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    • 专利摘要:
    The present invention relates in particular to a method for detecting and measuring traces of H2S in a liquid sample, said method comprising the following steps: a) contacting a liquid sample to be analyzed with a porous hybrid solid of the MOF type ( "Metal Organic Framework") having -N3 groups on its outer surface or in its pores; b) subjecting the porous hybrid MOF type to laser irradiation or LED wavelength 300-400 nm, preferably 343 nm; the hybrid porous solid of the MOF type being previously isolated from the liquid sample and disposed on a two-dimensional support, or being suspended in the liquid sample inside a transparent-ultraviolet-walled container adapted to contain liquids; c) measuring the intensity of the photoluminescence signal emitted by the solid disposed on the support or in the container in the spectral zone 500-600 nm; and d) determining the concentration of H2S present in the sample from the photoluminescence signal thus measured using a previously established calibration curve. The present invention also relates to a device for detecting and measuring traces of H2S in a liquid sample. The present invention also relates to the use of a laser or LED for the detection or measurement of traces of H2S in a liquid sample, as well as the use of a porous hybrid solid of the MOF type ("Metal Organic Framework" ) having -N3 groups on its outer surface or in its pores, for the same purpose.
    公开号:FR3034200A1
    申请号:FR1552769
    申请日:2015-03-31
    公开日:2016-09-30
    发明作者:Jerome Canivet；Alexandre Legrand；Elsje Quadrelli；David Farrusseng；Volodymyr Lysenko
    申请人:Centre National de la Recherche Scientifique CNRS；Universite Claude Bernard Lyon 1 UCBL；Ecole Superieure de Chimie Physique Electronique de Lyon；
    IPC主号:
    专利说明:

    [0001] This patent application claims the priority of the provisional French patent application No. 15/52431 filed on March 24, 2015. DESCRIPTION TECHNICAL FIELD The present invention relates in particular to: a method for detecting and measuring traces of H2S in a liquid sample. The present invention also relates to a device for detecting and measuring traces of H2S in a liquid sample, allowing the implementation of said method. The present invention also relates to the use of a laser or LED for the detection or measurement of traces of H2S in a liquid sample, as well as the use of a porous hybrid solid of the MOF type ("Metal Organic Framework" ) having -N3 groups on its outer surface or in its pores for the same purpose. In the description below, references in brackets [] refer to the list of references at the end of the text. State of the art Four major noncommunicable diseases "NCDs" (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes) account for 82% of deaths from NCDs worldwide, representing 31 million deaths per year. For example, cardiovascular disease was the leading cause of death of NCDs in 2012 and was responsible for 17.5 million deaths, or 46% of deaths attributed to NCDs.
    [0002] 3034200 2 Nearly 36 million people have Alzheimer's disease or a related condition worldwide, but only one in four people have been diagnosed. Endogenous H2S has recently been revealed as a biomarker in a number of diseases, including Alzheimer's disease, cancer, Down's syndrome, diabetes, chronic obstructive pulmonary disease (COPD) and chronic obstructive pulmonary disease (COPD). In English) or cardiovascular diseases. Its physiological concentration, that is to say in a healthy individual, is only a few nanomoles (nmol) per liter of blood. However, for some diseases (e.g., Alzheimer's, cancer, hypertension, etc.), the concentration of H25 increases in the blood or target organs before the onset of symptoms of the disease. Typically, the concentration increases from a few nmol / L to a few pmol / L and in a sick subject, the concentration of H25 can vary from nanomolar to 100 pmol / L.
    [0003] Early detection of a sudden increase or decrease in the concentration of H25 in the blood would allow early diagnosis of a risk of developing these diseases. However, the existing techniques for measuring the concentration of H25 are not suitable. For example, the tools / techniques for measuring H25 in air do not make it possible to measure the H25 content in liquid samples, such as physiological liquids (blood, serum, etc.) because of their possible instability and possible interactions with other components of the fluids in question (eg, water, other sulfur products, phosphates, etc.). With regard to H25 in solution, the current R & D analysis devices are based on the UV-Vis spectral response of a photoluminescent molecule or material exposed to H25 and subjected to UV irradiation, and are themselves also inadequate and unsuitable for solving the technical problem. For example, polyaromatic compounds - particularly structurally sophisticated organic chromophores - carrying azide functions have been developed for the detection of H25 in solution. [1], [2] However, this approach suffers from severe technical limitations among which are: 3034200 3 - In contact with the aqueous liquid sample, the molecules are not soluble, resulting in technical difficulties of handling and measurement; Most of the compounds reported relate to an in vivo application in medical imaging, leading to considerations of toxicity and applicability to humans. Another method relies on the detection of H2S using a nanoporous material functionalized with azides, but here again the technique is not adapted to the problem raised because its limit of detection (> 100 μM) is indeed 10 to relevant concentrations of physiological / pathological H2S. [3] In fact, the endogenous physiological (healthy subject) and pathological (Alzheimer's disease-type) endogenous H2S concentrations are below the threshold of 100 pmol / L (of the order of nanomolar to 100 micromolar). [4] Thus, there is currently no method or portable medical test device 15 ("point-of-care testing" (POCT) or "bed-side testing" in English) on the market to measure the concentration of H2S in the blood or other biological fluid, and make it possible to perform simple tests (such as a blood or urine test (urine strip test)) on the treatment site of a patient (at the bedside). its bed for example) to easily and quickly determine the H2S content in a patient sample. There is therefore a real need for improved methods and devices for detecting and measuring H 2 S traces in a liquid sample, particularly biological source samples, especially for diagnostic purposes. DISCLOSURE OF THE INVENTION The present invention is specifically intended to meet these needs and disadvantages of the prior art by providing a method for detecting and measuring traces of H2S in a liquid sample, said method comprising the following steps: : A) contacting a liquid sample to be analyzed with a porous hybrid solid of the MOF ("Metal Organic Framework") type having -N3 groups on its external surface or in its pores; b) subjecting the porous MOF-type hybrid solid to laser irradiation or LED of wavelength 300-400 nm, preferably 343 nm; the hybrid porous solid of the MOF type being previously isolated from the liquid sample and disposed on a two-dimensional support, or being suspended in the liquid sample inside a transparent-ultraviolet-walled container adapted to contain liquids; C) measuring the intensity of the photoluminescence signal emitted by the solid disposed on the support or in the container in the spectral zone 500-600 nm; and d) determining the concentration of H2S present in the sample from the photoluminescence signal thus measured using a previously established calibration curve. As used herein, the term "MOF type porous hybrid solid" may be used interchangeably with the abbreviation "MOF" or "MOF solid". By "H2S traces" is meant a concentration [H2S] <100 pmol / L, preferably between 1 nmol / L and 100 pmol / L. The basic principle is that MOF functionalized with MOF-N3 azides has no usable luminescence signal at a given wavelength (detection wavelength). This reacts with the H2S present in the liquid sample to be analyzed to give an MOF containing both -N3 and -NH2 groups (the MOF solid being advantageously used in excess with respect to the low content of H2S to be measured. ). Advantageously, the amount of -NH 2 groups at the surface and in the pores of the MOF, after contacting with the liquid sample, corresponds stoichiometrically to the amount of H2S present in the liquid sample. MOF-NH2 has a luminescence signal at a determined detection wavelength. The intensity of this signal increases with the growth of the amount of -NH 2 present at the surface and in the pores of the MOF, and thus makes it possible to quantify the traces of H2S present in a liquid sample.
    [0004] The present invention thus lays down the principle of the use of a functionalized metal-organic framework (MOF) solid (-N3), in combination with an adequate light source, which "responds" to the concentration of H2S ( sensor) in a given liquid sample by emission of a specific wave under UV irradiation (in this case photoluminescence). Advantageously, the contacting step a) is carried out for a time sufficient to allow the reaction of the H2S traces present in the liquid sample with the -N3 groups of the MOF solid leading to the formation of -NH2 functions. The reaction time required for this chemical transformation is small, of the order of one minute. Thus, the step a) of contacting can be carried out for 1 to 10 minutes, 1 to 5 minutes, preferably 2 minutes. Advantageously, the calibration curve used in step d) can be established according to a method comprising the following steps: a1) contacting a liquid sample containing a given concentration of S2-, with a quantity M of porous hybrid solid of MOF ("Metal Organic Framework") type having -N3 groups on its outer surface or in its pores; 131) subjecting the hybrid porous solid of the MOF type to laser irradiation of wavelength 300-400 nm, preferably 343 nm; the hybrid porous solid of the MOF type being previously isolated from the liquid sample and disposed on a two-dimensional support, or being suspended in the liquid sample inside a transparent-ultraviolet-walled container adapted to contain liquids; C) measuring the intensity of the photoluminescence signal emitted in the 500-600 nm spectral region; dl) repeat steps a1 to c1) with a series of at least 4 different [SI concentrations between 0.01 μM and 1000 μM, preferably 2 to 400 μM; (E1) draw up the calibration curve from the values of the integral intensity corresponding to the area under the photoluminescence spectrum measured between 500 and 600 nm, showing on the abscissa the concentration of Na2S and on the ordinate the value of integral intensity of photoluminescence.
    [0005] Advantageously, the quantity M of MOF is sufficient to make it possible to establish a calibration curve for the given MOF. The MOF may be used in excess of the expected level of H2S concentration in the liquid sample to be analyzed. For example, if it is a sample from a biological source (expected concentration order - 1 nanomolar to 100 micromolar) the amount of MOF-N3 used will be such that the N3 functions will be in excess of to the H2S contained in the sample to be analyzed, to ensure the complete reaction of the H2S present (possibly in the form of S2-) with the azide functions present on the MOF. For example, a quantity of 0.1 to 50 mg of MOF-N3 may be used for 0.1 to 10 ml of liquid sample, for example 1 to 15 mg of MOF-N3 may be used for 0.5 to 2 ml of sample liquid or 10 mg of MOF-N3 may be used for 0.8 mL of liquid sample. Advantageously, the same amount of MOF-N3 can be used for each calibration point used to establish the calibration curve. Advantageously, the contacting step a1) is carried out for a time sufficient to allow the reaction of the S 2 - ions present in the liquid sample with the groups -N 3 of the MOF solid leading to the formation of -NH 2 functions. The reaction time required for this chemical conversion is small, on the order of a minute. Thus, the step a) of contacting can be carried out for 1 to 10 minutes, 1 to 5 minutes, preferably 2 minutes. Advantageously, the S2 - ions present in the liquid sample to be analyzed can come from Na2S or H2S. In fact, hydrogen sulfide (H2S) being a dissolved gas, its handling in organic or aqueous solvents at standard temperature and pressure, in particular its sampling by means of a syringe in a commercial concentrated stock solution or prepared after saturation of the solvent with H2S gas above 0.1 mole per liter, causes a decrease in its solution concentration by its vaporization. To circumvent this problem, sodium sulfide (Na2S) can be used in replacement of hydrogen sulfide. Na2S is a more easily manipulated solid and the preparation of low concentration solutions is done by simply weighing the solid and then by simply diluting a concentrated stock solution. This technique facilitates the establishment of calibration curves for the implementation of the present invention.
    [0006] Advantageously, the calibration curve can be established with a sufficient number of calibration points to establish a reliable calibration. A minimum of four calibration points can be advantageously used, even 5, 6, 7, 8, 9, 10 or more. Each calibration point is associated with a particular concentration [S2-]. For better reliability, each calibration point can be established from several measurement points of the same concentration [S2], for example 2, 3, 4 or more measuring points. Each calibration point may be the average of the points measured for each particular concentration [S2-]. In the same way, for better reliability, advantageously the calibration curve can be drawn from a series of concentrations [S2-] (at least four different), spaced over a concentration range [S2] covering 0.01 pM at 1000 μM, or even 0.01 μM at 400 μM, more preferably 0.01 μM at 300 μM, more preferably 0.01 μM at 200 μM, still more preferably 0.01 μM at 100 μM.
    [0007] Advantageously, the liquid sample of steps a) and al) (containing dissolved H25 or in which Na2S has been dissolved) may be a solution composed of a polar solvent such as dimethyl sulfoxide, dimethylformamide, an alcohol, water or a mixture of at least two of them in all proportions. It may be for example an aqueous solution containing 20 H 25 and / or S 2 - ions, which may additionally contain one or more alkali metal salts in solution, preferably sodium or potassium salts such as chloride sodium chloride, potassium chloride, sodium phosphate and potassium phosphate. The liquid sample may optionally also contain amino acid residues such as cysteine. The liquid sample may also consist of a solvent derived from a biological medium such as serum. The liquid sample may also be from a biological sample, which may be conditioned (by solvent addition or dilution) or pre-treated, including preliminary separation techniques, for the purpose of analysis.
    [0008] By "biological sample" is meant, without limitation, cell cultures or extracts thereof; biopsy material from an animal (eg, mammal) or extracts thereof; and blood, saliva, urine, excrement, sperm, tears, or other bodily fluids or extracts from them. For example, the term "biological sample" refers to any solid or liquid sample obtained from, excreted by or secreted by a living organism, including unicellular microorganisms (such as bacteria and yeasts) and multicellular organisms (such as plants and animals, for example a vertebrate or a mammal, and in particular a healthy or apparently healthy human subject or a human patient suffering from a disease or disease to be diagnosed). The biological sample may be in any form, including a solid material, such as tissue, cells, cell pellet, cell extract, cell homogenates or cell fractions; or a biopsy, or a biological fluid. The biological fluid can be obtained from any source (e.g. blood, saliva (or a mouthwash containing oral cells), tears, plasma, serum, urine, bile, cerebrospinal fluid, amniotic fluid, peritoneal fluid, and pleural fluid, or cells derived therefrom, aqueous or vitreous, or any body secretion), a transudate, an exudate (e.g. fluid obtained from an abscess or any other site of infection or inflammation), or the fluid obtained from a joint (eg a normal joint or joint affected by diseases such as rheumatoid arthritis, osteoarthritis, gout or septic arthritis). The biological sample can be obtained from any organ or tissue (including a sample of a biopsy or autopsy) or can include cells (if the primary cells or cells in culture) or medium. conditioned by a cell, tissue or organ. For example, they may be fibroblast cells (eg connective tissue from the dermis), which can be tested by the method of the invention to evaluate / determine their production of H2S. The biological samples may also include sections of tissue such as frozen sections taken for histological purposes. The biological samples also include mixtures of biological molecules comprising proteins, lipids, carbohydrates and nucleic acids generated by partial or complete fractionation of cell or tissue homogenates. Although the sample is preferably taken from a human subject, the biological samples can come from any animal, plant, bacterium, virus, yeast, etc. The term "animal" as used herein refers to humans as well as non-human animals, in any stage of development, including, for example, mammals, birds, reptiles, amphibians, fish, worms and individual cells. . Cell cultures and living tissue samples are considered to be pluralities of animals. For example, the "non-human" animal may be a mammal (eg, a rodent, mouse, rat, rabbit, monkey, dog, cat, sheep, cattle, primate, or pig ). If desired, the biological sample may be pretreated, including preliminary separation techniques. In the present invention, the MOF used can be any MOF solid bearing azide groups (-N3) on its outer surface or in its pores, whatever its method of production. Such solids, as well as methods for their synthesis, are described for example in the following patent documents: FR2958945, WO 2011/48283 (FR2951723), WO 2011/48280 (FR2951725), WO 2011/33185 (FR2950347) and WO 2011 / 48282 (FR2951724). [5-9] The MOF solid according to the invention may comprise di-, tri- or tetravalent metal atoms. The metal atoms can have an octahedral, pentahedral, tetrahedral geometry, or even be in higher coordination in the structure of the material. For example, it may be a metal ion based MOF selected from the group consisting of Fe2 +, Fe3 +, Zn2 +, Zr4 +, Ti4 +, Ca2 +, Mg2 +, In3 +, Cr3 + and Al3 +; preferably Fe2 +, Fe3 +, Zn2 +, Zr4 +, In3 + and Al3 +, more preferably In3 +, Zr4 +, and Al3 +. Advantageously, it may be an MOF of which at least one ligand comprises an aromatic group carrying an azide (N 3) function. Advantageously, it may be an aromatic di-, tri-, tetra- or hexa-carboxylate ligand bearing an azide (N 3) function. For example, the ligand may be selected from the group consisting of: (RI-3) t (RI-3) t -O2C CO2 -02C 3034200 CO2 -02C it C (R) t 02C / C --- - (RL3) t CO2-CO2- -02C0O2 (RL3) t -1 = N t (RI-3) / 02C ) CO2-N / - / ----- (RL3) ## STR1 ## wherein R 1 - (R 1 - 3) t CO 2 --O 2 --CH 2 - (R 1 - 3) t (RI-3) t co2-c02-c02-c02- (RL3) t .........---, '<-> -... ,, (R1-3) t c02-c02 CO2 (RL3) t (RL3) t CO2 (RL3) t (RL3) t CO2 (RL3) t (RL3) t - CO2 (RL3) t (RL3) t 1 02C / NK-CO2- / -02C CO2- (RI-3) 1 / NII 7 (- (R1-3) t 0C2 CO2- A A1 1 (R'-3) t (RL3) t A where A 1, A 2 and A 3 independently represent (R 1 -3) t 1 / CO 2 - wherein: each occurrence of t independently represents an integer of 1 to 4 as a function of the valence of the aromatic radical, and each occurrence of RL 3 is independently H, halogen (preferably F, Cl or Br), OH, N3, NH2, NO2 or C1-C6 alkyl (preferably methyl or ethyl); ns an occurrence of RL3 represents N3.
    [0009] Advantageously, the MOF solid contains at least one azotureterephthalate ligand of the following formula: ## STR2 ## in which t represents an integer of from 1 to 4, preferably 1.
    [0010] Advantageously, the MOF solid contains at least one azide-biphenyl-dicarboxylate ligand of the following formula: ## STR2 ## in which t 1 and t 2 independently represent an integer of 0 to 4 provided that t 1 and t 2 are not both equal at 0, preferably t1 and / or t2 is (nt) 1, more preferably t1 or t2 is 1. For example, the MOF solid may contain at least one azide-biphenyl-dicarboxylate ligand of the following formula: ## STR2 ## By "coordination" or "coordination number" is meant the number of bonds for which the two electrons shared in the bond originate from the same atom. The electron donor atom acquires a positive charge while the electron acceptor atom acquires a negative charge. In addition, the MOF solid according to the invention can be in various forms or "phases" in view of the various possibilities of organization and connections of the ligands to the metal or to the metal group.
    [0011] For the purposes of the present invention, the term "phase" is intended to mean a hybrid composition comprising at least one metal and at least one organic ligand having a defined crystalline structure. Advantageously, the ligand L of the unit of formula (I) MOF solids of the present invention may be a ligand carrying several complexing functions including carboxylates, phosphonates, sulfonate, imidazolates, preferably the carboxylate group is a di-, tri- , tetra- or hexa-carboxylate. The term "solid" in the sense of the present invention any type of crystalline material. Said solid may for example be in the form of crystals, powder, particles of various shapes, for example spherical, cubic, parallelepipedic, rhombohedral, lamellar, etc. The particles may be in the form of nanoparticles. By "nanoparticle" is meant a particle of size less than 1 micron. In particular, the MOF solid nanoparticles according to the invention may have a diameter of less than 1000 nanometers, preferably less than 500 nm, more preferably less than 250 nm, and more particularly less than 100 nm. In general, the term "substituted", preceded or not by the term "optionally", and the substituents described in the formulas of the present application, denote the replacement of a hydrogen radical in a given structure with the radical of a radical. specified substitute. The term "substituted" refers for example to the replacement of a hydrogen radical in a given structure by a radical designated "substituent". When more than one position may be substituted, the substituents may be the same or different at each position.
    [0012] For the purposes of the present invention, the term "ligand" means a ligand (including, for example, neutral species and ions) coordinated with at least two metal sites of the MOF, participating in the distance between these metal sites and the formation empty spaces or pores. The ligand can comprise several complexing functions comprising carboxylates, phosphonates, sulphonates, imidazolates, preferably from 2 to 6 functional groups which can be mono, bi tri or tetradentates, ie comprise 1, 2, 3 or 4 d attachment to the metal site.
    [0013] For the purposes of the present invention, the term "alkyl" means a linear, branched or cyclic, saturated or unsaturated, optionally substituted carbon radical comprising 1 to 25 carbon atoms, for example 1 to 10 carbon atoms, for example 1 to 8 carbon atoms, for example 1 to 6 carbon atoms.
    [0014] Advantageously, the MOF used in the context of the present invention can be obtained by any method known to those skilled in the art. In particular, the MOF can be obtained according to one of the following three strategies: A) Process for the preparation by self-assembly of hybrid porous solid type MOF from at least one ligand carrying an azide group (-N 3) B) Process for the post-synthetic chemical transformation of the NH 2 functions of a hybrid porous solid type MOF-NH 2 in the azide group (-N 3) -C) Process for post-synthetic functionalization of a hybrid porous solid type MOF with an azide group (- N3) by ligand exchange.
    [0015] By way of example, process A) may be carried out according to any known method for preparing MOF in which at least one azide terephthalate ligand of formula: -O WC CO2- in which t represents an integer of 1 to 4, preferably 1; is used in the self-assembly process. In another example, the process A) can be carried out according to any known method for preparing MOF in which at least one azide-biphenyl-dicarboxylate ligand of formula: ## STR2 ## in which t1 and t2 independently represent an integer from 0 to 4 with the proviso that t1 and t2 are not both 0, preferably t1 and / or t2 is 1, more preferably t1 or t2 is 1; is used in the self-assembly process, especially the following ligand N3 002-. For example, it may be a variation of the method published by Goto et al. in Journal of the American Chemical Society 2008, 130, 14354 [10] according to which a metal salt such as indium nitrate, zinc nitrate, iron chloride, zirconium chloride or aluminum chloride is reacted 2-azide-terephthalic acid in a polar solvent such as dimethyl formamide, an alcohol or water at a suitable temperature (generally between 50 and 150 ° C) for a period suitable for carrying out the reaction ( for example 18 to 72 hours). The isolated solid after filtration can then be washed with a suitable solvent or solvent mixture (for example the synthesis solvent, then dichloromethane) and dried under primary vacuum at room temperature. The process B) can be carried out according to the method described in the patent documents WO 2011/48283 (FR2951723) [6] and the patent application FR2958945 15 [5] from any MOF carrying, on at least its ligands, NH2 groups capable of being chemically transformed into N3 group. For example, it may be the following MOFs: Al / Cr / Fe-MIL-101-NH2, In / Al-MIL-68-NH2, Al / Fe-MIL53-NH2, DMOF-1-NH2, 1, CAU-10-NH 2, Zr-UiO-66-NH 2, or UMCM-1-NH 2. MOF is reacted with trimethylsilyl azide and tert-butyl nitrite in a suitable polar solvent (eg, tetrahydrofuran). The reaction can be carried out at room temperature for 12 hours. The isolated solid after filtration is then washed with a solvent, or mixture of solvents, suitable (for example it may be the synthetic solvent (eg tetrahydrofuran) and then dichloromethane) and dried under primary vacuum at room temperature . The chemical formulas of these compounds are: Al / Cr / Fe-MIL-101-NH2 = Fe30X [C6H3 (CO2) 2-NH2] 3, Al30X [C6H3 (CO2) 2 -N1-12] 3, Cr3OX [C6H3 ( CO2) 2-NH2] 3, wherein X is F, Cl or OH In / AI-MIL-68-NH2 = InOH [C6H3 (CO2) 2 -NH2], AlOH [C6H3 (CO2) Z-NH2] -02C 3034200 16 Al / Fe-MIL-53-NH2 = AlOH [C6H3 (CO2) 2 -NH2], FeOH [C6H3 (CO2) 2-N1-12] DM0E-1-NH2 = Zn2 (C6H12N2) [C61-13 ( CO2) 2-N1-12] 2 CAU-1 = A14 (OH) 2 (OCH3) 4 [C6H3 (CO2) 2-N1-12] 3 CAU-10-NH2 = [Al (OH) (C8H304NH2)] 5 UiO-66-NH2 = Zr604 (OH) 4 [C61-13 (CO2) 2 -N1-12] 6 UMCM-1-NH2 = (Zn40) 3 [C6H3 (C6H4CO2) 3] 4 [C61-13 (CO2) 2-N1-12] 3 The properties of some of these MOFs are described, for example, in international applications WO 2009/77670 [11] and WO 2009/77671. [12] The synthesis and properties of the various MOFs referenced above are described in the following references: Fe-MIL-101-NH2, Al-MIL-53-NH2 and Fe-MIL-53-NH2: Inorganic Chemistry 2008, 47, 7568. [13] - Cr-MIL-101-NH2: Chemical Communications 2011, 47, 2838. [14] - Al-MIL-101-NH2: Microporous and Mesoporous Materials 2012, 164, 38. [ In-MIL-68-NH2: WO 2011/048284. [16] - Al-MIL-68-NH2: Journal of Material Chemistry 2012, 22, 10210. [17] - DMOF-1-NH2 and UMCM-1-NH2: Inorganic Chemistry 2009, 48, 296-306. [18] CAU-1: Angewandte Chemie - International Edition 2009, 48, 5163. [19] - Ui0-66-NH2: Chemistry of Materials 2010, 22, 6632-6640. [20] - CAU-10-NH 2: Chem. Mater., 2012, 25, 17-26 [23] Different MOF materials were developed at the Lavoisier Institute of Versailles with various phases, named "MIL" (for "Institut Lavoisier Material").
    [0016] The designation "MIL" of these structures is followed by an arbitrary number n given by the inventors to identify the different phases. In this document, the acronym "UiO" is an abbreviation of the English term "University of Oslo" (University of Oslo).
    [0017] In this document, the acronym "DMOF" is the abbreviation of the term "DABCO metal organic framework" in which the acronym DABCO stands for 1,4-diazabicyclo [2.2.2] octane. In this document, the acronym "CAU" is an abbreviation of the term "Christian 5 Albrechts University" (University Christian Michigan Albrechts) In this document, the abbreviation "UMCM" is an abbreviation of "University of Michigan Crystalline Material" (Crystalline material from the University of Michigan) Process C) can be performed according to the method published by Kim et al. in Chemical Science 2012, 3, 126 [21] according to which an MOF of which at least one of the ligands is a terephthalate, preferably In-MIL-68 or Zr-UiO-66 or Al-MIL53 or Al-MIL-101, is reacted with 2-azide-terephthalic acid in a polar solvent such as dimethylformamide, an alcohol or water at an adequate temperature (usually room temperature) for a period of time suitable for carrying out the reaction (e.g. 5 days). The isolated solid after filtration can then be washed with a solvent, or mixture of solvents, suitable (for example the synthesis solvent, then dichloromethane) and dried under primary vacuum at room temperature. The synthesis of MOF materials may preferably be carried out in the presence of energy which may be provided, for example, by heating, such as, for example, hydrothermal or solvothermal conditions, but also by microwaves, ultrasonics, grinding, process involving a supercritical fluid, etc. The corresponding protocols are those known to those skilled in the art. Nonlimiting examples of protocols that can be used for hydrothermal or solvothermal conditions are described, for example, in the international applications WO 2009/077670 and WO 2009/077671, and in the references cited therein for this purpose. [11, 12] Hydrothermal or solvothermal conditions, whose reaction temperatures may vary between 0 and 220 ° C, are generally carried out in glass (or plastic) containers when the temperature is below the boiling point. solvent. When the temperature is higher or when the reaction is carried out in the presence of fluorine, teflon bodies inserted into metal bombs are employed. The solvents used are generally polar. In particular, the following solvents may be used: water, alcohols, dimethylformamide, dimethylsulfoxide, acetonitrile, tetrahydrofuran, diethylformamide, chloroform, cyclohexane, acetone, cyanobenzene, dichloromethane, nitrobenzene ethylene glycol, dimethylacetamide or mixtures of these solvents. One or more co-solvents may also be added at any stage of the synthesis for better solubilization of the compounds of the mixture. These may include monocarboxylic acids, such as acetic acid, formic acid, benzoic acid, and the like. When the co-solvent is a monocarboxylic acid, the latter, in addition to a solubilizing effect, also makes it possible to stop the crystalline growth of the MOF solid.
    [0018] Indeed, the carboxylic function coordinates with the metal ion of the MOF, which will not be able to bind to another metal atom because of the absence of a second -COOH function on the co-solvent molecule. Thus, the growth of the crystal lattice is slowed down and stopped. The addition of a monocarboxylic cosolvent, such as acetic acid, formic acid, benzoic acid, etc., thus makes it possible to reduce the size of the MOF solid particles obtained. The use of a monocarboxylic co-solvent can therefore promote the production of nanoparticles (particles of size <1 μm). Unless otherwise indicated, the various embodiments described herein relating to MOF-N3 materials, and MOF materials in general, apply to both their uses and to their preparation process according to the present invention. Advantageously, the MOF-N3 used in the context of the present invention may be chosen from the MOFs Al / Cr / Fe-MIL-101-N3, In / Al-MIL-68-N3, Al / FeMIL-53-N3, DMOF-1-N3, CAU-1-N3, CAU-10-N3, Zr-U10-66-N3, or UMCM-1-N3; Advantageously the MOFs In-MIL-68-N3, Zr-U10-66-N3 or Al-MIL-101-N3; preferably Al-MIL-101-N3.
    [0019] Advantageously, the method according to the invention makes it possible to measure / quantify in vitro H 2 S concentrations in a range that is appropriate for pathological / physiological diagnostics. Advantageously, the traces of H2S present in the sample analyzed are between 0.01 μM and 1000 μM, preferably 2 to 400 μM. Advantageously, any laser source or LED capable of irradiating between 300-400 nm may be used in step b) or 131). The laser used in step b) or 131) may be a pulsed or continuous laser. For example, it may be a ytterbium femtosecond pulsed laser, such as the Mikan model (Amplitude systems), emitting the excitation wavelength of 343 nm at the average power of the order of 3 mW, with an excitation time <250 fs and a repetition frequency of 54 MHz. Alternatively, a continuous UV laser with a power of about 100W can be used. In step c) or cl), the photoluminescence signal emitted by the irradiated MOF solid can be advantageously detected at 500-600 nm, preferably at 580 nm. Advantageously, the photoluminescence measuring step c) or cl) can be carried out at a suitable temperature, for example at room temperature. Detection of the photoluminescence signal can be done using a conventional camera (CCD camera) in the form of imaging. For example, the spectral decomposition of the photoluminescence signal can be performed with a spectrometer (eg Horiba JobinYvon iHR-320) and can be detected by a CCD camera (eg Horiba Symphony 1024x256) cooled under nitrogen. In step c) or cl), the measurement of the photoluminescence signal can be carried out by integrating the signal detected by the usual methods. As a standard, the collected raw photoluminescence spectrum is typically corrected by an optical transfer function characteristic of the installation. This method is known to those skilled in the art. The integral photoluminescence signal is given by the value of the area under the photoluminescence spectrum collected between 500 and 600 nm. Particularly advantageously, the excitation by a laser allows a stronger signal intensity and a gain in sensitivity. In particular, the excitation at 300-400 nm (preferably 343 nm) allows the detection at 500-600 nm of a peak maximum (located towards 580 nm) characteristic for low concentrations, relevant for the concentrations of H2S endogenous physiological (healthy subject) and pathological (subject suffering from Alzheimer type disease) which are of the order of nanomolar to 100 micromolar [4]. Irradiation of a MOF-N3 with a conventional UV lamp allows the recovery of a signal with a maximum photoluminescence intensity at 400-500 nm. However, the peak at 400-500 nm does not allow a calibration of the amount of Na2S / H2S in solution for low concentrations, less than 100 micromolar. The reader will be able to refer on this point to the article of 2014 Sci Report 7053 [3] which reports the use of an MOF functionalised by azides (N3) to detect selectively Na2S at a concentration of 118 micromolar to 4 millimolar (UV lamp excitation at 334 nm and emission measurement at 436 nm), ie 2-3 orders of magnitude above the relevant concentrations for in vitro diagnostics. Unexpectedly, the inventors have discovered that irradiation using a UV or LED laser suppresses the maximum photoluminescence at 400-500 nm typically obtained with a conventional UV lamp for concentrations> 400 micromolar and appears a new maximum at 500-600 nm for concentrations <400 micromolar. This peak at 500-600 nm is characteristic of another type of electronic transition within the ligand of MOF-N3 and allows calibration for concentrations of 2 to 400 micromolar, and thus measurement / determination of H2S concentration. 100 micromolar. The electron transition observed with the peak at 500-600 nm is not visible with a conventional UV lamp.
    [0020] Advantageously, the two-dimensional support used in step b) or b1) can be any stable support for laser and LED irradiations, in particular in the range 300-400 nm. For example, it may be a silicon support. Advantageously, quantum dots may optionally be deposited on the two-dimensional support used in step b) or b1). Quantum dots have the characteristic that by adjusting the size and chemistry of the quantum dots, the optical properties of the material, such as light absorption or light emission, can be adapted to the desired characteristics. For example, the use of quantum dots may make it possible to increase the intensity of the MOF photoluminescence signal due to larger quantum dots absorption coefficients than MOFs and the transfer of excitation energy to the luminescent site of the MOFs. This can be particularly advantageous in the case where the light source used is a LED, which is of lower power than a laser (pulsed or continuous). The lower power of the LEDs relative to the laser would be offset by the increase in the signal due to the use of a two-dimensional support on which quantum dots are deposited. In the context of the present invention, the quantum dots may be metallic and / or semiconducting nanoparticles. Thus, the two-dimensional support used in step b) or b1 may for example be a silicon support, on which metallic and / or semiconducting nanoparticles are optionally deposited. Advantageously, among the semiconductor nanoparticles, it is possible to use SiC nanoparticles which are chemically, thermally and mechanically stable. The use of silicon nanoparticles (quantum dots) for photoluminescence imaging is known, and this technology can be adapted / applied in the context of the present invention. For example, reference may be made to the teaching of patent document WO 2010/43832 [22] on this point. Reference may be made in particular to Figure 6 of this document, and the parts of the text relating thereto. The SiC nanoparticles may be obtained by a method of etching an SiC substrate, the etching being obtained by electrochemical etching of the SiC substrate, advantageously a solid SiC substrate. "Solid SiC substrate" means any chemical compound consisting of silicon (Si) and carbon (C) atoms chemically bonded to one another and at least one of which is linear in size (height, width, length, diameter, etc.) is greater than 1 mm SiC nanoparticles can be obtained by a method of laser ablating an SiC substrate through a volume of water or another solvent, the SiC nanoparticles can be deposited on the two-dimensional support according to the present invention, by any method known for this purpose, for example dip-coating, or metal particles may also be used as a quantum dot. For example, silver and / or gold particles may be deposited on the two-dimensional support according to the present invention by any known method. 'at For example, an electrodepositon, chemical deposition such as "electroless deposition" in English or deposition dip-coating ("dip-coating" in English). Advantageously, the two-dimensional support used in step b) or 131) is coated with a thin layer of the MOF obtained at the end of step a) or a1), respectively (i.e. reaction of the azide groups present on the MOF with the H2S present in the sample to be analyzed (possibly in the form of S2-)). For example, after step a) or a1), the MOF solid can be isolated by centrifugation and dried under primary vacuum at room temperature. This solid 10 can then be spread in the form of a thin layer on the two-dimensional support (for example a silicon support), which can be placed in the optical photoluminescence measuring system for the implementation of step b or 131) . Advantageously, the transparent-walled container used in step b) or 131) may be a parallelepipedic or cylindrical quartz cuvette conventionally used in UV spectrometry. The present invention also relates to a device for detecting and measuring traces of H2S in a liquid sample, allowing the implementation of the method according to the invention, in all the variants described above. Advantageously, the device may comprise: i) a receptacle adapted to receive a two-dimensional support coated with a thin layer of a porous hybrid solid of the MOF ("Metal Organic Framework") type having -N3 groups at its external surface or in his pores; or a clear-walled vessel containing a liquid medium in which a porous hybrid MOF-type ("Metal Organic Framework") solid having -N3 groups on its outer surface or in its pores is suspended; Ii) a light source selected from a laser or LED, preferably a pulsed laser, for irradiation at 300-400 nm, preferably 343 nm; and iii) a detector adapted for detecting a photoluminescence signal at 500-600 nm.
    [0021] All the variants described above, in particular for the type of liquid sample, the MOF, the two-dimensional support, the transparent-walled container, the light source, the detection of the photoluminescence signal, and the establishment of a calibration curve, are mutadis mutandis applicable to said device. Advantageously, the device can be of small size, so that it is suitable for use in "portable" mode. In particular, the device is advantageously adapted for carrying out simple tests (such as a blood or urine test) on the treatment site of a patient (at the bedside of his bed for example) to determine easily and quickly the H2S content. in a patient sample ("point-of-care testing" (POCT) or "bed-side testing"). The present invention also relates to the use of a laser or LED for the detection or measurement of H2S concentrations in a liquid sample between 0.01 μM and 1000 μM, preferably 2 to 400 μM. The present invention also relates to the use of a porous hybrid solid of the MOF ("Metal Organic Framework") type having -N3 groups on its external surface or in its pores, for the detection or measurement of 20 concentrations of H2S. in a liquid sample between 0.01 μM and 1000 μM, preferably 2 to 400 μM. Advantageously, in the aforementioned uses, the liquid sample may be a biological sample, or may be from a biological sample, and the concentration of H2S is indicative of a disease, which may be cancer, diabetes, Down syndrome (trisomy 21), Alzheimer's disease or cardiovascular diseases such as hypertension. The present invention offers numerous advantages, including: - signal gain / decrease of the detection limit for the detection of pathological / physiological 1-12 S / S 2 - concentrations below 100 pmol / L - performed with a solid porous (MOF-N3), easily isolatable, manipulable, recyclable, and which can potentially be shaped (for example as a thin layer, thus allowing an improvement in the sensitivity of the system) - the solid MOF-N3 does not There is no toxicity problem, and thus allows the practice of the present invention for the diagnosis of human or animal subjects - 1-12S / S2-selective system in the presence of cysteine or phenylthiol. - the response time in the presence of 1-12S / S2- is of the order of one minute - proportionality of the response vs. H2S concentration - reproducibility of the method.
    [0022] Other advantages may still be apparent to those skilled in the art upon reading the examples below, with reference to the appended figures, given for illustrative and non-limiting purposes. BRIEF DESCRIPTION OF THE FIGURES Figure 1: Examples of MOF-N3 that may be used in the process and apparatus of the invention. Figure 2: Integral calibration curve = f ([Na2S]) for the MOF Al-MIL-101-N3, according to the method of the invention. Figure 3: Photoluminescence measurement with a continuous Xe lamp of MOF Al-MIL-101-N3 exposed to high Na2S concentrations (see Comparative Example 3). Figure 4: Photoluminescence measurement with a laser of Al-MIL-101-N3 exposed to low concentrations of Na2S, according to the method of the invention (see Example 4).
    [0023] Figure 5: Example of photoluminescence spectrum harvested for In-MIL-68-N3 MOF according to the method of the invention. FIG. 6: Examples of photoluminescence spectra harvested for the ZrUiO-66-N3 MOF according to the method of the invention.
    [0024] FIG. 7: Diagram of an example of optical assembly that can be used to implement the method according to the invention: 1. source, 2. monochromator, 3. collimator, 4. mirror, 5. sample holder , 6. collector with parabolic mirror, 7. optical fiber, 8. spectrometer / CCD sensor, 9. computer 5 processing of the signal. The monochromator 2 is not necessary when one excites with a laser; this one is used when the excitation is done with a lamp emitting the white light. EXAMPLES Example 1 - General Protocol The protocol below is generalizable to any type of MOF solid having -N3 groups on its outer surface or in its pores. 10 mg of MOF-N3 is suspended in 0.8 ml of a liquid sample to be analyzed. After 2 minutes of reaction, the solid is isolated by centrifugation, washed with the solvent of the analyte and then with chloromethane, and dried under primary vacuum at room temperature. This dry solid is then spread in the form of a thin layer of about 1 cm 2 of thickness between 0.1 and 0.5 mm on a silicon support of 1 × 10 cm (Neyco) and placed in the optical measuring system. The thin film of MOF is irradiated with a laser at an excitation wavelength of 343 nm (in this case the elements 2 and 3 can be omitted in FIG. 7), and the photoluminescence shown in FIG. its photoluminescence spectrum is collected by a detector (emission wavelengths from 530 to 580 nm). Photoluminescence measurements are carried out at room temperature under laser irradiation. The laser used is a femto-second pulsed laser with ytterbium (Mikan model, Amplitude Systems). Its average power is 3 mW, at the excitation wavelength of 343 nm, the irradiation time is <250 fs with a repetition frequency of 54 MHz. The spectral decomposition of the photoluminescence signal was performed with a spectrometer (Horiba JobinYvon iHR-320) and was detected by a nitrogen cooled CCD camera (Horiba Symphony 1024x256). As a standard, the collected raw photoluminescence spectrum is corrected by an optical transfer function characteristic of the installation. The transfer function is obtained by dividing the signal measured by the detector from a source of white light by the theoretical spectrum of this source. Example 2 - Establishment of a calibration curve The protocol of Example 1 is used. Briefly, 10 mg of Al-MIL-101-N3 MOF is suspended in 0.8 mL of a dimethylsulfoxide solution containing a known concentration of Na2S of 2 nM and 100 μM (four calibration points at the following concentrations: 2 μM, 26 μM, 100 μM and 420 μM). This dry solid is then spread in the form of a thin layer on a silicon support and placed in the optical photoluminescence measuring system illustrated in FIG. 7 according to the protocol described in Example 1. The calibration curve is drawn from the integral intensity of the harvested photoluminescence spectrum (value of the area under the spectrum between 500 and 600 nm, calculated using the standard option proposed by the Origin software, for example.
    [0025] See Figure 2. We observe the calibration curve illustrating the function that links the integral intensity of the photoluminescence of MOF and the concentration of [Na2S]. Example 3 - Comparative Example: Photoluminescence measurement with a UV exciting lamp of Al-MIL-101-N3 MOF exposed to high Na2S concentrations 10 mg of MOF Al-MIL-101-N3 is suspended in 0, 8 mL of a dimethylsulfoxide solution containing a known concentration of Na2S of 120 mM and 4 mM (following concentrations: 169 μM, 6.47 mM, 37.69 mM, 47.81 25 mM, 56.25 mM). This solid, isolated by filtration and dried, is then spread as a thin layer on a silicon support and placed in an optical photoluminescence measuring system with a continuous Xe lamp, with an electric power of 450W and offering a range of wave ranging from 200 to 1000 nm. The thin layer of MOF was irradiated, and the photoluminescence measurements were performed at room temperature using UV lamp excitation at 334 nm and emission measurement at 436 nm (Figure 3). Irradiation of the sample of MOF Al-MIL-101-N3, reacted with a solution containing Na2S / H2S, with a UV lamp allows the reproduction of a signal 3034200 27 with a maximum intensity of photoluminescence at 400. -500 nm. However, the peak at 400-500 nm does not allow a calibration of the amount of Na2S / H2S in solution for low concentrations, less than 100 micromolar. For concentrations above 100 μM and UV irradiation, the response Integrale = f ([Na 2 S]) is linear. Example 4 - Photoluminescence measurement with an Al-MIL101-N3 MOF laser exposed to low Na2S concentrations The protocol of Example 1 is used, with the following concentrations of [Na2S]: 2 pM, 26 pM, 100 pM and 420 μM. Under irradiation with a laser, the maximum photoluminescence at 400500 nm disappears and a new maximum at 500-600 nm becomes dominant. The 500-600 nm peak is characteristic of another type of electronic transition within the Al-MIL-101-N3 MOF ligand and allows calibration for concentrations of 2-400 micromolar (Figure 4). The electron transition observed with the peak at 500-600 nm is visible with laser irradiation, but not with a UV lamp (see Comparative Example 3). Example 5 Photoluminescence Measurement with a MOF Laser In-MIL-6820 N3 The protocol of Example 1 is used, with 10 mg of In-MIL-68-N3 MOF and a [Na2S] concentration of 100 μM ( Figure 5). Example 6 Photoluminescence Measurement with a MOF Zr-UiO-66-N3 Laser The protocol of Example 1 is used, with 10 mg of Zr-UiO-66-N3 MOF and a concentration of [Na2S] of pM and 100 μM (Figure 6).
    [0026] 3034200 28 LIST OF REFERENCES 1. Coordination Chemistry reviews 257 (2013) 2335-2347. 2. Scientific Reports 4: 5870, 2014, pp. 1-9 5 3. Scientific Reports 4: 7053, 2014, pp. 1-6 4. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295: R1479-1485, 2008 5. FR2958945 6. WO 2011/48283 & FR2951723 7. WO 2011/48280 & FR2951725 10 8. WO 2011/33185 & FR2950347 9. WO 2011/48282 & FR2951724 10. Goto et al. in Journal of the American Chemical Society 2008, 130, 14354 11. WO 2009/77670 12. WO 2009/77671 13. Inorganic Chemistry 2008, 47, 7568 14. Chemical Communications 2011, 47, 2838 15. Microporous and Mesoporous Materials 2012 , 164, 38 16. WO 2011/048284 17. Journal of Material Chemistry 2012, 22, 10210 18. Inorganic Chemistry 2009, 48, 296-306 19. Angewandte Chemie - International Edition 2009, 48, 5163 20. Chemistry of Materials 2010, 22, 6632-6640 21. Kim et al., Chemical Science 2012, 3, 126 22. WO 2010/43832 23. CAU-10-NH 2: Chem. Mater., 2012, 25, 17-26
    权利要求:
    Claims (16)
    [0001]
    REVENDICATIONS1. A method for detecting and measuring traces of H2S in a liquid sample, said method comprising the following steps: a) contacting for 1 to 10 minutes, preferably 2 minutes, a liquid sample to be analyzed with a porous hybrid solid of MOF ("Metal Organic Framework") type having -N3 groups on its outer surface or in its pores; b) subjecting the hybrid porous solid of the MOF type to laser irradiation or LED of wavelength 300-400 nm, preferably 343 nm; the hybrid porous solid of the MOF type being previously isolated from the liquid sample and disposed on a two-dimensional support, or being suspended in the liquid sample inside a transparent-ultraviolet-walled container adapted to contain liquids; c) measuring the intensity of the photoluminescence signal emitted by the solid disposed on the support or in the container in the spectral zone 500-600 nm; and d) determining the concentration of H2S present in the sample from the photoluminescence signal thus measured using a previously established calibration curve.
    [0002]
    2. Method according to claim 1, wherein the calibration curve used in step d) is established according to a process comprising the following steps: al) putting in contact for 1 to 10 minutes, preferably 2 minutes, a liquid sample containing a given concentration of S2-, with an M amount of porous hybrid MOF ("Metal Organic Framework") solid having -N3 groups at its outer surface or in its pores; 131) subjecting the hybrid porous solid of the MOF type to a laser irradiation of wavelength of 300-400 nm, preferably 343 nm; the hybrid porous solid of the MOF type being previously isolated from the liquid sample and placed on a two-dimensional support, or in suspension 3034200 in the liquid sample inside a transparent-ultraviolet-walled container adapted to contain liquids; c) measuring the intensity of the photoluminescence signal emitted in the 500-600 nm spectral region; Dl) repeat steps a1 to c1) with a series of at least 4 different [SI concentrations between 0.01 μM and 1000 μM, preferably 2 to 400 μM; el) draw the calibration curve from the values of the integral intensity corresponding to the area under the photoluminescence spectrum measured between 500 and 600 nm, showing on the abscissa the concentration of Na2S and on the ordinate the value of the integral intensity of photoluminescence.
    [0003]
    3. The process according to claim 1, wherein the traces of H2S present in the sample analyzed are between 0.01 μM and 1000 μM, preferably 2 to 400 μM.
    [0004]
    4. The method of claim 1 or 2, wherein the two-dimensional support is a silicon support, on which are optionally deposited metal nanoparticles and / or semiconductors.
    [0005]
    5. The method of claim 4, wherein the two-dimensional support is coated with a thin layer of MOF. 25
    [0006]
    6. The method of claim 1 or 2, wherein the transparent-walled container is a parallelepipedic or cylindrical quartz cup. 30
    [0007]
    The method of any one of claims 1 to 6, wherein the laser irradiation is produced by a pulsed or continuous laser, preferably pulsed. 3034200 31
    [0008]
    The method of any one of claims 1 to 7, wherein the photoluminescent signal is detected by means of a CCD camera.
    [0009]
    9. A process according to any one of claims 1 to 8, wherein the sample to be analyzed is a biological sample.
    [0010]
    The process according to any one of claims 1 to 9, wherein at least one of the organic ligands of MOF is selected from the group consisting of: ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR1 ## C0 2 CO 2 (RL 3) t 02c (RI-3) -O C CO2-3034200 32 CO2-CO2-CO2-> /> (RI-3) t (RI-3) t CO2-CO2-CO2- (RI-3) t (RL3) t 02C / / C02- -02C CO2_ (RI-3) t / / (R1-3) t 02C CO2 (RL3) t 1 (RL3) t -1 CO2 02C / NK / -02C CO2- (RI-3) t5 NN -0C ---- (RI-3) t 2 CO2-A2 A1 independently 1 ÷ (R1-3) t A, .D where At, A2 and A3 are (R1-3) tL3 (R) t / / CO2-3034200 33 in which: each occurrence of t is independently an integer of 1 to 4 depending on the valency of the aromatic radical, and each occurrence of RL3 independently represents H, halogen (preferably F, Cl or Br), OH, N3, NH2, NO2 or C1-C6 alkyl (preferably methyl or ethyl); provided that at least one occurrence of RL3 is N3.
    [0011]
    The process according to claim 10, wherein said at least one of the organic ligands of MOF is selected from an azide terephthalate ligand of the following formula: ## STR2 ## wherein t represents an integer of from 1 to 4, preferably 1 ; and an azide-biphenyl-dicarboxylate ligand of the following formula: wherein t1 and t2 independently represent an integer of 0 to 4 with the proviso that t1 and t2 are not both 0, preferably t1 and or t2 is (nt) 1, more preferably t1 or t2 is 1. 20
    [0012]
    The process according to any one of claims 1 to 9, wherein the MOF is selected from Al / Cr / Fe-MIL-101-N3, In / Al-MIL-68-N3, Al / Fe-MIL53-N3. , DMOF-1-N3, CAU-1-N3, CAU-10-N3, Zr-U10-66-N3, or UMCM-1-N3; preferably In-MIL-68-N3, Zr-U10-66-N3 or Al-MIL-101-N3; preferably Al-MIL101-N3. 25 3034200 34
    [0013]
    13. A device for detecting and measuring traces of H2S in a liquid sample, comprising: i) a receptacle adapted to receive a two-dimensional support coated with a thin layer of a porous hybrid solid of the MOF type ("Metal Organic" Framework ") having -N3 groups on its outer surface or in its pores; or a clear-walled vessel containing a liquid medium in which a porous hybrid MOF-type ("Metal Organic Framework") solid having -N3 groups on its outer surface or in its pores is suspended; Ii) a light source selected from a laser or LED, preferably a pulsed laser, for irradiating at 300-400 nm, preferably 343 nm; and iii) a detector adapted for detecting a photoluminescence signal at 500-600 nm. 15
    [0014]
    14. Use of a porous MOF ("Metal Organic Framework") hybrid solid having -N3 groups on its outer surface or in its pores for the detection or measurement of H2S concentrations in a liquid sample between 0.01 pM and 1000 μM, preferably 2 to 400 μM. 20
    [0015]
    The use of claim 14, wherein the liquid sample is a biological sample, and the concentration of H2S is indicative of a disease.
    [0016]
    16. Use according to claim 15, wherein the disease is cancer, diabetes, Down syndrome (trisomy 21), Alzheimer's disease, or cardiovascular diseases such as hypertension.
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    FR1552431A|FR3034199A1|2015-03-24|2015-03-24|METHOD FOR IN VITRO DETECTION OF H2S FROM LUMINESCENT MOF|PCT/FR2016/050640| WO2016151245A1|2015-03-24|2016-03-23|Method for in-vitro detection of h2s from luminescent mofs|
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