Glass container coated with a metal-organic structure on the inside

Abstract

The present invention relates to a device consisting of a glass vessel, the inner wall of which is modified after successive activation, silanization and amidation reactions to accommodate a porous crystalline coating, the coating having an atomic sequence -Si-ORM-MOF, covalently bonded in a radially inverse manner to the inner wall of the vessel, where R is (A) -Si-(CH2)3-NH-CH(=O)-(CH4)-COO-, (B) -Si-(CH2) n -NH-CH(=O)-(CH2)2-(C2HN3)-(CH2) n -(C6H4)-COO-, (C)-Si-(CH2) n -O-CH2-CH(-OH)-CH2-NH-(CH2) n -(C6H4)-COO-, (D)-Si-(CH2) n -S-(CH2)2-(CH2) n The MOF may be -(C6H4)-COO-, where M is a metal that varies depending on the type of MOF. The vessel may be used for the extraction and preconcentration of analytes in samples of various nature, from environmental to biological. The invention also relates to its use for the administration of drugs or for coloring or flavoring beverages.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of microextraction devices for chemical analysis, drug administration, and the agri-food industry. BACKGROUND ART

[0002] Metal-organic frameworks (MOFs) are crystalline materials having an ordered three-dimensional structure formed by the coordinative bonding of metal clusters or ions and organic ligands, as described in Spanish Patent Application Publication No. ES2356130. Among many properties, they are noted for having the largest surface area known to date, uniform porosity, and high synthetic versatility (Science 2013, 341, 1230444). All of these properties make them very interesting adsorbents for the development of analytical microextraction strategies.

[0003] Thin-film microextraction (TFME) is an analytical extraction and pre-concentration technique based on the use of a device composed of a thin layer of extraction material coated on a solid support (such as paper or fabric) or a membrane without any solid support. This technique is conceived as an alternative form of solid-phase microextraction (SPME) proposed by Professor Pawliszyn in the late 1980s (ES2056644T3), which results in a larger surface area / volume ratio of the final device, improving analytical sensitivity without increasing extraction time.

[0004] In 2001, Wilcockson et al. (Environ. Sci. Technol. 2001, 35, 1425-1431) published the first paper on TFME, describing the use of five ethylene vinyl acetate (EVA) coated glass sheets exposed in the upper space of a container. TFME devices were applied to the extraction of organic compounds from biological tissues. However, it wasn't until 2003 that Bruheim et al. (Anal. Chem. 2003, 75, 1002-1010) evaluated the advantages offered by TFME compared to SPME. They presented a device with a polydimethylsiloxane (PDMS) membrane wrapped around a stainless steel rod. They compared the results of polycyclic aromatic hydrocarbon (PAH) analysis with those obtained using SPME with 100 μm thick PDMS fibers. Indeed, TFME was demonstrated to function as an alternative form of SPME for achieving higher extraction efficiency without increasing extraction time. Since then, a variety of applications using all types of TFME devices have emerged. Here are some related examples.

[0005] U.S. Patent No. 5,827,944 describes a sample preparation apparatus consisting of a vial-shaped container with an Eppendorf-like conical base, the bottom or cap of which is coated with a stationary phase. This apparatus works by pouring a sample into the vial, which then transfers compounds present in the sample to the stationary phase, which are then introduced into a gas chromatograph by thermal desorption and aspiration for analysis.

[0006] The paper "Chem.Cent.J. 2008, 2, 8" describes glass vials prepared by dispersing polymers in commercially available adhesives and coated with PDMS (3-12 μm thick) to ensure adhesion. To extract and pre-concentrate seven types of PAHs, soil samples were filled into the vials and left to stand for 5 days with stirring.

[0007] The paper "J.Chromatogr.A 2009, 1216, 7553-7557" first describes the "Vial Wall Adsorption Extraction" (VWSE) technique for extraction and pre-concentration. To fabricate this device, PDMS is first synthesized in small 1.5 mL and 2 mL vials using SILPOT 184 and a crosslinking agent. Three alternatives are proposed: (1) placing the PDMS precursor in the vial and carrying out the polymerization reaction, (2) inserting a V-shaped object before the reaction, and (3) rotating the vial horizontally while the reaction is occurring. This application was for measuring progesterone in human serum.

[0008] In the paper "Eur.J.Pharm.Biopharm. 2013, 85, 756-764," borosilicate vials are coated with a dendritic polyglycerol-based polymer modified with triethoxysilyl. The surface is activated with piranha solution, washed with water, and then an ethanol solution of the polymer is added. These devices are used to control the absorption of nonspecific substances in tests for measuring the concentration of specific proteins.

[0009] Spanish Patent Application Publication No. 2799351 describes a metal-organic structure on a nickel / titanium support connected by APTES, specifically an SPME device with a CIM-80(AI) stationary phase. This device was used for the extraction and pre-concentration of PAHs in water, resulting in improved extraction yields of commercially available fibers.

[0010] International Publication No. 2021 / 003316 discloses a thin PDMS coating for extraction vials. In the TFME method, contaminants are absorbed or adsorbed by the PDMS coating. The supernatant is discarded, and volatile analytes present in the upper space are trapped in the coating by raising the temperature, facilitating their transfer to an analytical instrument, which is a gas chromatograph coupled with a mass spectrometer.

[0011] The paper "Anal.Chim.Acta 2021, 1152, 338226" describes the use of a sampling bottle with an inner wall coated with PDMS and divinylbenzene (DVB) as a device for the extraction and pre-concentration of BTEX in water samples. This device is fully portable and can be combined with instruments for on-site analysis.

[0012] As with all variations of click chemistry, the use of silane derivatives for surface functionalization is a well-known and widely used technique. Some of the most important literature in this regard is as follows:

[0013] The paper "Chem.Mater. 2003, 15, 1132-1139" established a precedent for the production of amino-functionalized silica surfaces with clear and uniform reactivity.

[0014] Chinese Patent Application Publication No. 105694051 presents a polymer membrane produced by crosslinking a MOF using a thiol-alkene click reaction. The membrane thus produced can be used for the separation of substances.

[0015] U.S. Patent No. 8,148,287 presents a method for depositing a catalyst onto a siliceous mesocellular foam surface by an azide-alkyne type click reaction.

[0016] In the paper "Anal.Chim.Acta 2019, 1060, 103-113," the functionalization of a flat glass support for immobilizing oligonucleotides and proteins via epoxide cleavage and alkene-thiol reactions using thiol groups is proposed under the name click chemistry.

[0017] The paper "Polymer 2014, 3330-3338" demonstrates a method for functionalizing silicon wafers and glass slides with ionic liquid polymers through alkene-thiol and alkyne-azide reactions.

[0018] The paper "Anal. Chem. 2007, 79, 1661-1667" also proposes the functionalization of glass slides using various organic polymers via alkyne-azide reactions.

[0019] The article "Trends Anal.Chem. 2019, 118, 556-573" reviews the literature on the use of click chemistry in the preparation of novel adsorbents and stationary phases for extraction and chromatography. Click chemistry-type reactions are primarily applied to MOFs to perform post-synthetic modifications or to functionalize MOFs with polymers or biomolecules. [Overview of the project]

[0020] The present invention relates to an apparatus formed from a glass container, the inner wall of which is modified after a series of activation, silanization, and amidation reactions to accommodate a porous crystalline coating. The coating has an atomic arrangement -Si-ORM-MOF and is covalently bonded in reverse radially to the inner wall of the container, where R is an intermediate compound defined below and M is a metal dependent on the metal-organic structure (MOF).

[0021] There are four possible methods for immobilizing MOFs onto containers, all of which are based on the functionalization of silanols covalently bonded to the glass surface.

[0022] This invention is the first to use silane derivatives and click chemistry to functionalize glass surfaces, enabling the fixation of metal-organic structures.

[0023] These various anchors are executed as the result of the following intermediate compounds.

[0024] [ka]

[0025] M can be any one of the metals Zr, Ti, Al, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mg, Ca, Sc, and Sr, which is determined by the type of MOF in the coating. The MOF can be any of those described below, preferably including, but not limited to, UiO-66(Zr), UiO-66(Zr)-NH₂, UiO-66(Zr)-NO₂, MIL-101(Fe), MIL-101(Fe)-NH₂, MIL-100(Cr), CIM-80(Al), PCN-250(Fe₂Co), PCN-250(Fe), UiO-67, HKUST-1, DUT-52, DUT-67, and modified forms thereof having a terminal amino group or azide group. Furthermore, other MOFs named in this way are not excluded, as experimental results show that the proposed invention functions regardless of the selected MOF and is generally applicable.

[0026] The basis of the methodology of the present invention is the use of click chemistry for covalently bonding MOFs to the glass surface. In this sense, the present invention first performs carboxyl functionalization with terephthaloyl chloride to form an amide from APTES (3-aminopropyltriethoxysilane) bonded to the glass surface, then reaches the intermediate compound (A), and subsequently grows the MOF (Figure 2).

[0027] Intermediate compound (B) is obtained after the alkyne-azide click reaction, preferably N-(3-(trimethoxysilyl)propyl)propiolamide (AMIPTES) is bound to the MOF modified after synthesis with 4-azidopropylbenzoic acid, but the use of this version is not limited to various steps using N-hydroxysuccinimide, 1-ethyl-3(3-dimethylaminopropyl)carbodiimide, and 4-pentynoic acid (Figure 3).

[0028] Intermediate compound (C) is generated from an epoxide ring-opening click reaction using GLYMO (3-glycidyloxypropyltrimethoxysilane) and the MOF modified after synthesis with 4-aminoethylbenzoic acid (Figure 4).

[0029] Intermediate compound (D) is obtained after a thiol-alkene click reaction using a MOF that has been modified after synthesis with 3-mercaptopropyltriethoxysilane and 4-vinylbenzoic acid.

[0030] The production method of the present invention covalently bonds the metal-organic framework (adsorbent) to the glass substrate to prevent peeling and deterioration during use. The surface modification is performed in a reverse radial manner, starting from the glass of the container, with material added to the interior of the container.

[0031] The glass vial is used as a TFME device for sample preparation to perform qualitative or quantitative analysis of trace components in samples of environmental origin, biological origin, and the like. This container is capable of extracting and pre-concentrating target analytes of samples (water, urine, saliva, etc.), and subsequent analysis is performed by either liquid chromatography (after liquid desorption with a suitable solvent compatible with the measuring instrument) or gas chromatography (by thermal desorption).

[0032] With the apparatus of the present invention, the sample processing process is far simpler than any of the current methods, as the container collects, extracts, and pre-concentrates the sample in one step, and analyte desorption is very simple, with high compatibility with conventional laboratory analytical apparatuses. Since the device can be manufactured using any MOF, it can be selected as needed depending on the specific application for which the container is dedicatedly used.

[0033] There is no commercially available apparatus similar to the one presented herein, but the most similar among apparatuses for sample pre-concentration and pretreatment are apparatuses based on solid-phase microextraction (SPME) or thin-film microextraction (TFME). When comparing the present invention with these devices, errors may arise because the methods of use are completely different. In commercial SPME and TFME devices, the device is immersed in the sample or used in the headspace, and then the analyte is eluted with a solvent compatible with the chromatography method or directly injected into gas chromatography. In the device of the present invention, the sample is added to the device.

[0034] The extraction method disclosed in this invention is extremely simple and superior to other conventional apparatuses because it allows the addition of the sample and desorption solvent in the same container without requiring complex intermediate steps.

[0035] Furthermore, alternative uses of the present invention have been proposed for drug administration or for coloring and flavoring beverages.

[0036] (Drug administration) Using a container coated on the inside with an adsorbent allows for the storage of a substance and its return to the medium in a specific dose. In this sense, drugs can be filled into porous materials by adsorption of an ethanol solution. Even in an empty container, by pouring water into a container that already contains drugs on its walls, drug desorption to the drug / MOF is initiated at a specific rate, allowing for administration in a relatively simple and visually acceptable manner, even in the event of drug rejection.

[0037] (Coloring or flavoring of beverages) Following the same methods as in drug administration, the container allows for the incorporation of coloring or flavoring molecules into the metal-organic structure. In this sense, during beverage serving and when filling the container with beverage, desorption and adsorption of molecules trapped in the porous material occur, leading to the coloring, flavoring, or aromatization of the beverage.

[0038] The figures are included for the purpose of illustrating the most representative aspects of the present invention. The examples shown below are for illustrative purposes only and do not limit the present invention. [Brief explanation of the drawing]

[0039] [Figure 1] This is an overall diagram of the device. I = screw cap, II = uncoated upper space, and III = inner wall coated with MOF. [Figure 2]The following are representative diagrams of the chemical reactions in the first and last embodiments of the present invention. Step 1: Surface activation, Step 2: Silanation reaction with terminal amino groups, Step 3: Reaction to form amides and expose terminal carboxyl groups, Step 4: Solventrally heated MOF growth. [Figure 3] A representative figure of the second embodiment of the present invention is shown. Step 1: Surface activation, Step 2: Silane reaction by terminal amino group, Step 3: Reaction to form an amide and expose terminal alkyne group on the surface, Step 4: Alkyne-azidocrick reaction using an MOF having terminal azide group. [Figure 4] A representative figure of the third embodiment of the present invention is shown. Step 1: Surface activation, Step 2: Silane reaction by terminal epoxide groups, Step 3: Epoxide cleavage reaction using an MOF having terminal amino groups. [Figure 5] This image shows a scanning electron microscope (SEM) image of a cross-section of a glass container coated with MOF MIL-101(Fe). [Figure 6] The extraction efficiencies of a MOF MIL-101(FE) coated device manufactured according to the first embodiment of the present invention are shown, using carbamazepine (a), 4-cumylphenol (b), benzophenone-3 (c), triclosan (d), 4-tert-octylphenol (e), 4-octylphenol (f), chrysene (g), and indeno[1,2,3-cd]pyrene (h). [Figure 7] The extraction efficiency of a MOF UiO-66(zr) coated device using carbamazepine (a), 4-cumylphenol (b), benzophenone-3 (c), triclosan (d), 4-tert-octylphenol (e), 4-octylphenol (f), chrysene (g), and indeno[1,2,3-cd]pyrene (h), prepared according to the method described in the fourth embodiment, is shown. [Modes for carrying out the invention]

[0040] However, some illustrative examples that do not limit the present invention are described below.

[0041] In a first embodiment of the present invention, a stationary phase having an inverted radial atomic arrangement, a container-Si-O-Si-(CH2)3-NH-C(=O)-(C6H4)-COO-Fe-MOF, is obtained by four main steps: (1) activation of the silica surface with an alkaline solution, (2) a silanation reaction to generate terminal 3-aminopropyl groups, (3) an amidation reaction to generate terminal carboxyl groups, and (4) growth of MOF MIL-101(Fe) by solvothermal synthesis (Figure 2).

[0042] The method performed inside the glass container is as follows:

[0043] 1. Activate the container by adding a 1M NaOH aqueous solution at 25°C for 24 hours, then wash it thoroughly with water, and finally add a second 1M HCl solution at 25°C for 30 minutes.

[0044] 2. The silanization of the container glass is carried out by adding 3-aminopropyltriethoxysilane (APTES) and leaving it at 60°C for 24 hours to allow the reaction to occur.

[0045] 3. The amidation reaction to generate the terminal carboxyl group is carried out under an inert atmosphere by adding a solution of triethylamine in tetrahydrofuran (THF) to a container, followed by another 0.04 M solution of terephthaloyl chloride in THF. The container is closed and maintained at 60°C for 24 hours until the reaction is complete.

[0046] 4. Finally, add a solution of 0.1 M iron(III) chloride and 0.05 M terephthalic acid in dimethylformamide to the container to incorporate the MOF MIL-101(Fe). Close the container and hold at 110°C for 20 hours until the MOF grows on the inner surface of the container.

[0047] The container thus prepared has a uniform MOF layer of approximately 5 μm on its inner surface (Figure 5). Before using the container, it is advisable to wash it with dimethylformamide and ethanol / acetone, and then heat the opened container under low pressure to remove any DMF residue or reagents trapped in the pores of the material.

[0048] In a second embodiment of the present invention, a stationary phase having an inverted radial atomic arrangement, a container-Si-O-Si-(CH2)3-NH-C(=O)-(CH2)2-(C2N3H)-(CH2)3-(C6H4)-COO-Zr-MOF, is obtained by four steps: (1) activation of the silica surface with an alkaline solution, (2) silanation reaction to generate terminal 3-aminopropyl groups, (3) amidation reaction to generate terminal alkyne groups, and (4) post-synthetic modification of the MOF to incorporate terminal azide groups and alkyne-azide cycloaddition reaction to immobilize the MOF (Figure 3).

[0049] The method performed inside the glass container is as follows:

[0050] 1. Activate the container by adding a 1M NaOH aqueous solution at 25°C for 24 hours, then wash it thoroughly with water, and finally add a second 1M HCl solution at 25°C for 30 minutes.

[0051] 2. The silanization of the container glass is carried out by adding 3-aminopropyltriethoxysilane (APTES) and leaving it at 60°C for 24 hours to allow it to react.

[0052] 3. The amidation reaction to generate terminal alkyne groups is carried out by adding an aqueous solution of N-hydroxysuccinimide (0.002 M), 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (0.124 M), and 4-pentinoic acid (0.071 M) to a container. Close the container and maintain at 25°C for 24 hours until the reaction is complete.

[0053] 4. Modification of the synthesized MOF UiO-66 is carried out by immersion in a DMF solution containing 4-azidopropylbenzoic acid for 24 hours.

[0054] 5. The alkyne-azide cycloaddition reaction is carried out by adding aqueous solutions of CuSO4·5H2O (0.06 M) and sodium ascorbate (0.12 M), followed by the addition of a dispersion of MOF UiO-66 in water and acetonitrile (50:50, v / v). Close the container and allow the reaction to stand at 25°C for 24 hours.

[0055] The container thus prepared has a uniform MOF layer of approximately 0.5 μm on its inner surface. Before using the container, it is convenient to wash it with ethanol / acetone and heat the opened container under reduced pressure to remove any solvent residue or reagents that may remain trapped in the pores of the MOF.

[0056] In a third embodiment of the present invention (Figure 4), a stationary phase having an inverted radial atomic arrangement, a container-Si-O-Si-(CH2)3-O-CH2-CH(-OH)-CH2-NH-(CH2)2-(C6H4)-COO-Zr-MOF, is obtained by three steps: (1) activation of the silica surface with an alkaline solution, (2) a silanation reaction to generate terminal 3-glycidyloxypropyl groups, and (3) post-synthesis modification of the MOF for surface functionalization with terminal amino groups and a ring-opening reaction of an epoxide group to fix the MOF.

[0057] The method performed inside the glass container is as follows:

[0058] 1. Activate the container by adding a 1M NaOH aqueous solution at 25°C for 24 hours, then wash it thoroughly with water, and finally add a second 1M HCl solution at 25°C for 30 minutes.

[0059] 2. The silanization of the container glass is carried out by adding 3-glycidyloxypropyltrimethoxysilane (GLYMO) and leaving it at 60°C for 24 hours to allow it to react.

[0060] 3. Modification of the MOF after synthesis is carried out by immersing the MOF in a DMF solution containing 4-aminopropylbenzoic acid for 24 hours.

[0061] 4. The ring-opening reaction of the epoxide group is carried out by adding a dimethylformamide (DMF) dispersion of the amino-functionalized MOF UiO-66(Zr). Close the container and maintain at 100°C for 24 hours until the reaction is complete.

[0062] The container thus prepared has a uniform MOF layer of approximately 0.5 μm on its inner surface. Before using the container, it is advisable to wash it with ethanol / acetone and heat the opened container under reduced pressure to remove any solvent residue or reagents that may remain trapped in the pores of the MOF.

[0063] In the final embodiment of the present invention (Figure 2), a stationary phase having a radial atomic arrangement, container-Si-O-Si-(CH2)3-NH-C(=O)-(C6H4)-COO-Zr-MOF, is obtained by four steps: (1) silica surface activation with an alkaline solution, (2) silanation reaction to generate terminal 3-aminopropyl groups, (3) amidation reaction to generate terminal carboxyl groups, and (4) MOF UiO-66(Zr) growth by solvothermal synthesis. The method carried out in a glass container is as follows.

[0064] 1. The container is activated by adding a 1M NaOH aqueous solution at 25°C for 24 hours, then washing it thoroughly with water, and finally adding a second 1M HCl solution at 25°C for 30 minutes.

[0065] 2. The silanization of the glass container is carried out by adding 3-aminopropylsilane (APTES) and leaving it at 60°C for 24 hours to allow the reaction to occur.

[0066] 3. The amidation reaction to generate the terminal carboxyl group is carried out under an inert atmosphere by adding a solution of triethylamine in tetrahydrofuran (THF) to a container, followed by another 0.04 M terephthaloyl chloride THF solution. Close the container and maintain at 60°C for 24 hours until the reaction is complete.

[0067] 4. Finally, add a solution of 0.02 M zirconium(IV) chloride and 0.02 M terephthalic acid in dimethylformamide to the container and incorporate the MOF UiO-66(Zr). Close the container and incubate at 120°C for 24 hours until the MOF grows on the inner surface of the container.

[0068] The container prepared in this manner has a uniform MOF layer of approximately 1 μm on its inner surface. Before using the container, it is advisable to wash it with dimethylformamide and ethanol / acetone, and then heat the opened container under low pressure to remove any DMF residue or reagents trapped in the pores of the material.

[0069] Figures 6 and 7 show the results obtained for extraction efficiency when eight different organic compounds (PAHs, phenols, drugs, disinfectants, and solar panels) present at a concentration of 10 ppb in 10 mL of water were analytically measured using the apparatus of the first and last embodiments of the present invention. The process is very simple: the sample is added to the vial, an extraction time of 5 minutes with stirring is used, the supernatant is discarded after extraction, 500 μL of acetonitrile is added to the vial, and a desorption step is performed for 5 minutes under vortex stirring. Centrifugation is not required throughout the microextraction method, ensuring the simplicity of the apparatus for routine use.

Claims

1. A glass vessel comprising, on its inner wall, a coating of formula -Si-O-R-M-MOF covalently bonded in a reverse radial pattern, wherein R is (A) -Si-(CH ２ ) ３ -NH-CH(=O)-(C ６ H ４ )-COO-, (B) -Si-(CH ２ ) ｎ -NH-CH(=O)-(CH ２ ) ２ -(C ２ HN ３ )-(CH ２ ) ｎ -(C ６ H ４ )-COO-, (C) -Si-(CH ２ ) ｎ -O-CH ２ -CH(-OH)-CH ２ -NH-(CH ２ ) ｎ -(C ６ H ４ )-COO-, or (D) -Si-(CH ２ ) ｎ -S-(CH ２ ) ２ -(CH ２ ) ｎ -(C ６ H ４ )-COO-, which is an intermediate compound selected from the group consisting of, n can take a value from 0 to 6, and M is a metal that depends on the type of the metal-organic framework (MOF), the glass vessel.

2. The glass container according to claim 1, wherein M is a metal selected from the group consisting of Zr, Ti, Al, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mg, Ca, Sc, and Sr.

3. The aforementioned MOF is UiO-66(Zr), UiO-66(Zr)-NH ２ UiO-66(Zr)-NO ２ , MIL-101(Fe), MIL-101(Fe)-NH ２ , MIL-100 (Cr), CIM-80 (AI), PCN-250 (Fe ２ The glass container according to claim 2, selected from the group consisting of Co), PCN-250(Fe), UiO-67, HKUST-1, DUT-52, DUT-67, or modified versions thereof having a terminal amino group or azide group.

4. A method for producing a container according to any one of claims 1 to 3, comprising chemically modifying the inner surface of the glass after a series of activation, silanation and amidation reactions, and / or click chemistry reactions.

5. Use of the container according to any one of claims 1 to 3 as a thin-film microextraction (TFME) apparatus for pre-concentration of environmental, biological, agricultural food samples, etc. in (biological) analytical chemistry.

6. Use of the container according to any one of claims 1 to 3 for the administration and dispensing of drugs.

7. Use of the container according to any one of claims 1 to 3 for coloring and flavoring beverages.

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