorbents on the substrate, generally 10-18% C loadings with the substrate occupying about 80 to 90% the mass of the stationary phases and solid phase extraction sorbents, which limits mass loading of the stationary phases and solid phase extraction sorbents and the separation power of liquid chromatography and the sample capacity of solid phase extraction therefrom.
A nearly exponential growth of the applications of mesoporous silica has occurred in many fields including catalysis, biomedicine, adsorption, column chromatography, drug delivery, and sensors. The development of new strategies for synthesizing mesoporous silica remains a strong research target among materials chemist. Among the many different approaches in synthesizing mesoporous silica, base catalyzed sol-gel reactions using tetraethyl orthosilicate (TEOS) as the inorganic precursor and NH4OH as the base catalyst are the most common, with sacrificial templates such as polyethylene glycol, block copolymers, and nonionic surfactants used as porogenic agents for ultimate removal by calcination of these sol-gel materials to yield mesoporous silica.
Sol-gel processes are typically carried out with concurrent hydrolysis and condensation processes. When an acid catalyst, such as hydrochloric acid (HCl), trifluoroacetic acid (TFA), or acetic acid, is used hydrolysis proceeds faster than condensation, which results in an open and linear network with relatively little branching. Solvent and sacrificial templates are trapped in the open spaces of the network. As such, removal of solvent and sacrificial templates does not contribute to creation of mesopores. When a base catalyst is used, condensation proceeds rapidly from hydrolyzed functionality and results rapid nucleation and a highly branched particle-like morphology. The particle-like units are very dense and rigidly encapsulate solvents and porogenic templates such that, when the templates are removed by calcination, distinct mesopores in the sol-gel matrix are formed.
An acid catalyzed followed by base catalyzed sol-gel process has been described in Kabir et al., U.S. Pat. Nos. 9,925,515, 9,925,518, and U.S. patent application Ser. No. 15/818,836. The synthesis of mesoporous silica particles using this dual catalyst approach using an acid catalyst for hydrolysis and a base and/or fluoride catalyst for the polycondensation has not been reported. To this end, the formation of mesoporous silica in this manner is of interest toward the formation of superior mesoporous silica particles, and their applications for liquid chromatographic stationary phases and solid phase extraction sorbents are of great interest.
In an embodiment of the invention, a mesoporous silica is a gel product of an acid hydrolyzed, base condensed tetraalkoxysilane comprising mixture around a polyethylene glycol porogen after calcination of the porogen that has average pore diameters greater than 50 Å and a surface area in excess of 500 m2/g. The tetraalkoxysilane of the tetraalkoxysilane can be tetramethoxysilane and/or tetraethoxysilane. The mesoporous silica can have a pore volume of 1.0 cm3/g or more.
In an embodiment of the invention, the mesoporous silica is coated by the hydrolysis and condensation of a methyltrialkoxysilane and a substituted trialkoxysilane and/or a hydroxy substituted inorganic or organic polymer to form gel coated mesoporous silica particles. The methyltrialkoxysilane can be methyltrimethoxysilane or methyltriethoxysilane. The substituted trialkoxysilane is one or more selected from: an n-octyltrialkoxysilane; an n-octadecyltrialkoxysilane; a 3-cyanopropyltrialkoxy-silane; an N-trialkoxysilylpropyl-N, N,N-ammonium chloride; and a 3-mercaptopropyltrialkoxysilane, wherein the trialkoxy groups are trimethoxy and/or triethoxy groups. The inorganic or organic polymer comprises polydimethylsiloxane, polytetrahydrofuran, or polyethylene glycol.
In an embodiment of the invention, the gel coated mesoporous silica particles can be a chromatographic stationary phase or a sorbent. The chromatographic stationary phase can be a normal phase liquid chromatograph stationary phase, reverse phase liquid chromatograph stationary phase, mixed-mode liquid chromatograph stationary phase, or a gas chromatography stationary phase. The sorbent can be a solid phase sorbent.
An embodiment of the invention is directed to a method of preparing mesoporous silica particles of the mesoporous silica where one or more tetraalkoxysilanes, a sacrificial template polyethylene glycol, an organic solvent, an acid catalyst, and water are mixed until a particulate comprising fluid forms, from which the particulates are removed and a base and/or fluoride catalyst is added to the liquid to form a porogen-gel solid. The organic liquid can be or include an alcohol. The acid catalyst can be HCl, HF, or trifluoroacetic acid. The porogen-gel solid can be conditioned by the application of heat to form a conditioned porogen-gel solid that upon applying vacuum and heat forms an essentially solvent and reaction byproduct free porogen-gel solid. Upon calcining the solvent and any reaction byproducts, a mesoporous silica mass is formed. The mesoporous silica mass is crushed to form mesoporous silica particles.
An embodiment of the invention is directed to a method of preparing gel coated mesoporous silica particles where mesoporous silica particles are mixed with a liquid freed from precipitate formed from a mixture of at least one methyltrialkoxysilane and at least one substituted trialkoxysilane and/or hydroxy substituted inorganic or organic polymer, at least one solvent an acid catalyst, a solvent to form a coating on the mesoporous silica particles to form the gel coated mesoporous silica particles in a residual liquid. The gel coated mesoporous silica particles are then isolated from the residual liquid. The inorganic or organic polymer can be polydimethylsiloxane, polytetrahydrofuran, or polyethylene glycol. When the substituted trialkoxysilane includes 3-mercaptopropyltrialkoxysilane a step of oxidizing the mercapto functionality to sulfonic acid functionality can be included.
An embodiment of the invention is directed to a two steps synthesis pathway that creates robust liquid chromatographic stationary phases and solid phase extraction sorbents that are characterized by: substantially high surface areas; higher pore volumes; higher average pore widths; substantially increased pH stabilities; and high thermal stability. The synthetic method generates mesoporous silica using poly(ethylene glycol) polymers as the sacrificial template. A sol-gel reaction using acidic catalyst, for example, but not limited to HCl, for hydrolysis and subsequent polycondensation using a basic catalyst, for example, but not limited to, NH4OH, creates a sol-gel formed silica matrix in the presence of varying amount of poly(ethylene glycol), where during the gelation process a silica network homogeneously entrap poly(ethylene glycol) polymers into its core. Ultimately, upon calcination, the entrapped polymer is burned with creation of mesopores with pore size between 2 and 50 nm pore diameters and micropores with pore sizes smaller than 2 nm in diameter throughout the sol-gel silica matrix. This sponge-like mesoporous silica is coated with: reversed phase organic ligands, such as C18/C8/C4/phenyl; normal phase organic ligands, such as amino/diol/cyano; ion-exchange ligands, such as cation exchange or anion exchange ligands; mixed mode ligands, such as C18/cation-exchange or C18/anion-exchange ligands; or organic polymers with different polarities, such as poly(dimethyl siloxane), poly(ethyl glycol) (PEG), or poly(tetrahydrofuran).
This method of forming mesoporous silica and the resulting solid phases and sorbents, according to embodiments of the invention, provides numerous advantages including: chemically expanding the surface area by creating mesopores and microspores in the sol-gel silica matrix; introducing surface silanol groups that chemically bind the organic ligands/polymers but are not limited to the substrate surface but are distributed on the surface and the inside the mesopores; forming a sponge-like porous architecture of the mesoporous silica particles to allow penetration of a sol solution into its core to chemically bind relatively small organic ligands such as, C3 to C18 comprising substituents, as well as long chain inorganic or organic polymers, such as, but not limited to, poly(dimethyl siloxane), poly(tetrahydrofuran), poly(ethylene glycol) (PEG); introduction of more interaction sites per unit mass of stationary phase/solid phase extraction sorbents to the sponge-like porous architecture of sol-gel mesoporous silica matrix allowing reduction of the organic solvent usage in HPLC and SPE operation; providing an efficient pathway to creation of a large number of SPE sorbents and LC stationary phases; and resulting in sol-gel coated mesoporous materials that demonstrate extraordinary thermal stability, which can extend the range of temperatures used in LC separations past the current maximum of about 60° C. The ability to employ higher temperatures not only can modify interaction mechanisms but allows a reduction of the viscosity of the mobile phase that results in high column backpressures that can allow columns longer than 25 cm to facilitate separation of complex mixtures that are beyond the current limits imposed by the LC column length.
In embodiments of the invention, the mesoporous silica is formed from one or more tetraalkoxysilanes, which can be, but are not limited to, tetramethoxysilane and tetraethoxysilane. Optionally, tetraalkoxysilanes can be used in a polyfunctional silane mixtures with trialkoxysilanes or dialkoxysilanes, as long as the average number of alkoxy groups on the silanes exceeds three, for example 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, and 4.0 or any intermediate value. The mesoporous silica preparation is carried out using any acid catalyst, such as, but not limited to, HCl and trifluoroacetic acid (TFA) for hydrolysis in solution and any base catalyst, including, but not limited to, NH4OH, or any fluoride containing catalyst, such as, but not limited to NH4F for the condensation of the hydrolyzed and partially hydrolyzed alkoxysilanes to form a solvent and porogen filled solidified gel.
In embodiments of the invention, as shown in the reaction scheme of
By using the acid catalyzed hydrolysis subsequent base catalyzed condensation process, according to embodiments of the invention, the pore size and volume increases substantially over that where there is acid catalyzed condensation. As shown in Tables 1 and 2, the porogen does not promote a significant increase in pore size, the pore width or diameter, or pore volume with porogen content, whereas the base catalyzed condensation results in a significant increase in pore volume that is independent of porogen to tetraalkyloxysilane ratio and is 1.0 to two significant figures, with a pore size that increases significantly until the porogen to tetraalkyloxysilane ratio increases to 1.
Subsequent to calcination, as shown in
In an embodiment of the invention, the gel coated mesoporous silica comprises a stationary phase for a chromatographic separation or as a sorbent to absorb a molecule of interest, such as, but not limited to an analyte for its determination in a fluid such as water, organic solvent, air, or other gas. The gel coated mesoporous silica stationary phase resides in a column or tube through which a mobile phase liquid or gas is passed during a chromatographic process. According to an embodiment of the invention, gel coated mesoporous silica stationary phases can be used for liquid chromatography in a normal phase, reverse phase, or mixed-mode, for gas chromatography, or as a solid phase sorbent. Advantageously, the gel coated mesoporous silica stationary phase or solid phase sorbent has excellent stability to temperature, solvents, and acids and bases relative to common commercially available sorbents with equivalent functionality that are attached to a substrate other than by sol-gel coating of a mesoporous silica. As indicated in Table 3, below, for the C18 gel coating on mesoporous silica prepared as indicated in Table 6, below, relative to the commercial C18 sorbent: Supelco Discovery DSC-18 SPE.
>30%
The thermal stability allows the gel coated mesoporous silica allows the sorbent or stationary phase to be used at temperatures in excess of 100° C., or even 200° C. in many cases, where, as can be seen in
The commercial C18 sorbent and the mesoporous silica sorbents, including a sol-gel mesoporous silica C18 sorbent, have extraction efficiencies determine by exposing 50 mg of each sorbents to 10 mL aqueous solutions of the individual test compounds of Table 4 at a concentration of 1 μg/mL. The amount of extracted analytes by each of the sorbent was calculated by subtracting the chromatographic area count for each analyte in the solution before and after the extraction. As can be seen in
Tetramethyl orthosilicate, poly(ethylene glycol) and methanol were weighed/measured into a 50 mL reaction vessel and mixed on a vortex mixer to form a sol solution. Subsequently, the catalyst (0.1 M HF) was added to the sol solution and the solution was kept at room temperature until gelation occurs. The gelled silica matrix was conditioned at 50° C. for 24 h. Subsequently, the gelled silica matrix was dried in a vacuum oven at 80° C. for 24 h. The dried sol-gel particles were then calcined for 4 h at 600° C. to remove the PEG. The mesoporous silica was crushed and ground in a mortar to form fine particles.
TMOS, PEG, methanol are weighed and placed into a 50 mL reaction vessel and mixed on a vortex mixer. Subsequently, the acid catalyst was added to the sol solution and the solution was kept at 50° C. for hydrolysis. At the end of the hydrolysis, ammonium hydroxide/ammonium fluoride catalyst mixture (0.1M, 0.01 M, respectively) was added to the sol solution. The sol solution converted into gel soon after adding the base/fluoride catalyst mixture. The gelled silica matrix was conditioned at 50° C. for 24 h. Subsequently, the gelled silica matrix was dried in a vacuum oven at 80° C. for 24 h. The dried sol-gel matrix was calcined for 4 h at 600° C. to remove the PEG. The mesoporous silica was crushed and ground in a mortar to form fine particles.
A sol solution was prepared by weighing or pipetting MTMOS, n-Octadecyltrimethoxysilane (C18-TMS), dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, 3-cyanooctadecyltrimethoxysilane, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded, and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, N-trimethoxysilylpropyl-N,N,N-ammonium chloride, dichloromethane and acetone into a 50 mL, reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, 3-mercaptopropyltrimethoxysilane, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h. The dried sol-gel coated mesoporous silica was then treated with 30% H2O2 for 24 h and 0.05 M H2SO4 for 2 h for oxidation. The mercaptopropyl functional group converts to a propyl sulfonic group upon oxidation.
A sol solution was prepared by weighing or pipetting MTMOS, n-Octadecyltrimethoxysilane, N-Trimethoxysilylpropyl-N,N,N-ammonium chloride, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, n-octadecyltrimethoxysilane, 3-Mercaptopropyltrimethoxysilane, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. The sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h. The dried sol-gel coated mesoporous silica was then treated with 30% H2O2 for 24 h and 0.05 M H2SO4 for 2 h for oxidation. The mercaptopropyl functional group converts to propyl sulfonic group upon oxidation.
A sol solution was prepared by weighing or pipetting MTMOS, polydimethylsiloxane, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded, and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, polytetrahydrofuran, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded, and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
A sol solution was prepared by weighing or pipetting MTMOS, PEG, dichloromethane and acetone into a 50 mL reaction vessel. The solution was vortexed for 3 min and subsequently, trifluoroacetic acid (5% water) was added to the sol solution. The solution was centrifuged for 5 min to remove particulate matters. The supernatant was transferred to a second reaction vessel. Mesoporous silica was added to the supernatant in the second reaction vessel. The reaction vessel was kept at 50° C. in an oil bath for 6 h. Subsequently, the liquid was discarded, and the mesoporous silica coated with sol-gel tetrahydrofuran was conditioned at 50° C. overnight in an inert environment. The sol-gel coated mesoporous silica was then washed with methanol/methylene chloride (50:50 v/v) under sonication. Finally, the sol-gel coated mesoporous silica was dried in a vacuum drier for 24 h.
All patents and patent applications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.
It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.
