Patent Application
20240402159
The present disclosure describes PDI-based and UiO-66-based metal-organic frameworks (MOFs) for the detection of perfluoroalkyl and polyfluoroalkyl substances.
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a large group of laboratory-made fluorinated hydrocarbons (FHC) used to manufacture hydrophobic polymer coatings and products. Fluoropolymer coatings using PFAS are present in a variety of products, including non-stick cooking surfaces, furniture, aqueous film forming foam (AFFF) for fire extinguishing, adhesives, food packaging, clothing, and the insulation of electrical wire. The most used PFAS are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). During industrial production and widespread use of PFAS materials, it can easily seep into the soil, sludge, ground water, and air. Several PFAS, including PFOA and PFOS, do not break down in normal environmental conditions.
Due to the non-degradable nature of PFAS, dangerous and high levels can accumulate over time. Early epidemiological studies have identified links between PFOA exposure and high cholesterol, pregnancy-induced hypertension, thyroid illness, kidney and testicular cancer. The research has also disclosed that PFAS may affect the growth and learning behavior of newborns, reduce vaccine-induced immunity in children, affect the body's natural hormone production and immune system, and increase the risk of some cancers. Due to the high stability and persistence in the environment, PFAS compounds have a predisposition to bioaccumulate. The uptake of PFAS into plants and fish can occur within contaminated areas, and subsequently move into the food chain, potentially affecting wildlife and humans who consume these organisms. Thus, toxic PFAS compounds are bioaccumulated and then biomagnified up the food chain. Additionally, PFAS accumulation has been found in the blood of people and animals in various countries all over the world, which is a concern considering potential adverse health effects of PFAS. Therefore, the identification of toxic PFAS in contaminated water and removal of PFAS is becomes increasingly essential.
Currently, the standard detection techniques for PFAS primarily rely on chromatography coupled with mass spectrometry. The EPA approved official analytical techniques (“Method 537” and “Method 533”) to study different PFAS concentrations in drinking water. There is also the method of solid-phase extraction (SPE)-enabled liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the LC-MS method is accurate, it requires highly-trained laboratory personnel, complex instrumentation, and tedious sample preparation and data collection. In recent years, numerous efforts have been attempted to design a new PFAS detection platform that is not mass spectrometry dependent, is cost effective, has a fast response time, and is easy to use for onsite PFAS detection. Optical sensor materials have some intrinsic advantages, like fast response time, easy operation, cost effectiveness, naked-eye identification, and the potential to build hand-held sensor devices for onsite detection. There have been several fluorescent sensors recently developed to detect PFAS. Unfortunately, most of these reported fluorescence-based sensors currently lack sufficient selectivity, making it hard to distinguish among multiple PFAS. Considering the real field applications wherein mixture of PFASs may exist, it is essential to develop an easy-to-use, cost-effective fluorescence detection platform that can discriminatively detect against different PFAS. Selective detection of PFAS is also critical for assessing the transport of different types of PFAS in the environment and monitoring the effectiveness of abatement processes onsite.
Fluorescent metal-organic frameworks (MOFs) have evolved as a next-generation functional material because of their ultra-high porosity, large surface area, structural diversity and tunability. Based on these unique properties, a large number of MOF-based sensors have been developed in recent years for a broad range of applications in the field of fluorescence sensing. These applications include detection of volatile organic compounds, explosives, biomolecules, heavy metals, and many more. Very recently, three known zirconium porphyrinic MOFs (PCNs, i.e., PCN-222, PCN-223, and PCN-224) have been explored for PFAS detection using sensor arrays. The method used by others relies on a fluorescence “turn-off” response to detect PFAS. However, this approach can result in false “turn-off” signals due to unwanted contamination. In contrast, using fluorescent “turn-on” probes that switch their fluorescence from “off” (fluorescence quenching) to “on” (or fluorescence activating) not only amplifies the target signals but also reduces the background signal, resulting in a lower detection limit and improved sensitivity.
Therefore, what is needed are novel fluorescent MOF-based fluorescence activating probes and corresponding methods for the selective detection and removal of PFAS with said MOF-based fluorescence activating probes.
One embodiment described herein is a composition comprising at least one metal-organic framework (MOF), or salt thereof, the metal-organic framework comprising: a plurality of metal-containing secondary building units (SBU) linked together by one or more bridging ligands, wherein said bridging ligands, or salts thereof, have a formula (I):
In another aspect, R1, at each occurrence, is halo. In another aspect, R1, at each occurrence, is chloro. In another aspect, R2, at each occurrence, is C1-8alkyl. In another aspect, R2, at each occurrence is C1alkyl. In another aspect, the bridging ligands, or salts thereof, are selected from:
In another aspect, the secondary building units comprise one or more metal atoms and one or more carboxylates. In another aspect, the composition further comprises one or more modulators. In another aspect, the modulators are trifluoroacetic acid. In another aspect, the metal atoms comprise zirconium(IV) or hafnium(IV).
Another embodiment described herein is a method for detecting or removing perfluoroalkyl or polyfluoroalkyl substances in a sample, the method comprising: contacting the sample with a composition comprising at least one metal-organic framework (MOF), or salt thereof, having a plurality of metal-containing secondary building units (SBU) linked together by one or more bridging ligands, wherein said bridging ligands, or salts thereof, have a formula (I):
In another aspect, R1, at each occurrence, is halo. In another aspect, R1, at each occurrence, is chloro. In another aspect, R2, at each occurrence, is C1-8alkyl. In another aspect, R2, at each occurrence, is C1alkyl. In another aspect, R2, at each occurrence, is hydrogen. In another aspect, the bridging ligands, or salts thereof, are selected from:
In another aspect, the secondary building units comprise one or more metal atoms or one or more carboxylates. In another aspect, the composition further comprises one or more modulators. In another aspect, the modulators are trifluoroacetic acid. In another aspect, the metal atoms comprise zirconium(IV) or hafnium(IV). In another aspect, the one or more perfluoroalkyl or polyfluoroalkyl substances is perfluooctanoic acid (PFOA). In another aspect, the composition is noncovalently adhered or covalently attached to a surface. In another aspect, the surface comprises cellulose, silica, a polymer, a copolymer, a resin, a filter, or a combination thereof. In another aspect, the composition is dissolved in a solvent. In another aspect, the change is an increase in fluorescence intensity. In another aspect, the change in fluorescence intensity indicate removal of the perfluoroalkyl or polyfluoroalkyl substances from the sample. In another aspect, the composition has a limit of detection of about 1-50 ppb.
Another embodiment described herein is a method for detecting or removing perfluoroalkyl or polyfluoroalkyl substances in a sample, the method comprising: contacting the sample with a composition comprising at least one metal-organic framework (MOF), or salt thereof, having a plurality of metal-containing secondary building units (SBU) linked together by one or more bridging ligands, wherein said bridging ligands, or salts thereof, have a formula (II):
In another aspect, the bridging ligands, or salts thereof, are selected from:
In another aspect, the secondary building units comprise one or more metal atoms and one or more carboxylates. In another aspect, the metal atoms comprise zirconium(IV) or hafnium(IV). In another aspect, the one or more perfluoroalkyl or polyfluoroalkyl substances is perfluooctanoic acid (PFOA). In another aspect, the composition is noncovalently adhered or covalently attached to a surface. In another aspect, the surface comprises cellulose, silica, a polymer, a copolymer, a resin, a filter, or a combination thereof. In another aspect, the composition is dissolved in a solvent. In another aspect, the change is an increase in fluorescence intensity. In another aspect, the change in fluorescence intensity indicates removal of perfluoralkyl or polyfluoroalkyl substances from the sample. In another aspect, the composition has a limit of detection of about 1-50 ppb.
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various way.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present invention. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.
The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.
The modifier “about” used in connection with a quantity is inclusive of the stated value and has the meaning dictated by the context (for example, it includes at least the degree of error associated with the measurement of the particular quantity). The modifier “about” should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression “from about 2 to about 4” also discloses the range “from 2 to 4.” The term “about” may refer to plus or minus 10% of the indicated number. For example, “about 10%” may indicate a range of 9% to 11%, and “about 1” may mean from 0.9-1.1. Other meanings of “about” may be apparent from the context, such as rounding off, so, for example “about 1” may also mean from 0.5 to 1.4.
As used herein “or” can mean the conjunctive or disjunctive. For example, two actions separated by an “or” can be performed either simultaneously, sequentially, or separately.
It will be understood that when a feature, such as a layer, region or substrate, is referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when an element is referred to as being “directly on” another feature or element, there are no intervening elements present.
As used herein, the term “complex” and “composition” may be used interchangeably.
As used herein, the term “coordinated” or “coordination” describes the interaction between a metal atom and a ligand, including but not limited to atoms, ions, or molecules. As used herein, coordination and “link” or “linking” may be used interchangeably.
As used herein, the term “non-covalently adhered” describes interactions between atom, ions, and molecules that do not involve the sharing of electrons.
As used herein, the term “covalently attached” describes interactions between atoms, ions, and molecule that do involve the sharing of electrons.
As used herein, the term “bind” or “bound” may refer to either or both covalent and non-covalent interactions.
As used herein, the term “metal organic framework” or “MOF”, refers to a complex comprising one or more secondary building units and one or more bridging ligands. In some embodiments, the complex further comprises one or more modulators. In one aspect, the modulators are trifluoroacetic acid. In another aspect, the modulators are weakly bound to the secondary building units, the bridging ligands, or a combination of the bridging ligand and the secondary building units. In another aspect, the modulators maintain the coordination between the secondary building units and bridging ligands together in the absence of an analyte. In another aspect, the presence of an analyte displaces trifluoroacetic acid and the analyte binds to the location where trifluoroacetic acid previously existed.
As used herein, “secondary building units” also referred to as SBU, refers to the component of the MOF comprising one or more metal atoms and one or more complexing agent. The “base” of the secondary building units, as described herein, is the one or more metal atoms. In some embodiments, the metal atoms are linked by bridging oxygen or hydroxyl groups. In some embodiments, the metal atoms are further coordinated to at least one bridging ligand. In some embodiments, the one or more complexing agent is a sulfate or carboxylate salt. In some embodiments, the carboxylate salt is formate, benzoate, or acetate.
MOFs generally are known in the art and encompass structures in which a metal base is coordinated to an at least bidentate bridging ligands to form a coordination network. Such structures may be one-dimensional, two-dimensional, or three-dimensional. The MOFs of the present disclosure are porous, and may include pores that occur in the pores between the metal ions and the coordination network of the one or more bridging ligands. The pores may be micropores, 2 nm or less in diameter, or mesopores, 2-50 nm in diameter.
A number of methods for producing MOFs are known in the art. The most common technique involves the reaction of a metal salt with the desired bridging ligand in a suitable solvent, typically an organic solvent such as Dimethylformamide (DMF). High pressures and temperatures are generally required to facilitate the reaction. Typical processes are disclosed in, for example, WO 2009/133366, WO 2007/023134, WO2007/090809 and WO 2007/118841.
In some embodiments, the one or more metal atoms may be zirconium, hafnium, titanium, or cerium. In some embodiments, the one or more atom metals ions may be present in an amount of at most 50 wt. %, preferably at most 25 wt. %, more preferably at most 10 wt. %, for example at most 5 wt. %, relative to the total amount of metal ions.
The bridging ligands described herein are capable of being coordinated to at least two metal atoms through at least one organic moiety. As described herein an “organic moiety” means a carbon-based group that includes at least one C—H bond and which may optionally include one or more heteroatoms such as N, O, S, B, P, Si. Typically, the organic moiety comprises from 1 to 75 carbon atoms. In some embodiments, the bridging ligand is the ligand itself or a salt thereof.
In some embodiments, the bridging ligand is at least bidentate. As described herein “bidentate” refers to two functional groups capable of basic coordination with a metal atom. The bridging ligand compound may also be tridentate (i.e., containing three functional groups) or tetradentate (i.e., containing four functional groups). In some embodiments, the bridging ligand coordination involves the supplying of electron from the bridging ligand to the base.
In some embodiments, the bridging ligand may be water soluble. Water solubility, as described herein, refers to solubility in water which is high enough to ensure that a homogeneous solution is formed in water. The solubility of the organic linker compound in water may be at least 1 g/L, such as at least 2 g/L, or at least 5 g/L at Room Temperature and Pressure (RTP).
In some embodiments, the bridging ligand comprises an aromatic moiety. The aromatic moiety may have one or more aromatic rings, for example two-, three-, four-, five-, six-, seven-, eight-, nine-, or ten rings, which can be present separately from each other and/or at least two rings may be present in a fused form. In some embodiment, each ring of the moiety may independently include at least one heteroatom, such as N, O, S, B, P, Si, preferably N, O and/or S. In some embodiments, the bridging ligand comprises a perylene diimide. In some embodiments, the perylene diimide is substituted with other functional groups.
Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference.
The term “alkoxy,” as used herein, refers to a group —O-alkyl. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert-butoxy.
The term “alkyl,” as used herein, means a straight or branched, saturated hydrocarbon chain. The term “lower alkyl” or “C1-6alkyl” means a straight or branched chain hydrocarbon containing from 1 to 6 carbon atoms. The term “C1-4alkyl” means a straight or branched chain hydrocarbon containing from 1 to 4 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.
The term “alkenyl,” as used herein, means a straight or branched, hydrocarbon chain containing at least one carbon-carbon double bond.
The term “alkoxyalkyl,” as used herein, refers to an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein.
The term “alkylamino,” as used herein, means at least one alkyl group, as defined herein, is appended to the parent molecular moiety through an amino group, as defined herein.
The term “amide,” as used herein, means —C(O)NR— or —NRC(O)—, wherein R may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl.
The term “aminoalkyl” as used herein, means at least one amino group, as defined herein, is appended to the parent molecular moiety through an alkylene group, as defined herein.
The term “amino,” as used herein, means —NRxRy, wherein Rx and Ry may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl. In the case of an aminoalkyl group or any other moiety where amino appends together two other moieties, amino may be —NRx-, wherein Rx may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl.
The term “aryl,” as used herein, refers to a phenyl or a phenyl appended to the parent molecular moiety and fused to a cycloalkane group (e.g., the aryl may be indan-4-yl), fused to a 6-membered arene group (i.e., the aryl is naphthyl), or fused to a non-aromatic heterocycle (e.g., the aryl may be benzo[d][1,3]dioxol-5-yl). The term “phenyl” is used when referring to a substituent and the term 6-membered arene is used when referring to a fused ring. The 6-membered arene is monocyclic (e.g., benzene or benzo). The aryl may be monocyclic (phenyl) or bicyclic (e.g., a 9- to 12-membered fused bicyclic system).
The term “cyanoalkyl,” as used herein, means at least one —CN group, is appended to the parent molecular moiety through an alkylene group, as defined herein.
The term “cycloalkoxy,” as used herein, refers to a cycloalkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom.
The term “cycloalkyl” or “cycloalkane,” as used herein, refers to a saturated ring system containing all carbon atoms as ring members and zero double bonds. The term “cycloalkyl” is used herein to refer to a cycloalkane when present as a substituent. A cycloalkyl may be a monocyclic cycloalkyl (e.g., cyclopropyl), a fused bicyclic cycloalkyl (e.g., decahydronaphthalenyl), or a bridged cycloalkyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptanyl). Representative examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, adamantyl, and bicyclo[1.1.1]pentanyl.
The term “cycloalkenyl” or “cycloalkene,” as used herein, means a non-aromatic monocyclic or multicyclic ring system containing all carbon atoms as ring members and at least one carbon-carbon double bond and preferably having from 5-10 carbon atoms per ring. The term “cycloalkenyl” is used herein to refer to a cycloalkene when present as a substituent. A cycloalkenyl may be a monocyclic cycloalkenyl (e.g., cyclopentenyl), a fused bicyclic cycloalkenyl (e.g., octahydronaphthalenyl), or a bridged cycloalkenyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptenyl). Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl.
The term “carbocyclyl” means a “cycloalkyl” or a “cycloalkenyl.” The term “carbocycle” means a “cycloalkane” or a “cycloalkene.” The term “carbocyclyl” refers to a “carbocycle” when present as a substituent.
The terms cycloalkylene and heterocyclylene refer to divalent groups derived from the base ring, i.e., cycloalkane, heterocycle. For illustration, an example cycloalkylene may be cyclohexene or
and a heterocyclylene may be
Cycloalkylene and heterocyclylene include a geminal divalent groups such as 1,1-C3-6cycloalkylene. A further example is 1,1-cyclopropylene.
The term “halogen” or “halo,” as used herein, means C1, Br, I, or F.
The term “haloalkyl,” as used herein, means an alkyl group, as defined herein, in which one, two, three, four, five, six, seven or eight hydrogen atoms are replaced by a halogen.
The term “haloalkoxy,” as used herein, means at least one haloalkyl group, as defined herein, is appended to the parent molecular moiety through an oxygen atom.
The term “halocycloalkyl,” as used herein, means a cycloalkyl group, as defined herein, in which one or more hydrogen atoms are replaced by a halogen.
The term “heteroalkyl,” as used herein, means an alkyl group, as defined herein, in which one or more of the carbon atoms has been replaced by a heteroatom selected from S, O, P and N. Representative examples of heteroalkyls include, but are not limited to, alkyl ethers, secondary and tertiary alkyl amines, amides, and alkyl sulfides.
The term “heteroaryl,” as used herein, refers to an aromatic monocyclic heteroatom-containing ring (monocyclic heteroaryl) or a bicyclic ring system containing at least one monocyclic heteroaromatic ring (bicyclic heteroaryl). The term “heteroaryl” is used herein to refer to a heteroarene when present as a substituent. The monocyclic heteroaryl are five or six membered rings containing at least one heteroatom independently selected from the group consisting of N, O and S (e.g., 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N). The five membered aromatic monocyclic rings have two double bonds, and the six membered aromatic monocyclic rings have three double bonds. The bicyclic heteroaryl is an 8- to 12-membered ring system and includes a fused bicyclic heteroaromatic ring system (i.e., 1071 electron system) such as a monocyclic heteroaryl ring fused to a 6-membered arene (e.g., quinolin-4-yl, indol-1-yl), a monocyclic heteroaryl ring fused to a monocyclic heteroarene (e.g., naphthyridinyl), and a phenyl fused to a monocyclic heteroarene (e.g., quinolin-5-yl, indol-4-yl). A bicyclic heteroaryl/heteroarene group includes a 9-membered fused bicyclic heteroaromatic ring system having four double bonds and at least one heteroatom contributing a lone electron pair to a fully aromatic 107L electron system, such as ring systems with a nitrogen atom at the ring junction (e.g., imidazopyridine) or a benzoxadiazolyl. A bicyclic heteroaryl also includes a fused bicyclic ring system composed of one heteroaromatic ring and one non-aromatic ring such as a monocyclic heteroaryl ring fused to a monocyclic carbocyclic ring (e.g., 6,7-dihydro-5H-cyclopenta[b]pyridinyl), or a monocyclic heteroaryl ring fused to a monocyclic heterocycle (e.g., 2,3-dihydrofuro[3,2-b]pyridinyl). The bicyclic heteroaryl is attached to the parent molecular moiety at an aromatic ring atom. Other representative examples of heteroaryl include, but are not limited to, indolyl (e.g., indol-1-yl, indol-2-yl, indol-4-yl), pyridinyl (including pyridin-2-yl, pyridin-3-yl, pyridin-4-yl), pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl (e.g., pyrazol-4-yl), pyrrolyl, benzopyrazolyl, 1,2,3-triazolyl (e.g., triazol-4-yl), 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, imidazolyl, thiazolyl (e.g., thiazol-4-yl), isothiazolyl, thienyl, benzimidazolyl (e.g., benzimidazol-5-yl), benzothiazolyl, benzoxazolyl, benzoxadiazolyl, benzothienyl, benzofuranyl, isobenzofuranyl, furanyl, oxazolyl, isoxazolyl, purinyl, isoindolyl, quinoxalinyl, indazolyl (e.g., indazol-4-yl, indazol-5-yl), quinazolinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, isoquinolinyl, quinolinyl, imidazo[1,2-a]pyridinyl (e.g., imidazo[1,2-a]pyridin-6-yl), naphthyridinyl, pyridoimidazolyl, thiazolo[5,4-b]pyridin-2-yl, and thiazolo[5,4-d]pyrimidin-2-yl.
The term “heterocycle” or “heterocyclic,” as used herein, means a monocyclic heterocycle, a bicyclic heterocycle, or a tricyclic heterocycle. The term “heterocyclyl” is used herein to refer to a heterocycle when present as a substituent. The monocyclic heterocycle is a three-, four-, five-, six-, seven-, or eight-membered ring containing at least one heteroatom independently selected from the group consisting of O, N, and S. The three- or four-membered ring contains zero or one double bond, and one heteroatom selected from the group consisting of O, N, and S. The five-membered ring contains zero or one double bond and one, two or three heteroatoms selected from the group consisting of O, N and S. The six-membered ring contains zero, one or two double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. The seven- and eight-membered rings contains zero, one, two, or three double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. Representative examples of monocyclic heterocyclyls include, but are not limited to, azetidinyl, azepanyl, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, 2-oxo-3-piperidinyl, 2-oxoazepan-3-yl, oxadiazolinyl, oxadiazolidinyl, oxazolinyl, oxazolidinyl, oxetanyl, oxepanyl, oxocanyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, 1,2-thiazinanyl, 1,3-thiazinanyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl (thiomorpholine sulfone), thiopyranyl, and trithianyl. The bicyclic heterocycle is a monocyclic heterocycle fused to a 6-membered arene, or a monocyclic heterocycle fused to a monocyclic cycloalkane, or a monocyclic heterocycle fused to a monocyclic cycloalkene, or a monocyclic heterocycle fused to a monocyclic heterocycle, or a monocyclic heterocycle fused to a monocyclic heteroarene, or a spiro heterocycle group, or a bridged monocyclic heterocycle ring system in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. The bicyclic heterocyclyl is attached to the parent molecular moiety at a non-aromatic ring atom (e.g., indolin-1-yl). Representative examples of bicyclic heterocyclyls include, but are not limited to, chroman-4-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzothien-2-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, azabicyclo[2.2.1]heptyl (including 2-azabicyclo[2.2.1]hept-2-yl), azabicyclo[3.1.0]hexanyl (including 3-azabicyclo[3.1.0]hexan-3-yl), 2,3-dihydro-1H-indol-1-yl, isoindolin-2-yl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolopyridinyl, tetrahydroisoquinolinyl, 7-oxabicyclo[2.2.1]heptanyl, hexahydro-2H-cyclopenta[b]furanyl, 2-oxaspiro[3.3]heptanyl, 3-oxaspiro[5.5]undecanyl, 6-oxaspiro[2.5]octan-1-yl, and 3-oxabicyclo[3.1.0]hexan-6-yl. Tricyclic heterocycles are exemplified by a bicyclic heterocycle fused to a 6-membered arene, or a bicyclic heterocycle fused to a monocyclic cycloalkane, or a bicyclic heterocycle fused to a monocyclic cycloalkene, or a bicyclic heterocycle fused to a monocyclic heterocycle, or a bicyclic heterocycle in which two non-adjacent atoms of the bicyclic ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. Examples of tricyclic heterocycles include, but are not limited to, octahydro-2,5-epoxypentalene, hexahydro-2H-2,5-methanocyclopenta[b]furan, hexahydro-1H-1,4-methanocyclopenta[c]furan, aza-adamantane (1-azatricyclo[3.3.1.13,7]decane), and oxa-adamantane (2-oxatricyclo[3.3.1.13,7]decane). The monocyclic, bicyclic, and tricyclic heterocyclyls are connected to the parent molecular moiety at a non-aromatic ring atom.
The term “hydroxyl” or “hydroxy,” as used herein, means an —OH group.
The term “hydroxyalkyl,” as used herein, means at least one —OH group, is appended to the parent molecular moiety through an alkylene group, as defined herein.
Terms such as “alkyl,” “cycloalkyl,” “alkylene,” etc. may be preceded by a designation indicating the number of atoms present in the group in a particular instance (e.g., “C1-4alkyl,” “C3-6cycloalkyl,” “C1-4alkylene”). These designations are used as generally understood by those skilled in the art. For example, the representation “C” followed by a subscripted number indicates the number of carbon atoms present in the group that follows. Thus, “C3alkyl” is an alkyl group with three carbon atoms (i.e., n-propyl, isopropyl). Where a range is given, as in “C1-4,” the members of the group that follows may have any number of carbon atoms falling within the recited range. A “C1-4alkyl,” for example, is an alkyl group having from 1 to 4 carbon atoms, however arranged (i.e., straight chain or branched).
The term “substituted” refers to a group that may be further substituted with one or more non-hydrogen substituent groups. Substituent groups include, but are not limited to, halogen, ═O (oxo), ═S (thioxo), cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinyl, —COOH, ketone, amide, carbamate, and acyl.
The bridging ligands described herein are set forth in the following numbered embodiments. The first embodiment is denoted E1, another embodiment is denoted E2 and so forth.
E1. A bridging ligand of formula (I), or salt thereof:
E2. The bridging ligand of E1, or salt thereof, wherein G1, at each occurrence, is phenyl.
E3. The bridging ligand of E1 or E2, or salt thereof, have a formula (Ia):
E4. The bridging ligand of any one of E1-3, or salt thereof, wherein R1, at each occurrence, is halo.
E5. The bridging ligand of any one of E1-4, or salt thereof, wherein R1, at each occurrence, is chloro.
E6. The bridging ligand of any one of E1-5, or salt thereof, wherein R2, at each occurrence, is C1-8alkyl.
E7. The bridging ligand of any one of E1-6, or salt thereof, wherein R2, at each occurrence, is C1alkyl.
E8. The bridging ligand of any one of E1-7, or salt thereof, wherein every R2 is not hydrogen.
E9. The bridging ligand of any one of E1-8, or salt thereof, wherein the bridging ligand, or salts thereof, is selected from:
E10. A bridging ligand of formula (II), or salt thereof:
E11. The bridging ligand of E10, wherein the bridging ligands have a formula (IIa):
E12. The bridging ligand of E10 or E11, wherein the bridging ligand, or salt thereof, is selected from:
In some embodiments, the MOF containing the bridging ligand described herein is selective or non-selective for one or more perfluoroalkyl or polyfluoroalkyl substances. In some embodiments, the limit of detection is about 1 to about 50 parts per billion (ppb). In one aspect, the limit of detection is about 1 ppb, 2 ppb, 3 ppb, 4 ppb, 5 ppb, 6 ppb, 7 ppb, 8 ppb, 9 ppb, 10 ppb, 15 ppb, 20 ppb, 25 ppb, 30 ppb, 35 ppb, 40 ppb, 45 ppb, 50 ppb, or greater. In another aspect, the limit of detection is about 1-10 ppb, 1-15 ppb, 1-20 ppb, 1-25 ppb, 1-30 ppb, 1-35 ppb, 1-40 ppb, 1-45 ppb, 1-50 ppb, 2-10 ppb, 2-15 ppb, 2-20 ppb, 2-25 ppb, 2-30 ppb, 2-35 ppb, 2-40 ppb, 2-45 ppb, 2-50 ppb, 5-10 ppb, 5-15 ppb, 5-20 ppb, 5-25 ppb, 5-30 ppb, 5-35 ppb, 5-40 ppb, 5-45 ppb, 5-50 ppb, 10-20 ppb, 10-25 ppb, 10-30 ppb, 10-35 ppb, 10-40 ppb, 10-45 ppb, 10-50 ppb, including all endpoints, integers and subranges within the disclosed ranges.
The MOFs and bridging ligands described herein may exist as salts. In some embodiments the compounds may exist as pharmaceutically acceptable salts. The term “pharmaceutically acceptable salt” refers to salts or zwitterions of the compounds which are water or oil-soluble or dispersible, suitable for treatment of disorders without undue toxicity, irritation, and allergic response, commensurate with a reasonable benefit/risk ratio and effective for their intended use. The salts may be prepared during the final isolation and purification of the compounds or separately by reacting an amino group of the compounds with a suitable acid. For example, a compound may be dissolved in a suitable solvent, such as but not limited to methanol and water and treated with at least one equivalent of an acid, like hydrochloric acid. The resulting salt may precipitate out and be isolated by filtration and dried under reduced pressure. Alternatively, the solvent and excess acid may be removed under reduced pressure to provide a salt. Representative salts include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, formate, isethionate, fumarate, lactate, maleate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, oxalate, maleate, pivalate, propionate, succinate, tartrate, thrichloroacetate, trifluoroacetate, glutamate, para-toluenesulfonate, undecanoate, hydrochloric, hydrobromic, sulfuric, phosphoric and the like. The amino groups of the compounds may also be quaternized with alkyl chlorides, bromides and iodides such as methyl, ethyl, propyl, isopropyl, butyl, lauryl, myristyl, stearyl and the like.
Basic addition salts may be prepared during the final isolation and purification of the disclosed compounds by reaction of a carboxyl group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation such as lithium, sodium, potassium, calcium, magnesium, or aluminum, or an organic primary, secondary, or tertiary amine. Quaternary amine salts can be prepared, such as those derived from methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine and N,N′-dibenzylethylenediamine, ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine, and the like.
In some embodiments, the organic ligand may possess fluorescence. In separate embodiments, the organic ligand may exhibit an increase in fluorescence in the presence of an analyte. As used herein, “fluorescence” is a cyclical process where a luminescence is generated by certain molecules in which the molecular absorption of a photon triggers the emission of another photon with a longer wavelength. Certain molecules are capable of being excited, via absorption of light energy, to a higher energy state, also called an excited state. The energy of this short-lived excited state decays (or decreases) resulting in the emission of light energy. The emission of light via this process is “fluorescence.” Molecules that emit light in this manner are said to “fluoresce” and are generally referred to as “fluorophores” or “fluorescent dyes.”.
A “fluorophore” or “fluorescent dye,” as used herein, is a molecule that is capable of fluorescing. In its ground state, the fluorophore molecule is in a relatively low-energy, stable configuration, and it does not fluoresce. When light from an external source of one or more particular wavelengths contacts a fluorophore, the fluorophore can absorb the light energy. If the fluorophore absorbs sufficient energy, the fluorophore is excited to an excited state (high energy); this process is known as excitation. There may be multiple excited states or high energy levels that a fluorophore can attain, depending on the wavelength and energy of the external light source. Since a fluorophore is unstable at high-energy configurations, it eventually decays to the lowest-energy excited state, which is semi-stable. The excited lifetime (the length of time that a fluorophore is an excited state) is very short; the fluorophore the decays from the semi-stable excited state back to the ground state, and at least a portion of the excess energy released by this decay may be emitted as light. The emitted light is of a lower energy, and a longer wavelength, than the absorbed light, and thus the color of the light that is emitted is different from the color of the light that has been absorbed. upon reaching the ground state, a fluorophore can again absorb light energy to enter an excited state.
A fluorophore or fluorescent dye absorbs light over a range of wavelengths and every dye has a characteristic range of excitation wavelengths. This range of excitation wavelengths is referred to as the fluorescence “excitation spectrum” and reflects the range of possible excited states that the dye can achieve. Certain wavelengths within this range are more effective for excitation than other wavelengths. A fluorophore is excited most efficiently by light of a particular wavelength. This wavelength is the excitation maximum for the fluorophore. As used herein “excitation maximum” refers to the specific wavelength for each fluorescent dye that most effectively induces fluorescence. Less efficient excitation can occur at wavelengths near the excitation maximum; however, the intensity of the emitted fluorescence is reduced. Although illumination at the excitation maximum of the fluorophore produces the greatest fluorescence output, illumination at lower or higher wavelengths affects only the intensity of the emitted light; the range and overall shape of the emission profile are unchanged.
As used herein, “excitation” refers to the process where a photon of energy supplied by an external source, such as a laser or a lamp, is absorbed by the fluorophore creating an excited electronic singlet state (S1′) from the S0 ground state. The excited state exists for a finite time during which the fluorophore undergoes conformational changes and is also subject to a multitude of possible interactions with its molecular environment. These processes have two important consequences. One of these consequences is that the energy of S1′ is partially dissipated, yielding a relaxed singlet excited state (S1) from which fluorescence emission originates. Molecules in an excited state (S1′) can relax by various competing pathways, They can undergo ‘non-radiative relaxation’ in which the excitation energy is dissipated as heat (vibrations) to the solvent. Excited organic molecules can also relax via conversion to a triplet state which may subsequently relax via phosphorescence or by a secondary non-radiative relaxation step. The term “relax” as used herein refers to the energy loss of an excited molecule, Not all the molecules initially excited by absorption return to the ground state (S0) by fluorescence emission. Relaxation of an S1′ state can also occur through interaction with a second molecule through fluorescence quenching. Other processes, such as, but not limited to, collisional quenching or fluorescent resonance energy transfer (FRET), may also depopulate S1.
FRET is now widely known in the art. FRET is a radiationless process in which energy is transferred from an excited donor molecule to an acceptor molecule. Radiationless energy transfer is the quantum-mechanical process by which the energy of the excited state of one fluorophore is transferred without actual photon emission to a second fluorophore or molecule. The quantum physical principles are reviewed in Jovin and Jovin, 1989, Cell Structure and Function by Microspectrofluorometry. eds. E, Kohen and J. C. G Hirschberg, Academic Press incorporated herein by reference for the teachings. Briefly, a fluorophore absorbs light energy at a characteristic wavelength. The first fluorophore is generally termed the donor (“D”) and my have an excited state of higher energy than that of the second fluorophore, termed the acceptor (“A”).
An essential feature of FRET is that the emission spectrum of the donor overlap with the excitation spectrum of the acceptor, and that the donor and acceptor be sufficiently close. In addition, the distance between “D” and “A” must be sufficiently small to allow the radiationless transfer of energy between the fluorophores. Because the rate of energy transfer is inversely proportional to the sixth power of the distance between the donor and acceptor, the energy transfer efficiency is extremely sensitive to distance changes. Energy transfer is said to occur with detectable efficiency in the 1-10 nm distance range but is typically 4-6 nm for optimal results. The distance range over which radiationless energy transfer is effective depends on many other factors as well, including the fluorescence quantum efficiency of the donor, the extinction coefficient of the acceptor, the degree of overlap of their respective spectra, the refractive index of the medium, and the relative orientation of the transition moments of the two fluorophores.
As used herein, the term “quencher” means a substance, which reduces or quenches the emission of fluorescence from a fluorophore. As used herein, “fluorescence quenching” may be achieved by any mechanism, typically by FRET between a fluorophore and a non-fluorescent quenching moiety or by collisional (i.e., contact) quenching.
Fluorophore molecules, when excited, emit over a range of wavelengths. This range of wavelengths is referred to as the fluorescence “emission spectrum.” There is a spectrum of energy changes associated with these emission events. The emission maximum is the wavelength where the population of molecules fluoresces most intensely. The emission maximum for a given fluorophore is always at a longer wavelength (lower energy) than the excitation maximum. This difference between the excitation and emission maxima is called the Stokes shift. The magnitude of the Stokes shift is determined by the electronic structure of the fluorophore and is characteristic of the fluorophore molecule. The Stokes shift occurs because some of the energy of the excited fluorophore is lost through molecular vibrations that occur during the brief lifetime of the molecule's excited state, which is dissipated as heat to surrounding solvent molecules as they collide with the excited fluorophore, Remaining energy that is emitted as light fluorescence is thus less than the amount of energy required for excitation.
Fluorescence requires a source of excitation energy, There are many light source options for fluorescence, Selecting the appropriate light source, and filters for both excitation and emission, can increase the sensitivity of signal detection.
Several types of light sources are used to excite fluorescent dyes. The most common sources used are broadband sources, such as, for example, mercury-arc and tungsten-halogen lamps. These lamps produce white light that has peaks of varying intensity across the spectrum. When using broadband white light sources, it is necessary to filter the desired wavelengths needed for excitation; this is most often done using optical filters. Optical filters selectively allow light of certain wavelengths to pass while blocking out undesirable wavelengths. A bandpass excitation filter transmits a narrow range of wavelengths and may be used for selective excitation.
Laser excitation sources provide wavelength peaks that are well-defined, selective, and of high intensity allowing more selective illumination of the sample. The best performance is achieved when the dye's peak excitation wavelength is close to the wavelength of the laser. Several lasers commonly used include, for example, the compact violet 405 nm laser, 488 nm blue-green argon-ion laser, 543 nm helium-neon green laser, and 633 nm helium-neon red laser, Mixed-gas lasers such as, for example, the krypton-argon laser, can output multiple laser lines which may require optical filters to achieve selective excitation. High-output light-emitting diodes (LEDs) provide selective wavelengths, low cost and energy consumption, and long lifetime. Single-color LEDs are ideal for low-cost instrumentation where they can be combined with simple long-pass filters that block the LED excitation and allows the transmission of the dye signal. However, the range of wavelengths emitted from each LED is still relatively broad and may also require the use of a filter to narrow the bandwidth.
Filters are important for selecting excitation wavelengths and for isolating the fluorescence emission emanating from the dye of interest, Stray light arising from sources other than the emitting fluorophores (for example, from the excitation source) interferes with the detection of the fluorescence emission. Stray light therefore must be contained to ensure only the fluorescence of the sample registers with the instrument's light-sensitive detectors. When a single fluorophore is used, a long pass emission filter which selectively blocks out the excitation light to reduce background noise nay be used to maximize the signal collected. If multiple fluorophores are used in the sample, a band pass emission filter can be used to isolate the emission from each dye.
In some embodiments, the MOF may be covalently attached or non-covalently adhered to a surface. In some embodiments, the surface is a “solid phase extraction membranes” or “SPE membranes.” As used herein, “surface” and “solid-phase extraction membrane” may be used interchangeably. As used herein a surface may comprise a polymer, a copolymer, a resin, a filter, silica, or a combination thereof. In some embodiments, the polymer may be selected from a polytetrafluoroethylene, a polyvinylidene difluoride, a nitrocellulose, a cellulose acetate, a polyacrylonitrile, a polyimide, a polycarbonate, and a polypropylene, among other suitable polymers. In some embodiments, the surface may comprises a polymer forming a porous polymeric aggregate or polymeric fibers with microparticles and/or nanoparticles embedded in the polymer. A “microparticle” or “nanoparticle” used herein refers to a plurality of particles that either adsorb or absorb liquids. In some embodiments the microparticle or nanoparticle may be formed of a silica, an activated carbon, a cation exchange resin, an anion exchange resin, a chelating agent, a polystyrenedivinylbenzene, or a reverse phase sulfonated polystyrenedivinylbenzene, among other suitable materials. In some embodiments, the microparticles or nanoparticles are C8 or C18 bonded silica. In some embodiments, the average particle size of the solid phase extraction membrane may be from about 0.5 μm to about 20 μm. In some embodiments, the average particle size may be from about 5 μm to about 15 μm. In some embodiments, the average particle size may be from 10 μm to about 15 μm. In some embodiments, the pore size of the SPE membrane is about 0.1 μm to about 10 μm. In some embodiments, the SPE membrane may be housed in a disk or other compatible apparatus. When the SPE membrane is housed in a disk, the diameter of the disk may range from about 5 mm to about 100 mm. In some embodiments, the SPE membrane may exist separate from a disk to allow for fluorescence imaging.
In some embodiments, an organic linker or organic ligand, as described herein, may be covalently or non-covalently adhered on a surface or a solid-phase extraction (“SPE”) membrane. In some embodiments, the organic ligand may be covalently coupled to a surface and resulting fluorescence is detected directly on the surface. For example, the organic ligand may be covalently attached to the surface by a linker, including any linker to those skilled in the art or hereinafter developed. The linker may be formed by reaction of one or more functional groups on the surface and one or more functional groups on the organic linker or ligand. Exemplary linking chemistry may include but is not limited to modifying the silica gel surface with amino-alkyl-trimethoxysilane, or amino-alkyl-triethoxysilane, to form an activated silica comprising an amine. Subsequently tethering the organic ligand via reaction with the amine moiety of the activated silica. The —OH, —COOH, or —NH2 groups on the surface of polymer or silica can be strongly bound to with the metal salt used for MOF synthesis (Zr4+) through coordination. For example, the polymer or silica may be treated with the metal salt alone to form a metal ion coating on the surface as a nucleation site for MOF. In the next step, both the metal salt and ligand are added and grow MOFs on the surface of the polymer or silica support by following standard solvothermal reaction conditions used for MOF synthesis. Since the metal ion is already attached to the surface of the support, the MOF starts growing on the surface. In some embodiments, the organic linker or ligand may be non-covalently adhered to the surface, such as via intramolecular interactions including, but not limited to, electrostatic interactions, 7-effects interactions, hydrogen bonding, van der Waals forces, and/or hydrophobic interactions. In some embodiments, either together or individually the organic linkers aid the secondary building unit (SBU) form non-covalent interactions with the surface during the formation of the MOF and facilitate the formation of the MOF on the surface.
The sample comprising the analyte may be prepared experimentally or obtained from the natural environment. In some embodiments, the sample may be obtained from a river, lake, well, pond, stream, ocean, inlet, canal, loch, bay, fountain, sea, or a combination thereof. In other embodiments, the sample may be obtained from tap water, municipal water, municipal wastewater, industrial wastewater, run-off water, ballast water, water treatment water, agricultural water, or a combination of. A liquid sample comprising the analyte can be prepared by treating a solid sample with a liquid to dissolve an analyte. In some embodiments, the solid may be soil, sand, rock, or a combination thereof.
It will be apparent to those of ordinary skill in the relevant art that suitable modifications and adaptations to the methods, processes, and applications described herein can be made without departing from the scope of any embodiments or aspects thereof. The methods provided are exemplary and are not intended to limit the scope of any of the specified embodiments. All of the various embodiments, aspects, and options disclosed herein can be combined in any variations or iterations. The scope of the methods and processes described herein include all actual or potential combinations of embodiments, aspects, options, examples, and preferences herein described. The exemplary methods described herein may substitute any component disclosed herein, or include any component disclosed elsewhere herein. Should the meaning of any terms in any of the patents or publications incorporated by reference conflict with the meaning of the terms used in this disclosure, the meanings of the terms or phrases in this disclosure are controlling. Furthermore, the foregoing discussion discloses and describes merely exemplary embodiments. All patents and publications cited herein are incorporated by reference herein for the specific teachings thereof.
Various embodiments and aspects of the inventions described herein are summarized by the following clauses:
High adsorption capacity for perfluoroalkyl or polyfluoroalkyl substances (PFAS) is crucial for the dual functionality of MOF of detecting and removing PFAS. Described herein is the design and synthesis of a nonfluorinated, water-stable MOF with hydrophobic 3,4,9,10-Perylenetetracarboxylic diimide (PDI) as the bridging ligand (
H2L. 21,6,7,8-tetrachloroperylene-3,4,9,10-tetracarboxylic acid dianhydride (1.00 g, 1.89 mmol), 4-amino-2-methylbenzoic acid (2.85 g, 18.9 mmol), and propionic acid (25 mL) were stirred at 150° C. for 20 h. The resulting mixture was then allowed to cool to room temperature, followed by an addition of water to the mixture. The resulting precipitate was filtered, washed with a mixture of methanol and water (1:1), and dried under vacuum to obtain an orange solid. This solid was then subjected to recrystallization twice with DMF, resulting in the final desired product (orange powder). Yield: 1.06 g (70%).
1H NMR (400 MHz, DMSO) δ 8.61 (s, 4H), 7.98 (d, 2H), 7.35 (m, 4H), 2.59 (s, 6H). ESI-MS (m/z): [M−H+] Calcd. 793.98, found 792.97. The NMR and mass spectra of H2L ligand are shown in
U-1. A mixture of ZrCl4 (29 mg, 0.125 mmol), H2L ligand (50 mg, 0.0625 mmol) and trifluoroacetic acid (TFA) were dissolved in 15 mL of N,N-dimethylformamide (DMIF) by sonication for 10 min. The resulting dark red solution was transferred into a teflon liner and heated at 100° C. for 24 h. After being cooled to room temperature, the red powder was collected by filtration and washed with large volumes of DMF and acetone. After filtration, the MOF sample was dried in an oven.
Physical Measurements. Fourier transform infrared (FT-IR) spectra were collected in the region of 440-4000 cm-1 with a Nicolet iS50 FT-IR spectrometer. Thermogravimetric analyses (TGA) were carried out with a TA Instruments Discovery SDT 650 thermogravimetric analyzer in a temperature range of 30-700° C. in an air atmosphere. Ambient-temperature powder X-ray diffraction (PXRD) patterns were measured on a Bruker D2 Phaser X-ray diffractometer operated at 30 kV and 10 mA using Cu Kα (λ=1.5406 Å) radiation. The nitrogen sorption isotherms up to 1 bar were recorded using a Micromeritics 3Flex gas sorption analyzer at −196° C. Before the sorption measurement, the compound was degassed at 80° C. for 24 h under dynamic vacuum. Steady-state fluorescence studies were carried out by using an Agilent Cary Eclipse fluorescence spectrophotometer. Fluorescence images were taken with a Leica DMi8 fluorescent microscope. NMR data were recorded on a Varian Mercury 400 MHz spectrometer. X-ray photoelectron spectroscopy (XPS) measurements were performed using a Kratos Axis Ultra DLD x-ray spectrometer. Thermo Scientific Advantage Data System software was used for data analysis with the C 1s reference peak at 284.8 eV. A Bruker maXis II ETD Q-TOF LC/MS instrument was used to obtain high resolution ESI MS data. Scanning electron microscopy (SEM) images were obtained on an FEI Nova NanoSEM™ scanning electron microscope.
Filter paper-based PFOA detection protocol. The U-1 MOF was coated on Whatman filter paper (˜1 cm×1 cm) by immersing the paper in MOF suspension made in ethanol, followed by oven drying. The process was repeated three times to increase MOF loading on the paper strip. The MOF loading amount was ˜5 mg/cm2 (measured by taking weight before and after loading). L of various low concentration (10-50 nM) solutions of PFOA were added to paper strips (˜1 cm×1 cm) and solvents subsequently dried. The process was repeated five times (total volume added 75 μL) to ensure adequate accumulation of PFOA. Finally, 10 μL DMF was added to the PFOA accumulated paper and emission intensity was measured.
Digestion protocol of the MOF sample for recording 19F NMR spectrum. 10 mg of MOF sample was added to 0.5 mL of DMSO-d6. To this solution, 100 μL of saturated solution of tripotassium phosphate in D2O was added. After incubating for 30 min at 70° C., the MOF sample became dissolved and the organic phase was filtered. Clear red colored solution was analyzed by 19F NMR spectroscopy.
Pawley refinement. The powder X-ray diffraction (PXRD) pattern of U-1 was measured in a reflection geometry using CuKα1 radiation and indexed with the help of STOE WinXPow software (Found: I-centered cell, a=b=18.885(13) Å and c=83.056(22) Å with a space group, I41/a). In U-1, the model of the methyl functionalized PTCDI ligand molecule was similar to the ligand molecule used previously by Lü et al. to make Zr-PDI MOF. This structural simulation and refinement are necessary since the ligand molecule in U-1 has a methyl-functional group and trifluoroacetic acid (TFA) was used as a modulator. The simulated structure was obtained by imposing the structure of Zr-PDI, converting the ligand molecule, and subsequently optimized by force-field calculation using the universal force field as implemented in the Materials Studio software. An attempted full Pawley refinement of this model was not possible, which may be due to the length of the ligand molecule, the large unit cell and the low number of reflections above 20°. Some relevant cell parameters for the modelling are summarized in Table 1 and the final plot is shown in
Sensing experiments for PFAS. The suspension of activated U-1 MOF was prepared by dispersing 6 mg of MOF powder in 3 mL of DMF. The mixtures were sonicated for 30 min. to create homogeneity throughout the dispersion before fluorescence measurements were taken. 0.2 mL of the as-prepared stock solution were mixed with 2.8 mL of water/DMF (60/40 v/v) in a quartz cuvette (final MOF concentration: 0.13 mg/mL). The emission spectra of the U-1 MOF suspension were obtained at an excitation wavelength (λex) of 490 nm. The analytes and interferents used for the sensor testing experiments were PFOA, PFOS, octanoic acid, lauric acid, trifluoracetic acid (TFA), and cetyltrimethyl ammonium bromide (CTAB), for which 10 mM stock solutions were prepared in water. Selected PFAS and other interferents were added gradually into the U-1 suspension, and the mixture was thoroughly mixed before recording the fluorescence spectra. The spectra were recorded three times for each sample and the averaged data were plotted to ensure accuracy and reliability.
Filter paper based PFOA detection. The U-1 MOF was coated on Whatman filter paper (˜1 cm×1 cm) by immersing the paper in MOF suspension made in ethanol, followed by oven drying. The process was repeated three times to increase MOF loading on the paper strip. The MOF loading amount was ˜5 mg/cm2 (measured by taking weight before and after loading). 15 L of various low concentration (10-50 nM) solutions of PFOA were added to paper strips (˜1 cm×1 cm) and solvents were subsequently dried. The process was repeated five times (total volume added 75 μL) to ensure adequate accumulation of PFOA. Finally, 10 μL DMF was added to the PFOA accumulated paper and emission intensity was measured.’
Regeneration of MOF. After each consecutive sensing cycle, the MOF suspension was carefully transferred into a centrifuge tube. The solution was then subjected to centrifugation for 10 minutes at 4000 rpm. The supernatant solution was decanted, and 10 mL of a 30/70 v/v mixture of 0.1 M HCl and methanol was added. This mixture was sonicated for 30 minutes before being centrifuged at 4000 rpm for 10 minutes to collect the MOF particles. This process was repeated three times. The MOF was then washed twice with deionized water followed by acetone and collected via centrifugation. The regenerated MOF was dried in a vacuum oven at 60° C. before the next sensing experiment.
Quantum Yield Calculation. The fluorescence quantum yield of the U-1 MOF, before and after PFOA sensing, was evaluated by Parker-Rees method using Rhodamine 6G as a standard fluorophore. The Parker-Rees equation can be written as follows:
Where (s represents the quantum yield of the reference compound (Rhodamine 6G, with a value of 0.95) and (Du denotes the quantum yield of the MOF sample. As and Au stand for the absorbances of Rhodamine 6G and the MOF sample at the excitation wavelength (490 nm), respectively. To mitigate the reabsorption of fluorescence light passing through the samples, their absorbance maxima were maintained below 0.1. Fs and Fu denote the integrated fluorescence intensity areas of Rhodamine 6G and the MOF sample when excited at the same wavelength, respectively. The refractive indices of the solvents for the MOF sample suspension and Rhodamine 6G are denoted by nu and ns respectively.
Initially, the synthetic procedure reported by Lü et al. (Lü, B., et al. Nat. Commun. 2019, 10 (1), 1-8) was used. In the Lü et al publication acetic acid as a modulator was used to prepare a perylene diimide based MOF (Zr-PDI). Unfortunately, no crystalline MOF material was obtained for the PDI-based ligand (H2L) using the Lü et al. procedure. As a result, alternative synthesis conditions were explored using different zirconium salts (ZrCl4 and ZrOCl2·8H2O) and dimethylformamide (DMF) as a solvent. Different temperatures and reactions times were evaluated. Various modulators, such as benzoic acid, acetic acid, formic acid, proline, and trifluoroacetic acid were also tested. Parameter testing was performed to increase the crystallinity of the MOFs (Table 2).
Optimized synthesis conditions were achieved by using ZrCl4 as the metal salt, trifluoroacetic acid as the modulator, and DMF as the solvent. Crystalline powder of U-1 MOF was obtained by heating the reaction mixture for 24 hours at 100° C. The significant difference in synthesis protocol between U-1 and the previous Zr-PDI MOF is the methyl modification at the benzoic group of the PDI ligand, which changes the local hydrophobicity around the metal cluster.
The solvothermal reaction between H2L (
The phase purity of U-1 was confirmed by the XRPD measurement. The as-synthesized MOF material showed a good semblance with the simulated XRPD pattern (
MOFs constructed with large ligand molecules tend to undergo pore collapse upon solvent removal. Permanent porosity is a crucial property for current MOFs constructed with PDI ligands (length >24 Å). N2 sorption experiments were conducted to check the permanent porosity of the activated U-1 MOF. The N2 sorption isotherms of U-1 are in agreement with IUPAC classifications, following a type I behavior (
To verify the chemical stability of U-1 MOF, the powder material was immersed in different kinds of liquids (e.g., ethanol (EtOH), acetonitrile, tetrahydrofuran (THF), and dimethylformamide (DMF) etc.) overnight. The MOF material was then recovered by centrifugation, and the XRPD patterns were recorded. The XRPD patterns of the solvent treated U-1 remained almost unchanged compared to the untreated sample (
PDIs have received considerable attention as fluorophores due to their high photochemical and thermal stability in ambient conditions. Based on the high structural tunability at the bay- and imide-positions, numerous molecules of PDI-based materials have been developed as chemical sensors. The PDI based fluorophore shows interesting emissive behavior in a fully dissolved state in solution. A strong tendency towards intermolecular π-π stacking of PDI molecules leads to aggregation-caused quenching (ACQ), which decreases the emission in an aggregated or solid state. Such ACQ phenomenon restricts the application of PDIs as a solid-state sensor material. Prevention of close π-π stacking in solid state PDI is challenging. In metal organic frameworks, the ligand molecules can self-assemble via metal coordination in a well-defined manner in the crystal system. This is unique and not applicable to other types of self-assembly processes. The formation of PDI ligand-based MOF could be beneficial to mitigate the ACQ effect on PDI fluorophores.
To verify this hypothesis, fluorescence microscopy measurements were performed on the free ligand H2L and U-1 MOF deposited on a glass substrate (
The UV-Vis spectrum of U-1 MOF shows two strong absorption bands near 543 nm and 496 nm, with a broad shoulder peak around 456 nm (
The interesting fluorescence behavior of the current MOF in both solid and dispersed states provided motivation to investigate the impact of solvents on the MOF's emission. The fluorescence emission intensity of the MOF is notably reduced in water, the most polar solvent among those tested, as shown in
The photophysical properties and porous nature of PDI-based MOF descried herein led to the investigation of response of the MOF towards PFOA. The Zr-PDI MOF, recently reported, does not possess the methyl groups at the phenyl moiety. These pre-functionalized hydrophobic groups are especially critical for enhancing the binding and detection of hydrophobic target analytes, like PFAS compounds, leveraging the strong hydrophobic interactions. The use of a methylated ligand also helps maintain hydrophobic pore walls of MOF, thus enhancing water stability, and helping preserve the porosity that is crucial for the internal diffusion of PFAS. Additionally, the bridge ligand being a non-fluorinated ligand makes the MOFs described herein less toxic compared to other hydrophobic, water-stable MOFs.
The fluorescence spectra of the dispersed MOF powder in water/DMF (60/40: v/v) was recorded with incremental additions of aqueous PFOA solution (
The UV-Vis spectrum of the MOF suspension was recorded post-PFOA sensing experiment and compared with the spectrum of the MOF suspension prior to PFOA addition. After PFOA sensing, the UV-Vis spectra of U-1 MOF retain about the same shape with the two prominent peaks around 543 and 496 nm slightly blue shifted to 540 and 492 nm, respectively (
To assess the response time of U-1 MOF for detecting PFOA, time-dependent experiments were carried out with various concentrations of PFOA solutions (
To examine the selectivity of U-1 towards PFOA, another common PFAS compound, PFOS was also tested under the same conditions. Surprisingly, only a slight turn-on response was observed for PFOS (
To further examine the sensitivity of U-1 MOF, another set of experiments were performed where the interferent compounds were added together with PFOA in equal amount. As depicted in
The sensing experiments were conducted in a mixture of water and DMF, while the PFOA analyte was introduced solely in water, to examine the impact of increasing the water content in the sensing system. To assess the effect of water content on the emission behavior, fluorescence spectra of the MOF were measured using different ratios of water to DMF in solution. As illustrated in
Reusability is a crucial parameter in sensor development, ensuring prolonged usage and cost-effectiveness. The reusability of the current MOF sensor was tested for up to five cycles following sensing experiments. After each sensing cycle, the MOF was recovered by washing with a 30/70 (v/v) binary mixture of 0.1 M HCl in methanol. As illustrated in
To estimate the limit of detection (LOD), the emission intensity of U-1 MOF dispersed in water/DMF (60/40 v/v) was measured at increasing concentrations of PFOA in the range of 0-M. As shown in
The identification of PFOA in the blood of individuals without occupational exposure to the chemical initially pointed to residential drinking water as the primary source of human exposure. Therefore, it is necessary for a PFOA sensor to be capable of operating effectively in complex, real-world systems. Sensing experiments for PFOA were conducted using tap and drinking water samples to address this need for reliability in diverse environmental matrices. The titration plot depicted in
Mechanisms of PDOA Binding with U-1 MOF
From the fluorescence sensing response obtained above for PFOA in comparison with other analytes, the binding of PFOA within MOF depends on both the complexation with the metal ion and the hydrophobic interaction with the PDI ligands. The strong binding of PFAS results in conformational change of the π-conjugation structure of PDI backbone, particularly the dihedral twisting angle around the four chloro-moieties. Such conformational change leads to an increase in emission intensity (vide infra). There is a possibility that the intercalation of PFOA may destroy the intrinsic structure of U-1 MOF, thus releasing the free ligand of PDI, leading to fluorescence turn-on. To exclude this possibility, the structural integrity of U-1 MOF powder was verified by PXRD measurement before and after the PFOA treatment. Almost no change in PXRD patterns was observed for the MOF sample after being tested with PFOA (
19F-NMR spectroscopy was also used to examine any inclusion of PFOA molecules inside the MOF after the sensing test. The MOF was collected after the sensing experiment. and digested with tripotassium phosphate. The 19F NMR spectrum of the digested MOF was recorded and compared with pure PFOA. As depicted in
XPS was employed to analyze the surface changes of U-1 MOF upon PFOA adsorption. The XPS survey scans of U-1 MOF before and after test with PFOA, and pure PFOA are shown in
The analysis reveals that U-1 MOF has characteristic Zr 3d peaks located at 183.71 and 186.11 eV, indicating the presence of Zr4+. Moreover, the F is binding energies of the MOF were found to be at 689.0 and 687 eV. Upon adsorption with PFOA, a shift in the F is binding energies was observed, with values of 688.91 and 685.60 eV, which agrees with the chemical changes induced in the trifluoromethyl groups due to adsorption in the MOF. Interestingly, the characteristic Zr 3d binding energies also shifted from 183.71 and 186.11 eV to 184.05 and 186.30 eV, respectively, indicating a perturbation in the coordination environment induced by PFOA binding (Table 5). Binding to a fluorinated compound causes the loss of electron density over zirconium, which in turn increases its 3d3/2 and 3d5/2 binding energies in the MOF. All the data presented confirm the successful adsorption of PFOA into the MOF.
The fluorinated hydrophobic chain, along with polar carboxylic acid group, plays a pivotal role for the selective sensing of PFOA. An additional fluorescence experiment was performed to support this hypothesis. A series of short-chain perfluoroalkyl carboxylic acids (PFCAs) were treated with U-1 MOF suspension and changes in emission spectra were recorded. As depicted in
Increasing binding affinity for longer-chain perfluoroalkyl carboxylic acids (PFCAs) compared to short chain PFCAs was observed in U-1. A combined experimental and theoretical study was undertaken to understand the molecular-level interactions between MOF and PFOA, aiming to gain insights into the sensing mechanism. It is known that PFOA exhibits significantly stronger acidity than its corresponding fatty acid, implying that the interaction between PFOA and MOF could entail a covalent interaction. The shift in Bragg diffraction peak positions towards lower 20 values after PFOA sensing was confirmed by PXRD analysis (
DFT calculations were further employed to investigate the origin of PFOA interactions with MOF. PFOA molecules were introduced at the adsorption sites (Zr6 SBU) in a model of U-1 that was previously identified and confirmed by XPS and X-ray structure refinement. The resulting optimized structure of PFOA@U-1 is displayed in
Described herein is the synthesis and systematic exploration of robust, fluorescent PDI-based MOF, namely U-1, for the detection of PFOA through a fluorescence turn-on response. The tetrachloro-substitution increases the solubility of the PDI ligand during MOF synthesis, whereas the judicious incorporation of methyl groups increases the hydrophobicity around the Zr6 SBUs in the MOF. This minimizes the interaction with water molecules, which in turn helps enhance the stability of the MOF in water. Zirconium metal ion were selected for the MOF synthesis because of its binding affinity towards PFAS molecules, like PFOA, that contain carboxylic groups. The PDI-based MOF showed a rapid fluorescence turn-on response towards PFOA in aqueous solutions. Although similar in structure, PFOS did not demonstrate a significant turn-on response compared to PFOA. This reusable MOF sensor has the ability detect the presence of PFOA in real water samples, including tap and drinking water. The rapid turn-on sensing via a MOF-PFOA complex formation mechanism may soon lead to this material being an efficient dual sensor and absorber for PFAS.
The results described herein reveal that U-1 MOF exhibits outstanding stability in various chemical environments. The fluorescent sensing of U-1 MOF is relatively selective toward PFOA as tested in solution phase. The same fluorescence turn-on response was also observed for the solid phase by depositing the MOF onto a filter paper. Built upon the effective SPE effect, the LOD of the film sensor was pushed down to 3.1 nM. Detailed structural analysis suggests that the fluorescence turn-on is predominated by two cooperative interactions, the complexation between the carboxylic group of PFOA and the zirconium metal center, and the hydrophobic interaction between the fluorinated alkyl chain of PFOA and the PDI ligand. The work presented herein showcases the great potential of PDI-based MOFs as fluorescent probes for the sensitive and selective detection of PFAS, for which the detection selectivity can be further improved by tuning the ligand structure and the porosity of MOFs.
High adsorption capacity for perfluoroalkyl or polyfluoroalkyl substances (PFAS) is crucial for the dual functionality of MOF of detecting and removing PFAS. Described herein is the design and synthesis of a non-fluorinated MOFs contain UiO-66-based bridging ligands that display adsorption with enhanced adsorption capacity as compared to commercial granular activated carbon (GAC), a common type of sorbent for PFAS and other water pollutants.
UiO-66-N(CH3)3+. UiO-66-NH2 was performed by the literature procedure, as reported by Dalapati, R. and Biswas, S. (Dalapati, R. and Biswas, S., Sensors and Actuators B: Chemical, 2017, 239, 759-767). UiO-66-NH2 (0.5 g) was added in a mixture of CH3I (3 mL) and toluene (15 mL). The mixture was transferred into Teflon lined autoclave and heated at 80° C. for overnight for the partial quaternization process. The resulting dark yellow product, denoted as UiO-66—N(CH3)3+, was subsequently recovered through filtration, subjected to methanol washing, and ultimately dried at 60° C. This process substantially diminishes the reaction duration in comparison to earlier reported methodologies, which typically required a period of three days.
MOF UiO-66-N(CH3)3+. UiO-66-NH2 MOF was further modified via a previously reported procedure with modifications (Xiaocong, T. et al., Chem. Commun., 2023, 59, 4507-4510). UiO-66-NH2 (0.5 g) was added in a mixture of CH3I (3 mL) and toluene (15 mL). The mixture was transferred into Teflon lined auto-clave and heated at 80° C. for overnight for the partial quaternization process. The resulting dark yellow product, denoted as UiO-66-N(CH3)3+, was subsequently recovered through filtration, subjected to methanol washing, and ultimately dried at 60° C.
A completely dried sample (50 mg) of UiO-66-N(CH3)3+ was soaked in the 5 mM aqueous solution (50 mL) of sulforhodamine B (SRB) dye for 1 h. The resulting solid was washed vigorously with water until no fluorescence was observed in supernatant solution and isolated via centrifugation.
Adsorption studies were performed by adding ˜10 mg of UiO-66-N(CH3)3+ to 20 mL of 1000 ppm PFOA solution in a polypropylene centrifuge tube at room temperature. The solution was centrifuged after 30 min of stirring and 700 μL of solution was transferred to NMR tube. A 50 μL TFA/D2O was added as internal standard to the NMR tube before analysis. Quantitative 19F NMR (
Here, [PFOA] and [TFA] are the respective concentrations, IPFOA and ITFA are the integrals from the 19F-NMR spectrum, respectively, and NTFA and NPFOA are the number of F atoms that give rise to each NMR signal, respectively. The resonance at −75.33 ppm is due to the —CF3 group of TFA, while the resonance at −80.82 ppm arises from the —CF3 group of PFOA. The difference in PFOA concentration before and after adsorption is assumed to be adsorbed by UiO-66-N(CH3)3+.
Current post-synthetically modified UiO-66-N(CH3)3+ MOF has similar structure like parent UIO-66-NH2. The structure consists of an inner Zr6O4(OH)4 core in which the triangular faces of the Zr6-octahedron are alternatively capped by μ3-O and μ3-OH groups. All the edges of the polyhedron are connected by carboxylate groups (μ2-(CO2)) from dicarboxylic acids, forming a Zr6O4(OH)4(CO2)12 cluster. Each zirconium atom is thus eight-coordinated, adopting a square-antiprismatic coordination geometry. The ligands are bonded exclusively through oxygen atoms. One square face of the antiprism is constituted by oxygen atoms from the carboxylate groups, while the other square face comprises oxygen atoms from the μ3-O and μ3-OH groups. The structure is shown by
The synthesis of UiO-66-NH2 MOF was first confirmed by powder XRD analysis. Further modification of MOFs was also confirmed by XRD analysis. As shown in
The porosity of post synthetically modified cationic MOF was also measured by BET surface area analysis. Data shown in
Characterization by 1H NMR found that UiO-66-N(CH3)3+ contains three types of methylated ligands, including secondary, tertiary, and quaternary amines. As the 1H NMR spectrum of UiO-66-NH2 depicted in
The adsorption capacity of PFOA was tested by cation modified MOF for the first time. The adsorption capacity was quantified by 19F-NMR spectra analysis as described earlier. In addition to cationic MOF, other well-known MOFs and commercially available activated carbon were also used to compare the PFOA uptake capacity (
This application claims priority to U.S. Provisional Patent Application No. 63/470,564, filed on Jun. 2, 2023, the entire contents of which are fully incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63470564 | Jun 2023 | US |
