FLUORIMETRIC ANION SENSORS (Machine-translation by Google Translate, not legally binding)

专利摘要:
Fluorimetric anion sensors. The present document describes copolymers, as well as methods of obtaining them, wherein said copolymers comprise a salt of a moiety of formula (I): {IMAGE-01} where one of the groups R3 , R4 , R5 , R6 , R7 , R8or R9is a group OR10 , and the rest of the groups are each independently selected from H , OH, halogen, sulfonyl, NR11R12 , COOR10 , CONR11R12 , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; where R10is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R11and R12are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl. Said copolymers are applicable in the detection of anions, and in particular of chlorides in industrial waters and waters for human consumption, or in sweat. These copolymers can therefore be used as continuous chloride detectors (in the case of industrial or human consumption waters), as well as in dressings (in the case of sweat) for the diagnosis of diseases. (Machine-translation by Google Translate, not legally binding)
公开号:ES2695246A1
申请号:ES201730844
申请日:2017-06-27
公开日:2019-01-02
发明作者:Calzada Saúl Vallejos；Pérez José Miguel García；García Félix García；Arenas Felipe Serna；Mata Ernesto José Rodriguez；Pato Roberto Quesada；Santa Cruz Elsa Hernando；Valverde María García
申请人:Universidad de Burgos；
IPC主号:

专利说明:

[0001]
[0002]
[0003] OBJECT OF THE INVENTION:
[0004]
[0005] The present invention is related to the preparation of new polymeric materials that behave as fluorimetric sensors for anions and, in particular, for chlorides, in aqueous media, such as, for example, industrial waters, waters for human consumption and / or sweat.
[0006]
[0007] BACKGROUND OF THE INVENTION:
[0008]
[0009] Nowadays there are numerous norms and / or directives that are applied in the field of the control of chemical species in industrial waters and waters for human consumption (Royal Decree 140/2003, of February 7). Among these chemical species, various anions, among which chloride anions are found, are measured weekly, since they can vary a lot and very quickly. Chlorine salts are usually used to prevent the growth of microorganisms in waters for human consumption. A defect in the levels of these chlorine salts can favor the growth of microorganisms, however, an excess can also cause the concentrations of chloride anions to grow exponentially, with all the health risks that this entails.
[0010]
[0011] Among the most commonly used methods for the detection of chlorides in waters, the selective chloride ion electrode stands out. It is basically a device that translates the concentration of chlorides into an electrical signal that is subsequently analyzed and interpreted. Obviously, the equipment requires an electrical outlet for its operation, in addition to a calibration prior to the measurement.
[0012]
[0013] There are also methods based on the precipitation of insoluble chloride salts, such as silver chloride. In this case, the technique requires manipulating various chemical reagents, some of which reach quite high prices, which also supposes a limitation when carrying out routine tests.
[0014]
[0015] Regarding the methods used for the detection of chlorides in sweat, the so-called "sweat test" or "Method of Gibson and Cooke" (G. Mastella, G. Di Cesare, A. Borruso, L. Menin, L. stands out). Zanolla, Acta Pediatr., 2000, 89, 933-937), which is applied especially in young patients as a simple method for the pre-diagnosis of cystic fibrosis and whose procedure is widely detailed in the bibliography (VA LeGrys , JR
[0016] Yankaskas, L. M. Quittell, B. C. Marshall, P. J. Mogayze, J. Pediatr., 2007, 151, 1.85-89). A high concentration (above 60 millimoles per liter) of chlorides in the sweat, is one of the most representative symptoms of the fibrosis qdstica. Currently there are several examples of kits marketed for the realization of this test. All of them are based on three steps: (1) the stimulation of sweat glands by iontophoresis (J. Guodemar, P. Garda, EM Rodriguez, Journal of the Faculty of Health Sciences, 2004, 2, "Iontophoresis, dose and treatments ") and with the help of pilocarpine (I. Largo-Garda, Rev. Ped. Elec., 2009, 6, 1-18), (2) sample collection, and (3) analysis.
[0017]
[0018] In addition to chemical fibrosis, there are other diseases related to a high concentration of chlorides in sweat, such as: untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis syndrome, hypothyroidism, malnutrition, mauric syndrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency.
[0019]
[0020] In this framework, the development of polymers and copolymers based on monomers with different functionalizations and in the form of hydrolytic membranes that have gel behavior, and that detect different chemical species, both in solution and gas phase, is a subject of great interest Scientists (S. Vallejos, A. Munoz, S. Ibeas, F. Serna, F. Garda, JM Garda, J. Mater, Chem. A. 2013, 1, 15435-15441, S. Vallejos, A. Munoz, S. Ibeas, F. Serna, F. Garda, JM Garda, J. Hazard, Mater 2014, 276, 52-57, S. Vallejos, A. Munoz, S. Ibeas, F. Serna, F. Garda, JM Garda , ACS Appl. Mater. Interfaces, 2015, 7, 921-928, JL Pablos, S. Vallejos, A. Munoz, MJ Rojo, F. Serna, FC Garda, JM Garda, Chem. Eur. J. 2015, 21, 8733-8736, S. Vallejos, A. Munoz, F. Garda, R. Colleoni, R. Biesuz, G. Alberti, JM Garda, Sens. Actuators B. 2016, 233, 120-126). The aforementioned materials can be in the form of a membrane (for use in the detection of chlorides in aqueous media) or, even, in the form of a dressing (for use as an alternative to the sweat test).
[0021]
[0022] BRIEF DESCRIPTION OF THE INVENTION
[0023]
[0024] The present invention relates to a copolymer comprising a salt of a radical of formula (I):
[0025]
[0026]
[0027] where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is an OR ¹⁰ group, and the rest of the groups are each independently selected from H, OH, halogen, sulfonyl , NR ¹¹ R ¹² , COOR ¹⁰ , CONR ¹¹ R ¹² , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; wherein R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R ¹¹ and R ¹² are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl.
[0028]
[0029] Another aspect of the present invention relates to a method of obtaining a copolymer comprising a salt of a residue of formula (I):
[0030]
[0031]
[0032]
[0033]
[0034] wherein said method comprises the steps of:
[0035]
[0036] (a) obtaining a copolymer by polymerizing at least two monomers, where at least one of said two monomers, is a monomer Z comprising a group R ² , where:
[0037] - said group R ² comprises an aromatic ring or a non-aromatic ring and / or an aliphatic chain, and
[0038] - R ² is, in addition, replaced with at least one halogen,
[0039] and wherein said polymerization is carried out by direct reaction of polymerizable groups present in each of the monomers;
[0040] (b) reaction of the copolymer obtained in step (a) with a compound of formula (la):
[0041]
[0042]
[0043]
[0044]
[0045] where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is an OR ¹⁰ group, and the rest of the groups are each independently selected from H, OH, halogen, sulfonyl , NR ¹¹ R ¹² , COOR ¹⁰ , CONR ¹¹ R ¹² , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; wherein R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R ¹¹ and R ¹² are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl.
[0046]
[0047] The present invention also relates to a copolymer comprising a salt of a residue of formula (I), obtainable by the obtaining method described in the present invention.
[0048]
[0049] Another aspect of the present invention relates to the use of a copolymer comprising a salt of a residue of formula (I), of the present invention, for the detection and / or quantification of anions, and in particular of chlorides.
[0050]
[0051] A further aspect of the present invention relates to the use of a copolymer comprising a salt of a residue of formula (I), of the present invention, for the detection of a disease independently selected from cystic fibrosis, untreated adrenal insufficiency, dysplasia ectodermal, familial cholestasis smdrome, hypothyroidism, malnutrition, mauric smdrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic diabetes insipidus, fucosidosis, nephrosis or glucose 6-phosphate deficiency.
[0052]
[0053] Another aspect of the present invention relates to a dressing comprising a copolymer which in turn comprises a salt of a residue of formula (I), of the present invention, for the detection of a disease independently selected from cystic fibrosis, adrenal insufficiency. untreated, ectodermal dysplasia, familial cholestasis smdrome, hypothyroidism, malnutrition, mauric smdrome, storage disease type 1 glycogen, mucopolysaccharidosis, nephrogenic insidious diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency.
[0054]
[0055] DESCRIPTION
[0056]
[0057] The present invention thus relates to a co-polymer comprising a salt of a residue of formula (I)
[0058]
[0059]
[0060]
[0061]
[0062] where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is an OR ¹⁰ group, and the rest of the groups are each independently selected from H, OH, halogen, sulfonyl , NR ¹¹ R ¹² , COOR ¹⁰ , CONR ¹¹ R ¹² , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; wherein R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R ¹¹ and R ¹² are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl.
[0063]
[0064] For the purposes of the present invention, examples of salts of the rest of formula (I) comprise salts of an organic or inorganic acid. In one embodiment said salt is independently selected from a salt of fluoride, chloride, bromide, iodide, sulfate, sulfite, phosphate, carbonate, bicarbonate, nitrate, nitrite, hydroxide, acetate, lactate, citrate or oxalate. Generally, in one embodiment of the invention, said salt comprises any anion present in industrial waters, waters for human consumption, or in sweat. In one embodiment of the invention, the salt is a fluoride, chloride, bromide or iodide salt, more preferably bromide.
[0065]
[0066] For the purposes of the present invention, the term "alkyl" refers to a straight or branched aliphatic hydrocarbon chain of 1 to 20 carbons which may or may not have different substitutions In a preferred embodiment said alkyl is independently selected from methyl, ethyl or propyl.
[0067] For the purposes of the present invention, the term "cycloalkyl" refers to a hydrocarbon dichloride group which may or may not have different substitutions In a preferred embodiment said cycloalkyl is independently selected from cyclopropyl, cyclopentyl or cyclohexyl.
[0068]
[0069] For the purposes of the present invention the term "alkoxy" refers to a hydrocarbon group attached to an oxygen atom such as OR ^10. In a preferred embodiment said alkoxy group is independently selected from methoxy, ethoxy, butoxy, propoxy, isopropoxy, tert -butoxy, phenoxy In a more preferred embodiment said alkoxy group is methoxy.
[0070]
[0071] For the purposes of the present invention the term "heterocycle" refers to an aliphatic hydrocarbon ring, having at least one heteroatom, and which may or may not have different substitutions In a preferred embodiment said heterocycle is independently selected from piperidyl, pyrrolidine, tetrahydropyran , tetrahydrofuran or tetrahydrothiophene.
[0072]
[0073] For the purposes of the present invention the term "aryl" refers to a group which may comprise one or more hydrocarbon aromatic rings substituted or unsubstituted with other functional groups In a preferred embodiment said aryl group is independently selected from phenyl or naphthyl.
[0074]
[0075] For the purposes of the present invention the term "hetaryl" refers to a group which may comprise one or more aromatic rings comprising one or more heteroatoms In a preferred embodiment said hetaryl group is independently selected from pyridyl, pyrrole, pyran, furan or thiophene.
[0076]
[0077] Said residue of formula (I) interacts with anions, and in particular with chlorides, producing a change in the fluorescence of the copolymer and, therefore, allowing the detection and / or quantification of said anions. In particular, the fluorescence of the material is reduced, that is, a process of switching off (ON-OFF) the fluorescence occurs.
[0078] This process can be observed in a fluorometer (fluorescence spectrophotometer). In the case of the detection of chloride anions, the fluorescence band centered at about 440 nm (observed when the sample is excited at 321 nm), begins to decrease, until practically its disappearance, as the concentration of chlorides increases. the middle. The change in fluorescence is so great that, in addition to a fluorometer, the change can also be appreciated qualitatively at a glance.
[0079] Furthermore, the use of the copolymers of the present invention is completely reversible, so that if said copolymer is washed with water, once used for the detection of an anion, it becomes fully operative again.
[0080]
[0081] The copolymers of the present invention are, therefore, applicable in the detection and / or quantification of anions, and in particular of chlorides. One embodiment refers to the use of copolymers comprising a salt of a residue of formula (I) for the detection and / or quantification of anions and, in particular, of chlorides in industrial waters and in waters for human consumption.
[0082]
[0083] In addition, the copolymers of the present invention are biocompatible for their application in the detection and / or quantification of chlorides in sweat. This property of detection and / or quantification of chlorides by immersion of the copolymer of the invention in an aqueous medium, or simply by contact, in the case of sweat, results in these copolymers being used as continuous chloride detectors (in the case of industrial waters or of human consumption), as well as in a dressing (in the case of sweat) that contains them.
[0084]
[0085] Therefore, another embodiment relates to the use of the copolymers of the invention for the detection and / or quantification of chlorides in sweat.
[0086]
[0087] The detection of the amount of chlorides in sweat, through the use of the copolymers of the present invention, is applicable in the detection and diagnosis of diseases related to a high concentration of chlorides in sweat, such as cystic fibrosis, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis smdrome, hypothyroidism, malnutrition, mauric smdrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency.
[0088]
[0089] Therefore, an embodiment refers to the use of the copolymers of the invention for the detection of a disease related to a high concentration of chlorides in the sweat. Preferably, said disease is independently selected from cystic fibrosis, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis smdrome, hypothyroidism, malnutrition, mauric syndrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or deficiency of glucose 6 phosphate. More preferably, said disease is cystic fibrosis.
[0090] The method of detection and / or quantification of chlorides described in the present invention is based, therefore, on the capacity of said chloride anions to eliminate the florescence of the rest of the formula (I) present in the copolymers of the present invention. Said residue of formula (I), present in the copolymers of the present invention, is a group derived from quinoline linked to the polymer chain by the nitrogen atom of the quinoline, and wherein said nitrogen atom is a positively charged quaternary nitrogen.
[0091]
[0092] The copolymers of the present invention, which comprise at least one salt of a radical of formula (I), can be linear or crosslinked copolymers.
[0093]
[0094] The term "polymer" refers to a molecule comprising one or more structural units that are repeated successively. These units are called monomers. The polymers are obtained by the repetitive union of said monomers by reaction of reactive groups (or polymerizable groups) present in each of the monomers, in a process called polymerization. A copolymer therefore comprises more than one different monomer, and is obtained, therefore, by polymerization of at least two or more different monomers.
[0095]
[0096] It is called a crosslinked copolymer, a copolymer that forms a network formed by the union of different polymer chains. The formation of said network from different polymer chains is called crosslinking.
[0097]
[0098] Copolymers comprising a salt of a residue of formula (I), described in the present invention, are presented in the form of solid films or membranes. Said solid membranes can be dense membranes, or porous membranes. The present invention relates to said dense membranes, but also to the porous membranes obtained by chemical and / or physical foaming processes, carried out from the dense membranes previously described.
[0099]
[0100] Copolymers comprising a salt of a residue of formula (I), described in the present invention, exhibit fluorescence changes in the presence of anions. For the purposes of the present invention are non-limiting examples of anions, the chloride [Cl-], the bromide [Br-], the iodide [I-], or the acetate [CH ³ COO-]. In a preferred embodiment said fluorescence change occurs when there are chloride anions present in the medium.
[0101]
[0102] For the purposes of the present invention, the term copolymer is used in an equivalent manner to the term membrane, due to the membrane structure exhibited by the copolymers described herein. Also, the linear or crosslinked copolymers that they comprise a salt of a residue of formula (I), described in the present invention, are referred to indistinctly sensor membrane, sensor co-polymer, or fluorogenic sensors, due to the properties they present, described in this document.
[0103]
[0104] One embodiment of the present invention relates to a method of obtaining a copolymer comprising a salt of a residue of formula (I):
[0105]
[0106]
[0107]
[0108]
[0109] wherein said method comprises the steps of:
[0110]
[0111] (a) obtaining a copolymer by polymerizing at least two monomers, where at least one of said two monomers is a monomer Z comprising a group R ² where,
[0112] - said group R ² comprises an aromatic ring, a non-aromatic ring and / or an aliphatic chain, and
[0113] - R ² is also substituted with at least one halogen,
[0114]
[0115] and wherein said polymerization is carried out by direct reaction of polymerizable groups present in each of the monomers;
[0116]
[0117] (b) reaction of the copolymer obtained in step (a) with a compound of formula (la): where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is an OR ¹⁰ group, and the rest of the groups are each independently selected from H, OH, halogen, sulfonyl , NR ¹¹ R ¹² , COOR ¹⁰ , CONR ¹¹ R ¹² , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; wherein R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R ¹¹ and R ¹² are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl.
[0118]
[0119] In a preferred embodiment, one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a group OR ¹⁰ , and the rest of the groups is H; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl.
[0120]
[0121] In a preferred embodiment, one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a methoxy group, and the rest of the groups is H.
[0122]
[0123] In an even more preferred embodiment R ⁵ is an OR ¹⁰ group and the rest of the groups is H; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl.
[0124]
[0125] In a still more preferred embodiment R ⁵ is a methoxy group and the rest of the groups is H.
[0126]
[0127] In another preferred embodiment one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a group OR ¹⁰ , and the rest of the groups are each independently selected from H or CH ³ ; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl. More preferably R ¹⁰ is methyl.
[0128]
[0129] In a more preferred embodiment R ⁵ is an OR ¹⁰ group and the rest of the groups are each independently selected from H or CH ³ ; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tertbutyl. More preferably R ¹⁰ is methyl.
[0130]
[0131] In another preferred embodiment one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a group OR ¹⁰ , and the rest of the groups are each independently selected from H or sulfonyl; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl. More preferably R ¹⁰ is methyl.
[0132]
[0133] In a more preferred embodiment R ⁵ is an OR ¹⁰ group and the rest of the groups are each independently selected from H or sulfonyl; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tertbutyl. More preferably R ¹⁰ is methyl.
[0134]
[0135] The monomers used in step (a) described in the present invention can be commercial monomers as well as monomers of synthesis.
[0136]
[0137] In a preferred embodiment of the present invention, the reaction of step (b) between the copolymer obtained in step (a) and a compound of formula (la) comprises:
[0138]
[0139] i. performing a dip of the copolymer obtained in step (a) in said compound of formula (Ia), or in a solution thereof, at a temperature of between 0 ° C and 150 ° C for at least 5 hours,
[0140]
[0141] ii. performing a dip of the copolymer obtained in step (i) in an organic solvent, and repeating this process until the compound of formula (Ia) that has not reacted is eliminated,
[0142]
[0143] iii. performing a dip of the copolymer obtained in step (ii) in distilled water.
[0144] In an embodiment of the invention, step (b) comprises (i) immersing the copolymer obtained in step (a) in a compound of formula (I), or in a solution thereof, at a temperature of between ° C and 100 ° C for at least 5 hours.
[0145]
[0146] In an embodiment of the invention, step (b) comprises (i) immersing the copolymer obtained in step (a) in a compound of formula (I), or in a solution thereof, and heating at a temperature between between 50 ° C and 150 ° C for at least 12 hours.
[0147] In an embodiment of the invention, step (b) comprises (ii) immersing the copolymer obtained in step (i) in an organic solvent, and repeating this process at least 5 times. In a preferred embodiment of step (b) of the present invention comprises (ii) immersing the copolymer obtained in step (i) in an organic solvent, and repeating this process at least 5 times, each of said dives of minutes of duration.
[0148] In a preferred embodiment of the invention, step (b) comprises (ii) carrying out an immersion of the copolymer obtained in step (i) in an organic solvent, and repeating this process until the compound of formula (la) which has not been reacted, wherein said organic solvent is an organic solvent miscible with water.
[0149]
[0150] For the purposes of the present invention the term "organic solvent miscible with water" refers to any organic solvent that can be mixed in any proportion with water, the resulting mixture being a homogeneous mixture or solution.
[0151]
[0152] In a more preferred embodiment said organic solvent is selected from acetone, dimethylformamide, acetonitrile, dimethylacetamide, dimethylsulfoxide, N-methylpyrrolidone, methanol, ethanol, isopropanol or THF. In a still more preferred embodiment said organic solvent is acetone.
[0153]
[0154] For the purposes of the present invention, the copolymers resulting from step (a) are obtained by polymerization, wherein said polymerization is carried out by direct bonding or reaction between monomers, wherein said monomers comprise polymerizable groups responsible for the polymerization reaction that gives rise to the polymer.
[0155]
[0156] For the purposes of the present invention, non-limiting examples of polymerizable groups are the vinyl, methacrylate, acrylate, methacrylamide or acrylamide group:
[0157]
[0158]
[0159] group vinyl group g i r r u ^ po 0R
[0160] acrylate methacrylate
[0161]
[0162]
[0163]
[0164] group group
[0165] methacrylamide acrylamide
[0166]
[0167] where Ra = Rb = R is a group each independently selected from H, alkyl, alkenyl, aryl or an R ² group, wherein said R ² group is a group comprising an aromatic ring, a non-aromatic ring and / or an aliphatic chain, and where said R ² is found further substituted with at least one atom of the halogen group as defined above.
[0168]
[0169] For the purposes of the present invention, the realization of an immersion implies that the copoker is totally submerged in the solution used.
[0170]
[0171] In a preferred embodiment, the copolymer obtained in step (a) is obtained in the presence of a thermal or photochemical initiator.
[0172]
[0173] The group R ² of the monomer Z used in step (a) of the method of the present invention is called, for the purposes of the present description, anchoring group R ² , since said group is responsible for the subsequent union of the remains of formula (I) that act as fluorogenic sensor groups for anions, preferably chlorides.
[0174]
[0175] For the purposes of the present invention, the monomer Z used in step (a) of the method for obtaining the present invention is referred to as an anchor monomer, where said anchor monomer Z comprises an anchor group R ² and a polymerizable group .
[0176]
[0177] The anchor monomer Z comprises an anchor group R ² and a polymerizable group, wherein said polymerizable group is independently selected from vinyl, methacrylate, acrylate, methacrylamide or acrylamide, as described above, and R ² is a group comprising an an aromatic ring, a non-aromatic ring and / or an aliphatic chain, and wherein said R ² is further substituted with at least one atom from the group of halogens as defined above.
[0178]
[0179] In a preferred embodiment, the polymerizable group of the anionic monomer Z is a vinyl group and is called monomer of formula (II):
[0180]
[0181]
[0182]
[0183]
[0184] where R ¹ is independently selected from H or ^{CH 3; R 2} comprises an aromatic ring, a non-aromatic ring and / or an aliphatic chain and wherein R ² is further substituted with at least one halogen.
[0185]
[0186] In a more preferred embodiment the monomer of formula (II) is 5-bromo-1-pentene or 4-bromo-1-butene. In a still more preferred embodiment the monomer of formula (II) is 5-bromo-1-pentene.
[0187] In the same way, the co-polymer obtained in step (a) is called, for the purposes of the present invention, anchor co-polymer, or anchoring membrane, since it comprises anchoring groups R ² which allow according to step (b) ) of the process of the present invention, the subsequent binding of residues of formula (I). Step (b) of the process of the present invention is therefore called, for the purposes of the present invention, the process of anchoring the remains of formula (I).
[0188]
[0189] The process of anchoring and forming remains of formula (I) sensors of step (b) of the process of the present invention, which occurs when a compound of formula (Ia) reacts with the halogen of the anchor group R ^2. , Forming a copolymer comprising a salt of a residue of formula (I), of the present invention, can be represented according to the following Scheme 1:
[0190]
[0191]
[0192]
[0193]
[0194] Scheme1
[0195]
[0196] where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is an OR ¹⁰ group, and the rest of the groups are each independently selected from H, OH, halogen, sulfonyl , NR ¹¹ R ¹² , COOR ¹⁰ , CONR ¹¹ R ¹² , alkyl, cycloalkyl, aryl, heterocycle or hetaryl; wherein R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl; and wherein R ¹¹ and R ¹² are each independently selected from H, alkyl, cycloalkyl, aryl, heterocycle or hetaryl, and where Hal is a halogen that replaces a group R ² , wherein said group R ² forms part of an anchor copolymer obtained according to step (a) described above. Said halogen Hal which replaces the group R ² is independently selected from Fl, Cl, Br or I.
[0197]
[0198] In a preferred embodiment of the invention, the polymerization of at least two monomers of step (a), wherein at least one of said two monomers is a monomer Z, further comprises monomers X and Y, where the proportion of Z represents between 0, 1% to 10% of the total number of monomers, and where the ratio of X to Y is from 1: 9 to 9: 1.
[0199] In a preferred embodiment the ratio of X to Y is 3: 1. In a preferred embodiment Z represents 1% of the total number of monomers.
[0200]
[0201] In another preferred embodiment X represents between 70% to 80%, Y represents between 19% to 29% and Z represents 1%, of the total number of monomers. In another preferred embodiment of invention X represents 74.25%, Y represents 24.75% and Z represents 1%, of the total number of monomers.
[0202]
[0203] In a preferred embodiment of the invention, the X and Y monomers used in step (a) are each independently selected from N-vinyl pyrrolidone, methyl methacrylate, butyl acrylate, butyl methacrylate, methyl acrylate, styrene, acrylate. of 2-hydroxyethyl, 2-hydroxyethyl methacrylate, 2-ethoxyethyl methacrylate, lauryl acrylate, lauryl methacrylate, vinyl acetate, methacrylic acid, methacrylic anhydride, acrylic acid, methacrylamide or 2-N, N-dimethylaminoethyl methacrylate.
[0204]
[0205] In a preferred embodiment the monomers X and Y used in step (a) are each independently selected from N-vinyl pyrrolidone, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, or methyl methacrylate.
[0206]
[0207] In a preferred embodiment of the invention, one of the monomers used in step (a) is N-vinyl pyrrolidone.
[0208]
[0209] In a preferred embodiment of the present invention, one of the monomers used in step (a) is 2-hydroxyethyl acrylate.
[0210]
[0211] In a preferred embodiment of the present invention, the polymerization of at least two monomers of step (a), wherein at least one of said two monomers is a monomer Z, further comprises monomers X and Y, where monomers X and Y are respectively N-vinyl pyrrolidone and 2-hydroxyethyl acrylate. In a more preferred embodiment the monomer Z is 5-bromo-1-pentene or 4-bromobutene. In a still more preferred embodiment the monomer Z is 5-bromo-1-pentene.
[0212]
[0213] In a preferred embodiment of the invention, the polymerization described in step (a) is carried out in solution or in block.
[0214]
[0215] For the purposes of the present invention, it is called block polymerization, or bulk polymerization, to the polymerization technique in which only the monomers and the initiator are present in the reaction medium. In the case that the polymerization is carried out by thermal initiation without the need for an initiator, only monomers are present in the reaction medium.
[0216]
[0217] For the purposes of the present invention, it is called polymerization in solution to the polymerization technique in which in addition to the monomers and initiator, a solvent is used.
[0218] In a preferred embodiment of step (b) of the present invention, the compound of formula (Ia),
[0219]
[0220]
[0221]
[0222]
[0223] where one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a methoxy group, and the rest of the groups is H. In another preferred embodiment one of the R ³ groups, R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a methoxy group, and the rest of the groups is independently selected from H or CH ³ . In another preferred embodiment one of the groups R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ is a methoxy group, and the rest of the groups are each independently selected from H or sulfonyl.
[0224]
[0225] In another preferred embodiment R ⁵ is a group OR ¹⁰ and the rest of the groups is H; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl. More preferably R ¹⁰ is methyl.
[0226]
[0227] In another preferred embodiment R ⁵ is an OR ¹⁰ group and the rest of the groups are each independently selected from H or CH ³ ; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tert-butyl. More preferably R ¹⁰ is methyl.
[0228]
[0229] In a preferred embodiment R ⁵ is an OR ¹⁰ group and the rest of the groups are each independently selected from H or sulfonyl; where R ¹⁰ is selected from alkyl, cycloalkyl, aryl, heterocycle or hetaryl. More preferably R ¹⁰ is an alkyl group, even more preferably R ¹⁰ is selected from methyl, ethyl, propyl, isopropyl, butyl or tertbutyl. More preferably R ¹⁰ is methyl.
[0230]
[0231] In a preferred embodiment of step (b) of the present invention, the compound of formula (la) is 6-methoxyquinoline.
[0232]
[0233] The synthesis of copolymers comprising a salt of a residue of formula (I), described in the present invention, can not be carried out by conventional routes in organic chemicals, ie, (i) by synthesizing a monomer derived from quinoline which has a remainder of formula (I) and, (ii) carrying out a subsequent copolymerization with other commercial monomers, as described in the literature (S. Vallejos, P. Estevez, A. Munoz, S. Ibeas, F. Serna, F. Garda, JM Garda, Sens. Actuators, B, 2011, 157, 686-690). Said conventional process is not possible because the species with formal charges, such as the structure of formula (I), ionic, inhibit the processes of radical polymerization (AA Yassin, J. Polym, Sci., Part A: Polym. ., 1978, 16, 1475-1485, AA Yassin, NA Rizk, POLYMER, 1978, 19, 57-62), and it would therefore be impossible to obtain copolymers comprising a salt of a residue of formula (I) of the invention. by these conventional routes.
[0234]
[0235] However, when performing the synthesis first of an anchor copolymer in step (a) of the obtaining method of the present invention, the species with formal charges of formula (I) is formed once the polymerization is done and the sensor copolymer without problem according to step (b) of the method of the present invention. For this, it is necessary to use an anchor monomer Z comprising a group R ² , responsible for the reaction described in step (b) of the method of the present invention.
[0236]
[0237] In an embodiment of the invention, the polymerization of step (a) of the method of obtaining the invention comprises a monomer Z which is a monomer of formula (II), a monomer X which is a monomer of formula (III), and a monomer And that is a monomer of formula (IV):
[0238] wherein each Ri is independently selected from H or CH ³ , wherein R ² comprises an aromatic ring, a non-aromatic ring and / or an aliphatic chain and wherein, R ² is further substituted with at least one halogen. In a preferred embodiment, the monomer (II) represents between 0.1% to 10% of the total number of monomers and the ratio of the monomer (III) to the monomer (IV) is from 1: 9 to 9: 1 in one embodiment more preferably, the ratio of the monomer (III) to the monomer (IV) is 3: 1. In a more preferred embodiment the monomer (II) represents 1% of the total number of monomers.
[0239] An embodiment of the method for obtaining a copolymer comprising a salt of the rest of formula (I), of the present invention, comprises:
[0240]
[0241] (a) obtaining a copolymer by polymerizing at least two monomers, wherein at least one of said two monomers is a monomer of formula (II), and comprises, in addition, monomers of formula (III) and monomers of formula (IV) ), described above, and wherein said polymerization is carried out by direct reaction of polymerizable groups present in each of the monomers;
[0242] (b) reaction of the copolymer obtained in step (a) with a compound of formula (Ia) described above.
[0243]
[0244] In a preferred embodiment, the compound of formula (Ia) is ^6- methoxyquinoline.
[0245]
[0246] In a preferred embodiment, the monomer (II) represents between 0.1% to 10% of the total number of monomers and the ratio of the monomer (III) to the monomer (IV) is from 1: 9 to 9: 1 in one embodiment more preferably, the ratio of the monomer (III) to the monomer (IV) is 3: 1. In a still more preferred embodiment, the monomer (II) represents 1% of the total number of monomers.
[0247]
[0248] In a preferred embodiment, the polymerization of step (a) of the method of obtaining the invention comprises a monomer Z which is 5-bromo-1-pentene, a monomer X which is N-vinyl pyrrolidone, and a monomer Y which is 2-hydroxyethyl acrylate:
[0249] In a preferred embodiment, 5-bromo-1-pentene represents between 0.1% to 10% of the total number of monomers, and the ratio of N-vinyl pyrrolidone to that of 2-hydroxyethyl acrylate is 1: 9 to 9: 1
[0250]
[0251] An embodiment of the method for obtaining a copolymer comprising a salt of the rest of formula (I), of the present invention, comprises:
[0252]
[0253] (a) obtaining a copolymer by polymerizing at least two monomers, wherein at least one of said two monomers is 5-bromo-1-pentene, and further comprising N-vinyl pyrrolidone and 2-hydroxyethyl acrylate, and wherein said Polymerization is carried out by direct reaction of polymerizable groups present in each of the monomers;
[0254] (b) reaction of the copolymer obtained in step (a) with a compound of formula (la) described above.
[0255]
[0256] In a preferred embodiment, the compound of formula (la) is 6-methoxyquinoline.
[0257]
[0258] In a preferred embodiment, 5-bromo-1-pentene represents between 0.1% to 10% of the total number of monomers and the ratio of N-vinyl pyrrolidone to 2-hydroxyethyl acrylate is from 1: 9 to 9: 1. In a more preferred embodiment, the ratio of N-vinyl pyrrolidone to that of 2-hydroxyethyl acrylate is 3: 1. In a still more preferred embodiment, 5-bromo-1-pentene represents 1% of the total number of monomers.
[0259]
[0260] In general, the polymerization of the monomers in step (a) described in the present invention, whether it comprises commercial or non-commercial vinyl monomers, can be carried out by any of the methods described in the literature for the polymerization of multiple bonds.
[0261]
[0262] The anchor monomers Z, according to what is described in the present invention, can be obtained commercially.
[0263]
[0264] In a preferred embodiment of the present invention, the anchor monomer used in step (a) is 5-bromo-1-pentene, which can be obtained commercially.
[0265]
[0266] The copolymers of the invention possess a three-dimensional structure that permits permeation when placed in contact or immersed in water or other solvents. This fact is the basis for the detection and / or quantification of dissolved anions, such as chlorides. Said permeability can be controlled by varying the proportion between the different monomers used for the preparation of the copolymers.
[0267] Likewise, the copo-komers of the present invention, membranes, films, coatings and materials in solid state that are obtained from these, are characterized by an ideal combination of mechanical properties both in dry, as in swelling, is dedr, with water inside of the polymer network. This converts the copolymers of the present invention into materials suitable for the manufacture of dense membranes that can be used, among other areas, in the detection and / or quantification of anions, such as chloride, in water and / or in aqueous media such as sweat.
[0268]
[0269] That is, the copolymers of the invention are fluorimetric sensors of anions in water and / or in aqueous media such as sweat.
[0270]
[0271] The change of fluorescence by the presence of anions, and in particular of chlorides, is observed by the immersion of the membranes or copolymers comprising residues of formula (I), of the present invention, in the different media without any type of pretreatment of the sample. Therefore, the copolymers of the present invention can be used as sensors for the qualitative or quantitative detection of the anions in question.
[0272]
[0273] Therefore, one embodiment of the present invention relates to the use of a copolymer obtained in the method described in the present invention, or of a copolymer comprising a salt of a residue of formula (I), for the detection and / or quantification of anions, preferably for the detection and / or quantification of chlorides.
[0274]
[0275] An embodiment of the present invention relates to the use of a copolymer obtainable by the method described in the present invention, or of a copolymer comprising a salt of a residue of formula (I), in the detection and / or quantification of anions by at least one method independently selected from:
[0276]
[0277] - detection at a glance; or
[0278]
[0279] - the use of spectroscopic techniques based on fluorescence.
[0280]
[0281] A more preferred embodiment refers to the detection and / or quantification of chlorides in industrial waters or for human consumption. More preferably, the detection and / or quantification of chlorides is carried out in sweat.
[0282]
[0283] Another embodiment relates to the use of a copolymer obtained in the method described in the present invention, or of a copolymer comprising a salt of a residue of formula (I), for the detection of a disease related to a high concentration of chlorides in the sweat; preferably a disease independently selected from fibrosis qwstica, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis smdrome, hypothyroidism, malnutrition, mauric smdrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic insidious diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency. More preferably the disease is qwstica fibrosis.
[0284] One embodiment of the present invention relates to a dressing comprising a copolymer obtained in the method described in the present invention, or a copolymer comprising a salt of a residue of formula (I), for the detection of a disease related to a high concentration of chlorides in the sweat; preferably a disease independently selected from cystic fibrosis, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis syndrome, hypothyroidism, malnutrition, mauric syndrome, glycogen storage disease type 1, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or glucose deficiency 6 phosphate; more preferably for the detection of cystic fibrosis.
[0285]
[0286] An embodiment of the invention also relates to the porous membranes obtained by chemical and / or physical foaming processes from the solid membranes previously described. Examples of the physical foaming process are high-pressure gas dissolution (CO ² and / or N ² ), and some non-limiting examples are included as chemical foaming processes, such as leaching from salts or mixtures of polymers or use of endo or exothermic chemical foaming agents that produce the cellular structure by heating and releasing the gas, and in general any foaming process that originates a porous structure within the solid membrane.
[0287]
[0288] DESCRIPTION OF THE FIGURES
[0289]
[0290] Figure 1. Disappearance of the fluorescence band of a copolymer of the invention prepared according to Example 2 and immersed in MiliQ water. Different amounts of NaCl were added, and the effect on the disappearance of a band in the fluorescence spectrum was analyzed. Figure 1A shows the decrease of the fluorescence band centered at 440 nm as the concentration of chlorides increases in the medium, and which is obtained by exciting the sample at 321 nm; Figure 1B shows the relationship between the added mM chloride concentration and the normalized fluorescence intensity as [1- (Intensity / Initial Intensity)] of said band at 440 nm, and Figure 1C shows the relationship between the logarithm of the added chloride concentration and the normalized fluorescence intensity as [1- (Intensity / Initial Intensity)] of the said band at 440 nm, since in this way they can more easily appreciate the fluorescence intensity values for each of the chloride concentrations tested.
[0291]
[0292] Figure 2. Disappearance of the fluorescence band of a co-polymer of the invention prepared according to Example 2, and immersed in an SS solution simulating the human sweat. Increasing amounts of NaCl / KCl (in a molar range 8.5 / 1.5) were added, from the minimum concentration to the maximum possible present in human sweat (between 6.17 mM and 100.16 mM). The graph shows the relationship between the added chloride concentration and the normalized fluorescence intensity as [1- (Intensity / Initial Intensity)] at 440 nm, which is obtained by exciting the sample at 321 nm.
[0293]
[0294] Figure 3. Reversibility of the use of the copolymers of the invention. The graph shows the cycles of use-washing, which are translated into decrease and growth respectively of the fluorescence band centered at 440 nm, which is obtained by exciting the sample at 321 nm.
[0295]
[0296] EXAMPLES
[0297]
[0298] The following illustrative examples are not intended to be limiting and describe:
[0299]
[0300] (1) Example 1: Preparation of an anchor copolymer according to step (a) of the obtaining method of the present invention comprising a Z-anchor monomer of the vinyl type;
[0301] (2) Example 2: Preparation of a sensor copolymer of the present invention from anchor copolymer obtained in Example 1;
[0302]
[0303] (3) Example 4: Behavior as a fluorimetric sensor of the sensor copolymer obtained in Example 2 against the presence of chloride in water;
[0304]
[0305] (4) Example 5: Behavior as a fluorimetric sensor of the sensor copolymer obtained in Example 2 against the presence of chloride in a simulation of human sweat (SS) prepared in Example 3;
[0306]
[0307] (5) Example 6: Reversibility in the use of the sensor copolymer obtained in Example 2.
[0308] Example 1. Preparation of an anchor copolymer according to step (a) of the obtaining method of the present invention.
[0309] By block copolymerization a membrane with the composition indicated below was prepared. Monomers: N-vinyl pyrrolidone, 2-hydroxyethyl methacrylate and 5-bromo-1-pentene, with a molar ratio of 74.25: 24.75: 1, respectively. Photochemical initiator 2,2-dimethoxy-2-phenylacetophenone, with a weight percentage of 1%. The resulting copolymer solution was injected into a silanized crystal mold, 100 | jm thick, in the absence of oxygen, and placed under a UV lamp overnight to obtain said copolymer in the form of a membrane.
[0310]
[0311] Example 2. Preparation of a sensor copolymer comprising a salt of a residue of formula (I) according to the invention.
[0312]
[0313] For the sensor copolymer preparation, a piece of the membrane prepared in Example 1 was immersed in a test tube with the necessary amount of 6-methoxyquinoline so that the piece of membrane was completely covered by the liquid reagent. The test tube was capped with a piece of parafilm, and kept thermostated at 70 ° C for 12 hours. After that time, the liquid reagent was removed to a vial to be reused, and the piece of membrane was washed several times with acetone. Finally, the membrane was immersed in distilled water, ready for use.
[0314]
[0315] Example 3. Preparation of a simulation of human sweat.
[0316]
[0317] For the preparation of a human sweat simulator solution, the corresponding amounts of the substances specified in Table 1 were weighed.
[0318]
[0319] Table 1 of composition of an aqueous solution that simulates human sweat, which we refer to with the abbreviation "SS." Concentration data of the 12 water-soluble species most abundant in sweat are shown, as well as the amounts of the corresponding salts necessary to prepare the solution, and the resulting concentration of each of them in the mixture.
[0320]
[0321]
[0322]
[0323]
[0324] Table 1
[0325]
[0326] Once weighed, they were dissolved in distilled water, and the solution was placed in a final volume of 1L.
[0327]
[0328] Example 4. Behavior as a fluorimetric sensor of the sensor copolymer of the invention obtained in Example 2 against the presence of chlorides in distilled water.
[0329]
[0330] This example illustrates the behavior as a fluorimetric sensor of a copolymer comprising a salt of a residue of formula (I), whose synthesis is illustrated in Example 2, towards the presence of chlorides in aqueous medium. The introduction of the membrane prepared in Example 2 in distilled water gave rise to a fluorescence spectrum that presented a band from 350 to 600 nm, centered at 440 nm, by exciting the sample at 321 nm. The addition of increasing amounts of sodium chloride between 1,25E-15 and 0.117 M / L produced the disappearance of that fluorescence band as seen in Figure 1A. On the other hand, Figure 1B graphically shows the normalized values of fluorescence intensity versus chloride concentration, which appear in Table 2. The normalized values of fluorescence intensity are shown as 1- (Intensity measured / Initial intensity) indicated as 1- (I / Io) in Table 2 and in Figure 1B:
[0331]
[0332]
[0333]
[0334] Table 2
[0335] The detection Kmite obtained was of 8, 4310-16 moles per liter, and the Kmite of quantification of 2, 5510-15 moles per liter. The limits of detection (LDD) and quantification (LDC) were estimated with the following equations: LDD = 3.3xDE / p and LDC = 10xDE / p where DE is the standard deviation, and p is the slope of the calibration curve in a zone of low chloride content.
[0336]
[0337] Example 5. Behavior as a fluorimetric sensor of the sensor copolymer obtained in Example 2 against the presence of chlorides in a human sweat simulation (SS) prepared according to Example 3
[0338]
[0339] This example illustrates the behavior as a fluorimetric sensor of a copolymer comprising a salt of a residue of formula (I), whose synthesis is illustrated in Example 2, against the presence of chlorides in a medium that simulates human sweat (SS) , whose preparation is illustrated in Example 3. The introduction of the membrane prepared in Example 2, in the solution prepared in Example 3, gave rise to a fluorescence spectrum having a band from 350 to 600 nm, centered at 440 nm, by exciting the sample at 321 nm. The addition of increasing amounts of between 6.17 mM and 100 mM of sodium chloride and potassium chloride, in a molar range of 8.5 / 1.5 respectively, produced the disappearance of that fluorescence band as observed in Figure 2, which reproduces the normalized fluorescence intensity values against the chloride concentration, which appear in Table 3. The normalized values of fluorescence intensity are shown as 1- (Measured intensity / Initial intensity) indicated as 1 - (I / Io) in Table 3 and in Figure 2:
[0340]
[0341]
[0342]
[0343] Table 3
[0344] Example 6: Reversibility of the use of a copolymer comprising a salt of a residue of formula (I) for the detection of chlorides.
[0345]
[0346] The behavior of the membrane prepared in Example 2 was studied during several cycles of use as a chloride sensor in water with a subsequent washing.
[0347]
[0348] A dense membrane prepared according to Example 2 was die-cut in the form of a disc of 10 mm in diameter, and immersed in 2 ml of distilled water. NaCl was added until reaching a concentration of 100 mM, and the effect on the disappearance of a band in the fluorescence spectrum was measured. Subsequently the membrane was washed with distilled water, and when the chlorides are removed from the system the initial fluorescence of the material is recovered. This use-wash cycle was repeated 6 times. Figure 3 shows the cycles of use-wash, which are translated into decrease and growth respectively of the fluorescence band centered at 440 nm, and which is obtained by exciting the sample at 321 nm.

权利要求:
Claims (15)
[1]
1. METHOD OF OBTAINING A COMPONER COMPRISING A SALT OF A RESULT OF FORMULA (I):

[2]
2. Method of obtaining according to claim 1, wherein one of the groups R ³ , R ⁴ ,
R ⁵ , R 6, R ⁷ , R 8 or R ⁹ is a methoxy group, and the rest of the groups is H.
[3]
3. Method of obtaining according to any of claims 1 or 2, wherein the polymerization of at least two monomers of step (a), wherein at least one of said two monomers is a monomer Z, further comprises monomers X and Y, where the proportion of Z represents between 0.1% to 10% of the total number of monomers and where the ratio of X to Y is from 1: 9 to 9: 1.
[4]
4. Method of obtaining according to claim 3 wherein the ratio of X to Y is 3: 1 and Z represents 1% of the total number of monomers.
[5]
5. Method of obtaining according to any of claims 1 to 4, wherein the monomer Z is a monomer of formula (II):

[6]
6. Method of obtaining according to claim 5, the monomer of formula (II) is
5-bromo-1-pentene or 4-bromo-1-butene.
[7]
7. Method of obtaining according to any of claims 3 to 6 wherein the monomers X and Y are respectively N-vinyl pyrrolidone and 2-hydroxyethyl acrylate.
[8]
8. Copolymer obtainable by the method of obtaining any of claims 1 to 7.
[9]
9. Copolymer comprising a salt of a residue of formula (I):

[10]
10. Use of a copolymer of any of claims 8 or 9, for the detection and / or quantification of anions.
[11]
11. Use according to claim 10, wherein the anions are chlorides.
[12]
12. Use according to claim 11, wherein the detection and / or quantification of chlorides is carried out in industrial waters or for human consumption.
[13]
13. Use according to claim 11, wherein the detection and / or quantification of chlorides is carried out in the sweat.
[14]
14. Use of a copolymer of any of claims 8 or 9, for the detection of a disease independently selected from cystic fibrosis, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis syndrome, hypothyroidism, malnutrition, mauric syndrome, storage disease of glycogen type 1, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency.
[15]
15. Suit comprising a copolymer of any of claims 8 or 9 for the detection of a disease independently selected from cystic fibrosis, untreated adrenal insufficiency, ectodermal dysplasia, familial cholestasis syndrome, hypothyroidism, malnutrition, mauric syndrome, storage disease of type 1 glycogen, mucopolysaccharidosis, nephrogenic insipid diabetes, fucosidosis, nephrosis or glucose 6-phosphate deficiency.

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WO2019002254A1|2019-01-03|

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ES2695246B2|2019-11-21|

引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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ES2525114A1|2013-06-18|2014-12-18|Universidad De Burgos|Colorimetric iron sensor in aqueous and biological media, such as industrial water, wine and blood |CN111864666A|2020-08-07|2020-10-30|上海贝思特管业有限公司|Heat-resistant wear-resistant high-toughness self-positioning PVC pipe|US4897444A|1985-05-31|1990-01-30|The Research Foundation Of The State University Of New York|Immobilized fluorogenic substrates for enzymes; and processes for their preparation|

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CN103992782A|2014-05-14|2014-08-20|华中科技大学|Acidizing corrosion inhibitor and preparation method thereof|

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ES201730844A|ES2695246B2|2017-06-27|2017-06-27|FLUORIMETRIC SENSORS OF ANIONS|ES201730844A| ES2695246B2|2017-06-27|2017-06-27|FLUORIMETRIC SENSORS OF ANIONS|

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PCT/EP2018/067048| WO2019002254A1|2017-06-27|2018-06-26|Fluorescent sensors for anions|