Glass container with metal-organic framework coated 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, pharmaceutical dosing and the agri-food industry. [Background technology]

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

[0003] Thin film microextraction (TFME) is an analytical extraction and preconcentration technique based on the use of a device composed of a thin layer of extraction material coated with a solid support (such as paper or fabric) or a membrane without any solid support. The technique is considered 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 the 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 head space of a vessel. The TFME device was applied for the extraction of organic compounds from biological tissues. However, it was not until 2003 that Bruheim et al. (Anal. Chem. 2003, 75, 1002-1010) evaluated the advantages offered by TFME compared to SPME. Thereby, they presented a device with a polydimethylsiloxane (PDMS) membrane wound on a stainless steel rod. The analytical results for polycyclic aromatic hydrocarbons (PAHs) were compared with those obtained with SPME using 100 μm thick PDMS fibers. In fact, it was demonstrated that TFME can serve as an alternative form of SPME to obtain higher extraction efficiency without an increase in extraction time. Since then, various applications using all kinds of TFME devices have appeared. Some relevant examples are given below:

[0005] The document US Patent No. 5,827,944 describes a sample preparation device consisting of a container in the shape of an Eppendorf-like conical bottom vial, the bottom or cap of which is coated with a stationary phase, in which the sample is poured into the vial and the compounds present in the sample are transferred to the stationary phase and introduced by thermal desorption and aspiration into a gas chromatograph where the analysis is carried out.

[0006] In the paper "Chem.Cent.J. 2008, 2, 8", they describe glass vials coated with PDMS (3-12 μm thick), which is prepared by dispersing the polymer in a commercially available adhesive, ensuring its adhesion. To perform the extraction and preconcentration of the seven PAHs, the vials are filled with soil samples and left under stirring for 5 days.

[0007] In the paper "J. Chromatogr. A 2009, 1216, 7553-7557" the "Vial Wall Sorption Extraction" technique (abbreviated as VWSE) for extraction and preconcentration is described for the first time. To fabricate this device, PDMS is first synthesized in small vials of 1.5 mL and 2 mL using SILPOT 184 and a crosslinker. Three formal 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 taking place. The application was for the measurement of progesterone in human serum.

[0008] In the paper "Eur. J. Pharm. Biopharm. 2013, 85, 756-764" borosilicate vials are coated with a triethoxysilyl-modified dendritic polyglycerol-based polymer. After activating the surface with piranha solution and washing with water, an ethanolic 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] The document ES 2 799 351 describes an SPME device equipped with a metal-organic framework, specifically a CIM-80(AI) stationary phase, on a nickel / titanium support connected by APTES, which was used for the extraction and preconcentration of PAHs in water, improving the extraction yield of commercially available fibers.

[0010] Document WO 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 the volatile analytes present in the headspace are trapped in the coating by increasing the temperature, facilitating their transfer to the analysis device, which is a gas chromatograph coupled to a mass spectrometer.

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

[0012] Like any variation of click chemistry, the use of silane derivatives for surface functionalization is a well-known and widely used technique. Some of the most important publications in this regard are:

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

[0014] CN105694051 presents a polymer membrane prepared by crosslinking MOFs using a thiol-alkene-type click reaction. The membrane thus prepared can be used for the separation of substances.

[0015] Patent US 8,148,287 presents a method for attaching catalysts to siliceous mesocellular foam surfaces via an azide-alkyne click reaction.

[0016] In their paper "Anal.Chim.Acta 2019, 1060, 103-113," they propose the functionalization of flat glass supports for immobilizing oligonucleotides and proteins via thiol-based epoxide cleavage reactions and alkene-thiol reactions, under the name of click chemistry.

[0017] In their paper "Polymer 2014, 3330-3338" they show how to functionalize silicon wafers and glass slides with ionic liquid polymers through alkene-thiol and alkyne-azide reactions.

[0018] The article "Anal. Chem. 2007, 79, 1661-1667" also proposes the functionalization of glass slides with 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 new sorbents and stationary phases for extraction and chromatography. Click chemistry-type reactions have been applied to MOFs mainly to perform post-synthetic modifications or to functionalize MOFs with polymers or biomolecules. Summary of the Invention

[0020] The present invention relates to a device formed by a glass vessel, the inner wall of which is modified after successive activation, silanization and amidation reactions to house a porous crystalline coating, said coating having an atomic sequence -Si-ORM-MOF, covalently bonded in an inverse radial manner to the inner wall of the vessel, where R is an intermediate compound as defined below and M is a metal depending on the metal-organic framework (MOF).

[0021] There are four different possible methods for immobilizing the MOFs on the container, all based on the functionalization of covalently bound silanols on the glass surface.

[0022] This invention represents the first use of silane derivatives and click chemistry for the functionalization of glass surfaces enabling the immobilization of metal-organic frameworks.

[0023] This variety of anchors is implemented as a result of the following intermediate compounds:

[0024] [ka]

[0025] M can be any of the metals Zr, Ti, Al, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mg, Ca, Sc, Sr, depending on the type of MOF in the coating. The MOF can be any of those described below, preferably 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(AI), PCN-250(Fe2Co), PCN-250(Fe), UiO-67, HKUST-1, DUT-52, DUT-67, and modifications thereof with terminal amino or azide groups. Furthermore, other MOFs named in this way are not excluded, since experimental results show that the proposed invention works regardless of the MOF selected and is generally applicable.

[0026] The basis of the methodology of the present invention is the use of click chemistry to covalently attach MOFs to glass surfaces. In that sense, the present invention begins with APTES (3-aminopropyltriethoxysilane) attached to the glass surface, followed by carboxyl functionalization with terephthaloyl chloride to form an amide, to arrive at an intermediate compound (A), which then grows the MOF (Figure 2).

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

[0028] The intermediate compound (C) is generated from an epoxide cleavage click reaction using GLYMO (3-glycidyloxypropyltrimethoxysilane) and a MOF post-synthetically modified with 4-aminoethylbenzoic acid (Figure 4).

[0029] The intermediate compound (D) is obtained after a thiol-alkene click reaction using a MOF post-synthetically modified with 3-mercaptopropyltriethoxysilane and 4-vinylbenzoic acid.

[0030] The manufacturing method of the present invention covalently bonds the metal-organic framework (the adsorbent) to the glass substrate, preventing it from peeling off or deteriorating with use. The surface modification is done in a reverse radial manner, starting with the glass of the container and adding material to the interior of the container.

[0031] Glass vials are used as TFME devices for sample preparation for the qualitative or quantitative analysis of trace elements in samples of environmental, biological, etc. The containers allow the extraction and pre-concentration of the analytes of interest in the sample (water, urine, saliva, etc.), the subsequent analysis of which is carried out either by liquid chromatography (after liquid desorption with a suitable solvent compatible with the measuring instrument) or gas chromatography (by thermal desorption).

[0032] Using the device of the present invention, the sample handling process is much simpler than any of the current methods, as the vessel collects, extracts, and pre-concentrates the sample in one step, desorbs the analytes very easily, and is highly compatible with conventional laboratory analytical equipment. The device can be fabricated using any MOF, and therefore can be selected as needed depending on the particular application to which the vessel is dedicated.

[0033] There are no commercially available devices similar to the one presented here, but the most similar devices for sample preconcentration and pretreatment are based on solid phase microextraction (SPME) or thin film microextraction (TFME). Comparing the present invention with these devices can be misleading, since their usage is quite different. In commercially available 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 chromatographic method or injected directly into the gas chromatograph. 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 has advantages over other conventional devices since the sample and desorption solvent can be added in the same vessel without the need for complex intermediate steps.

[0035] Additionally, alternative uses of the present invention are proposed for administering medicines or for colouring and flavouring beverages.

[0036] Drug administration: A container coated on the inside with an adsorbent could be used to store the substance and return it to the medium in a specific dose. In that sense, the porous material could be loaded with the drug by adsorption of an ethanol solution. By pouring water into an empty container, but one that already contains the drug on its walls, desorption of the drug is initiated at a specific rate for the drug / MOF combination, allowing a relatively simple and visually acceptable administration, even in the case of drug rejection.

[0037] (coloring or flavoring beverages) Following the same method as for the administration of drugs, the container allows the metal-organic framework to be loaded with coloring or flavoring molecules, in that sense, during the serving of the beverage and when the container is filled with the beverage, desorption of the molecules trapped in the porous material occurs, 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 invention. The examples given below are merely illustrative and are not intended to be limiting of the invention. [Brief description of the drawings]

[0039] [Figure 1] Overall view of the device: I = screw cap, II = uncoated headspace, III = MOF-coated inner wall. [Diagram 2]A representative diagram of the chemical reactions of the first and last embodiments of the present invention is shown: step 1: surface activation, step 2: silanization reaction with terminal amino groups, step 3: reaction to form amides and expose terminal carboxyl groups, step 4: solvothermal MOF growth. [Diagram 3] A representative diagram of the second embodiment of the present invention is shown, which consists of step 1: surface activation, step 2: silanization reaction with terminal amino groups, step 3: reaction to form amides to expose terminal alkyne groups on the surface, and step 4: alkyne-azide click reaction using MOFs with terminal azide groups. [Figure 4] FIG. 1 shows a representative diagram of a third embodiment of the present invention: step 1: surface activation, step 2: silanization reaction with terminal epoxide groups, step 3: epoxide cleavage reaction using MOFs with terminal amino groups. [Diagram 5] FIG. 1 shows a scanning electron microscope (SEM) image of a cross-section of a glass container coated with MOF MIL-101(Fe). [Figure 6] Figure 2 shows the extraction efficiency of MOF MIL-101(FE) coated devices fabricated according to the first embodiment of the present invention 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] Figure 1 shows the extraction efficiency of MOF UiO-66(zr) coated devices 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), fabricated according to the method described in the fourth embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0040] However, some illustrative examples are given below that are not intended to limit the present invention.

[0041] In a first embodiment of the present invention, a stationary phase with an inverted radial atomic arrangement, container-Si-O-Si-(CH2)3-NH-C(=O)-(CH4)-COO-Fe-MOF, is obtained by four main steps, namely (1) activation of the silica surface by alkaline solution, (2) silanization reaction to generate terminal 3-aminopropyl groups, (3) amidation reaction to generate terminal carboxyl groups, and (4) growth of the MOF MIL-101(Fe) by solvothermal synthesis (Figure 2).

[0042] The process, carried out in a glass vessel, is as follows.

[0043] 1. Activation of the vessel is performed by adding 1M aqueous NaOH solution at 25° C. for 24 hours and after appropriate washing with water, a second 1M HCl solution is added for 30 minutes at 25° C.

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

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

[0046] 4. Finally, a solution of 0.1 M iron(III) chloride and 0.05 M terephthalic acid in dimethylformamide is added to the vessel to incorporate the MOF MIL-101(Fe). The vessel is closed and kept at 110 °C for 20 h until the MOF grows on the inner surface of the vessel.

[0047] The vessels thus produced have a uniform MOF layer of about 5 μm on the inner surface of the vessel (Figure 5). Before starting to use the vessel, it is convenient to wash it with dimethylformamide and ethanol / acetone and to heat the open vessel at low pressure to remove any DMF residues or reagents trapped in the pores of the material.

[0048] In a second embodiment of the present invention, a stationary phase with an inverted radial atomic arrangement, container-Si-O-Si-(CH2)3-NH-C(=O)-(CH2)2-(CN3H)-(CH2)3-(CH4)-COO-Zr-MOF, is obtained by four steps: (1) activation of the silica surface with an alkaline solution, (2) silanization reaction to generate terminal 3-aminopropyl groups, (3) amidation reaction to generate terminal alkyne groups, (4) post-synthetic modification of MOFs to incorporate terminal azide groups and alkyne-azide cycloaddition reaction to immobilize the MOFs (Figure 3).

[0049] The procedure, carried out in a glass vessel, is as follows.

[0050] 1. Activation of the vessel is performed by adding 1M aqueous NaOH solution at 25° C. for 24 hours and after appropriate washing with water a second 1M HCl solution is added at 25° C. for 30 minutes.

[0051] 2. The container glass is silanized by adding 3-aminopropyltriethoxysilane (APTES) and leaving it to act at 60°C for 24 hours.

[0052] 3. The amidation reaction to generate the terminal alkyne group 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-pentynoic acid (0.071 M) to the vessel. The vessel is closed and kept at 25° C. for 24 hours until the reaction is complete.

[0053] 4. Post-synthetic modification of the MOF UiO-66 is performed by immersion in a DMF solution containing 4-azidopropylbenzoic acid for 24 h.

[0054] 5. The alkyne-azide cycloaddition reaction is carried out by adding an aqueous solution of CuSO4·5H2O (0.06 M) and sodium ascorbate (0.12 M), followed by a dispersion of the MOF UiO-66 in water and acetonitrile (50:50, v / v). The vessel is closed and the reaction is left at 25 °C for 24 h.

[0055] The container thus produced has a uniform MOF layer of about 0.5 μm on the inner surface of the container. Before starting to use the container, it is convenient to wash it with ethanol / acetone and heat the open container under reduced pressure to remove any solvent residues or reagents that may remain trapped within the pores of the MOF.

[0056] In a third embodiment of the present invention (FIG. 4), a stationary phase with an inverted radial atomic arrangement, container-Si-O-Si-(CH2)3-O-CH2-CH(-OH)-CH2-NH-(CH2)2-(CH4)-COO-Zr-MOF, is obtained by three steps: (1) activation of the silica surface with an alkaline solution, (2) silanization reaction to generate terminal 3-glycidyloxypropyl groups, (3) post-synthetic modification of MOFs for surface functionalization with terminal amino groups and ring-opening reaction of the epoxide groups to immobilize the MOFs.

[0057] The procedure, carried out in a glass vessel, is as follows.

[0058] 1. Activation of the vessel is performed by adding 1M aqueous NaOH solution at 25° C. for 24 hours and after appropriate washing with water a second 1M HCl solution is added at 25° C. for 30 minutes.

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

[0060] 3. Post-synthetic modification of the MOF is performed by immersing the MOF in a DMF solution containing 4-aminopropylbenzoic acid for 24 hours.

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

[0062] The container thus produced has a uniform MOF layer of about 0.5 μm on the inner surface of the container. Before starting to use the container, it is convenient to wash it with ethanol / acetone and heat the open container under reduced pressure to remove any solvent residues or reagents that may remain trapped in the pores of the MOF.

[0063] In the final embodiment of the present invention (FIG. 2), a stationary phase with 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 alkaline solution, (2) silanization reaction to generate terminal 3-aminopropyl groups, (3) amidation reaction to generate terminal carboxyl groups, and (4) growth of MOF UiO-66(Zr) by solvothermal synthesis. The process, carried out in a glass container, is as follows:

[0064] 1. Activation of the vessel is performed by adding a 1M aqueous NaOH solution at 25° C. for 24 hours and, after appropriate washing with water, by adding a second 1M HCl solution at 25° C. for 30 minutes.

[0065] 2. The container glass is silanized by adding 3-aminopropylsilane (APTES) and leaving it to act at 60° C. for 24 hours.

[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 the vessel, followed by another 0.04M solution of terephthaloyl chloride in THF. The vessel is closed and kept at 60°C for 24 hours until the reaction is complete.

[0067] 4. Finally, a solution of 0.02 M zirconium(IV) chloride and 0.02 M terephthalic acid in dimethylformamide is added to the vessel to incorporate the MOF UiO-66(Zr). The vessel is closed and kept at 120 °C for 24 h until the MOF grows on the inner surface of the vessel.

[0068] The vessels thus prepared have a uniform MOF layer of about 1 μm on the inner surface of the vessel. Before starting to use the vessel, it is convenient to wash it with dimethylformamide and ethanol / acetone and to heat the open vessel at low pressure to remove any DMF residues or reagents that remain trapped in the pores of the material.

[0069] Figures 6 and 7 show the results obtained for the extraction efficiency of the analytical determination of eight organic compounds of different nature (PAHs, phenols, drugs, disinfectants, and solar panels) at a concentration of 10 ppb in 10 mL of water using the device of the first and last embodiment of the present invention. The process is very simple: add the sample to a vial, use an extraction time with stirring for 5 minutes, discard the supernatant after extraction, add 500 μL of acetonitrile to the vial, and perform a desorption step under vortex stirring for 5 minutes. No centrifugation is required during the entire microextraction method, ensuring the simplicity of the device in daily use.

Claims

1. A glass vessel having an inverse radially covalently bonded coating on its inner wall of the formula -Si-O-R-M-MOF, where 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-, n can have a value from 0 to 6, and M is a metal depending on the type of metal-organic framework (MOF).

2. 2. The glass container of 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 MOFs are 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 3. The glass container according to claim 2, wherein the glass container is selected from the group consisting of PCN-250(Fe), UiO-67, HKUST-1, DUT-52, DUT-67, or modified versions thereof having a terminal amino group or azide group.

4. 4. A method for producing a container according to claim 1, wherein the inner surface of the glass is chemically modified after successive activation, silanization and amidation reactions, and / or click chemistry reactions.

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

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

7. 4. Use of a container according to any one of claims 1 to 3 for colouring and flavouring beverages.

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