JP2000119291A - Alkoxysilylated boric salt derivative, production and use thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a new compound useful as an anion excluder for a sol-gel sensitive membrane for measuring the ionic activity, excellent in durability, nontoxic and nonirritating to living bodies and suitable as an ion sensitive membrane capable of indwelling in vivo over a long period. SOLUTION: This compound is represented by formula I R1 is a 1-6C alkyl; (x) and (y) are each an integer satisfying 1<=(x)<=3; 1<=(y)<=3 and [(x)+(y)] is 4; R2 is a (substituted)aromatic group; M is a metal ion; and (n) is 1-6}, e.g. sodium [4-(triethoxysilylpropyloxy)phenyl]-triphenylborate. The compound represented by formula I is obtained by reacting a chlorosilane represented by formula II (preferably trichlorosilane) with a boric salt derivative such as a compound represented by formula III in the presence of a catalyst (preferably platinum) in an anhydrous solvent (preferably benzene), distilling off the solvent, then reacting the resultant chlorosilylated boric salt derivative with an anhydrous alcohol (preferably ethanol) and then distilling off the solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an alkoxysilylated borate derivative, a production method and use thereof.
More specifically, the present invention relates to an alkoxysilylated borate derivative, a method for producing the alkoxysilylated borate derivative, and a sol-gel sensitive film for measuring ion activity using the alkoxysilylated borate derivative.

[0002]

2. Description of the Related Art In recent years, measurement and detection of chemical substances by sensors have been performed in various fields. As one of them, the ion activity in the living body varies in various diseases, so the patient's blood (including serum or plasma, etc.) or urine is used as a sample to selectively measure the ion activity. It is very important to do. Conventionally,
As a method for measuring ion activity with high selectivity, measurement methods such as spectroscopy, flame method, colorimetry, and atomic absorption method have been used. However, the above-described method not only requires a large-sized instrument, but also is not a measurement method excellent in simplicity and rapidity. And quick means have been sought. In order to solve such a problem, in addition to selectively measuring the ion activity in a living body, it is simple and,
As a means for quick measurement, ion sensors, for example,
A method using an ion electrode or a method using an ion field effect transistor has been proposed. Here, the ion electrode is an electrode that enables the specific ion activity in the solution to be measured at the membrane potential indicated by the membrane electrode, and is simple and
It is possible to measure the ion activity quickly and selectively, for example, represented by a glass electrode for pH measurement. In addition, the ion field-effect transistor has an ion-sensitive film attached to the field-effect transistor instead of the metal at the gate, and measures the ion activity in the solution as a change in the current flowing through the transistor. It is possible to do.

[0003] An ion sensor is an excellent method in terms of selectivity, simplicity, and rapidity. By using a sensitive membrane containing an ionophore (also called a neutral carrier), an ion sensor can be used to detect ions to be measured. It is known that the selectivity is improved (JP-A-61-50972, JP-A-59-5180, JP-A-60-202875, and JP-A-62-28785).
2-77374). In these techniques, polyvinyl chloride, silicone rubber, polymethyl methacrylate, polyvinyl acetate, paraffin, collodion, or the like is used as a support for holding the ionophore and the anion exclusion agent. These polymers are only to retain the ionophore or anion exclusion agent, and the ionophore or anion exclusion agent is not bound to the support.
In addition, in order to prepare a sensitive membrane holding an ionophore having excellent ion selectivity, it was necessary to improve the moldability by blending an appropriate plasticizer into the above-mentioned resin and the like. Therefore, these sensitive membranes have problems such as leakage of plasticizers and ionophores, and are in vitro.
ro) or semi-disposable use, there is no problem, but not only the durability of the sensor is low, but also if it is used for a long time in vivo (in vivo), the plasticizer or the ionophore is toxic or irritating to the body. Was completely inadequate.

On the other hand, when such a sensor is used for measuring a chemical substance in a living body, the protein permeability and blood cells contained in the specimen are adsorbed on the sensor surface, so that the material permeability of the sensitive membrane is reduced. Therefore, it was impossible to use it for a long time in a living body. As a result of intensive studies on such problems, the inventors have found that there is almost no adsorption of proteins, blood cells, and the like to the sensor surface using a sol-gel body-sensitive membrane (Anal). Chem., Vol. 69 (13),
2379-2383, 1997). However, since the ion-sensitive membrane having the sol-gel body as a matrix is formed by containing an ionophore in the sol-gel matrix, there is a strong possibility that the ionophore and the like leak from the sensitive membrane as described above, and the When used for durability and measurement of ions in a living body, measures against concerns such as poisoning and irritation to the living body due to leakage of ionophore and the like were not always sufficient. Further, in order to effectively measure the cation activity, it was necessary to include an anion eliminator or the like in order to control the influence of the lipophilic anion on the target cation measurement (edited by the Chemical Society of Japan, Experimental Chemistry Course 27, Bioorganic, p. 238, 1992). Generally, a borate derivative is used as the anion exclusion agent. These substances also function as disintegrants for cell tissues, local anesthetic effects by subcutaneous injection, sensitizers for photographic emulsions, catalysts for synthetic resins, etc. There was a similar problem regarding safety and the like.

However, recently, the necessity of long-term monitoring of ion activity in a living body by an ion sensor has been increased due to its clinical usefulness. For the living body,
It has been desired to develop an ion sensor that does not impart poison or irritation. Until now, an alkoxysilylated borate derivative having a functional group useful for a sensitive film or the like has not been known.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel alkoxysilylated borate derivative which solves the above-mentioned various problems. A second object of the present invention is to provide a method for producing the alkoxysilylated borate derivative. Further, a third object of the present invention is to provide a sol-gel sensitive membrane useful for measuring ion activity, which is bound by using a novel alkoxysilylated borate derivative. For more information,
Provided is a novel alkoxysilylated borate derivative which has excellent durability, that is, does not leak an anion exclusion agent or the like. Another object of the present invention is to provide a sol-gel sensitive film in which a plasticizer or an ionophore does not leak by using a binding type as an ionophore to be used in combination. Also,
An object of the present invention is to provide an alkoxysilylated borate derivative which is nontoxic and nonirritating to a living body and is suitable for an ion-sensitive membrane which can be left in the living body for a long period of time.

[0007]

Means for Solving the Problems The present inventors diligently studied the above problems and found a novel borate derivative containing an alkoxysilyl group, and completed the present invention. That is, the present invention includes the following (1) to (6).

(1) The following general formula (I)

[0009]

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Wherein R ¹ is an alkyl group having 1 to 6 carbon atoms, x and y are 1 ≦ x ≦ 3, 1 ≦ y ≦ 3 and x + y =
An integer that satisfies 4. R ² represents an aromatic group or a substituted aromatic group, and M represents a metal ion. N represents an integer of 1 to 6. ) An alkoxysilylated borate derivative represented by the formula:

(2) R ¹ is a CH ₃ — group or C ₂ H ₅ —
Group, R ² is

[0012]

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[0013]

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(Where X represents Cl, Br or F) or

[0015]

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And the alkoxysilylated borate derivative wherein M ⁺ is Na ⁺ or K ⁺ .

(3) The method for producing an alkoxysilylated borate derivative described above, wherein trichlorosilane is reacted with a borate derivative having an unsaturated group.

(4) The following general formula (I)

[0019]

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(Wherein, R ¹ is an alkyl group having 1 to 6 carbon atoms, 1 ≦ x ≦ 3, 1 ≦ y ≦ 3, and an integer satisfying x + y = 4. R ² is an aromatic group. Group, a substituted aromatic group, and M represent a metal ion, and n represents an integer of 1 to 6). The compound is reacted by using an alkoxysilylated borate derivative represented by the following formula: A sol-gel sensitive membrane for measuring ion activity.

(5) A sol-gel sensitive membrane for measuring ionic activity, wherein the matrix component of the sol-gel sensitive membrane is at least one of tetraethoxysilane or diethoxydimethylsilane and the above-mentioned anion exclusion agent is bonded.

(6) The above sol-gel sensitive membrane for measuring ion activity, wherein the ions to be measured are potassium, sodium, lithium, ammonium, cesium, rubidium, strontium, calcium or magnesium.

[0023]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be specifically described below. The novel alkoxysilylated borate derivative of the present invention is an alkoxysilylated borate derivative represented by the following general formula (I).

[0024]

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Wherein R ¹ is an alkyl group having 1 to 6 carbon atoms, x and y are 1 ≦ x ≦ 3, 1 ≦ y ≦ 3 and x +
It is an integer satisfying y = 4. R ² represents an aromatic group or a substituted aromatic group, and M represents a metal ion. n is 1-2
Indicates an integer of 0.

(2) R ¹ is a CH ₃ — group or C ₂ H ₅ —
The group, R ² ,

[0027]

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[0028]

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(Where X represents Cl, Br or F) or

[0030]

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Specific examples of the general formula (I) include those having the following structures.

[0032]

Embedded image (Here, ph represents a phenyl group. The same applies hereinafter.)

[0033]

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[0034]

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[0035]

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[0036]

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[0037]

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Next, a method for producing the compound represented by the formula (I) will be described. The alkoxysilylated borate derivative represented by the above general formula (I) can be obtained by reacting the borate derivative with chlorosilane and then alkoxysilating it. The borate derivative as the raw material functions as an anion exclusion agent and is obtained by a known method through organic synthesis. The borate derivative used as a raw material may have a functional group capable of reacting with chlorosilane. When there is no such functional group, an appropriate functional group may be introduced by a known method. Examples of such a functional group include an alkyl group, a -CO-O- group, a -CO
-NH- group, -O- group, -O-CO-O- group, -CO-
Examples include an ONH- group and a -NH-O-CO-O-NH- group. As the alkyl group, in a broad sense, CH ₂
ＣＨCH- group, CH ₂ ＣC (CH ₃ )-group and the like. A CH ₂ ＣＨCH— group at the end of the raw material borate derivative,
A functional group represented by CH ₂ ＣC (CH ₃ ) — or the like may be introduced (for example, Tetrahedron Lett.,
33, 3032-3034, 1978 and Bull. Chem. Soc. Jpn. , Vol. 55, 20
05-2009, 1982).

The raw material borate derivative and chlorosilane are combined in a suitable anhydrous solvent in the presence of a catalyst to obtain a chlorosilylated borate derivative, and the solvent is distilled off. It can be obtained by reacting a salt derivative with anhydrous alcohol and distilling off the solvent. Examples of the chlorosilane include trichlorosilane, dichlorosilane, and monochlorosilane. Preferably, it is trichlorosilane.

Solvents used for the binding reaction between the chlorosilane and the borate derivative include benzene, tetrahydrofuran, acetone, methyl ethyl ketone, diethyl ketone,
Acetonitrile, dinitrobenzene and the like can be mentioned. Preferably, benzene is used. The solvent is used in an anhydrous state, but when water is present, the Si-Cl bond is hydrolyzed, and the silyl group and the silyl group are further hydrolyzed to a silanol group, which is bonded to a glass or metal container, or May bind siloxane. Examples of the catalyst used include organic peroxides, ultraviolet rays, tertiary amines, phosphines, and platinum, rhodium and palladium transition metal substances. Preferably platinum

Solvents used for the alkoxylation reaction of the chlorosilylated borate derivative include methanol, ethanol, 1- or 2-propanol, 1- or 2-propanol.
-Butanol, 1-, 2- or 3-heptanol,
Examples thereof include 1-, 2- or 3-hexanol.
Preferably, it is ethanol. Finally, the alkoxysilylated borate derivative can be obtained by distilling off the solvent by an operation such as an evaporator. The reflux time is about 0.5 to 30 hours, preferably 5 to 15 hours. The reaction is preferably performed in an atmosphere of an inert gas such as argon. The reaction temperature is preferably low, from -10 ° C to 1 ° C.
0 ° C. The reaction formula is as follows.

[0042]

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The above-mentioned alkoxylated borate derivative is used together with an ionophore in a sensitive membrane for measuring ion activity. Specific examples of the ionophore used in combination include valinomycin, monensin, biscrownether derivatives, bis (monoaza-12-crown-4) derivatives, bismacrocyclic polyetherdiamide derivatives, and alkyl-substituted 14-crown-4 derivatives. Is mentioned. These compounds are introduced with a functional group in the same manner as described above, reacted with trichlorosilane or the like, and then reacted with alcohol to obtain an alkoxysilylated crown ether derivative. There is no particular limitation as long as it selectively responds to the target ion, but those having high ion selectivity are desirable.

The alkoxysilylated borate derivative of the present invention usually reacts with a sol-gel body of a polymer matrix containing tetraethoxysilane or diethoxydimethylsilane as a base used for an ion-sensitive membrane. Used. As a method for preparing a sensitive film obtained by reacting an alkoxysilylated borate derivative with a base polymer, an alkoxysilylated borate derivative of the present invention and a sol-gel body are mixed under a suitable acidic or basic solvent. Then, it can be obtained by casting to a target site. The sol-gel body as the base polymer matrix used in the reaction may be any sol-gel body that can bind to the alkoxysilylated borate derivative of the present invention. Preferably, tetraethoxysilane, diethoxydimethylsilane and the like can be mentioned, and a sol containing either or both.
It is a gel body.

As a solvent used in the reaction, ethanol,
Examples include alcohols such as methanol, propanol and butanol, hydrophilic organic solvents, and aqueous solutions of mixtures thereof. More preferably, it is an aqueous ethanol solution. As a condition for performing the silane coupling reaction, stirring may be performed under acidic or basic conditions, or heating may be performed after casting. Acids used under acidic conditions include hydrochloric acid, sulfuric acid, acetic acid, nitric acid and the like. More preferably, it is hydrochloric acid. Examples of the base used under basic conditions include trialkylamines such as trimethylamine and triethylamine; aromatic amines such as pyridine and aniline; and ammonia. More preferably, it is ammonia. As the time until casting, while the liquid has a viscous property, that is, after adjusting the mixed solution, 0.5 to 50 hours, preferably cast to the target site by 1 to 36 hours Is preferred.

As described above, the alkoxysilylated borate derivative of the present invention binds to the sensitive membrane and acts as an anion eliminator.

Further, the content of the alkoxysilylated crown ether derivative as an ionophore in the sensitive membrane is desirably in the range of 0.1 to 50% by weight, preferably 0.5 to 20% by weight. When the content of the alkoxysilylated crown ether derivative is less than 0.1% by weight, the response is poor, and when the content of the alkoxysilylated crown ether derivative is more than 50% by weight, the effect corresponding thereto is obtained. Because it is uneconomical. Examples of the alkoxysilylated crown ether derivative to be used in combination include a compound having the following structure.

[0048]

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Where R 'is an alkyl group having 1 to 6 carbon atoms, and R''is a-(CH ₂ ) m- group (where m is 1 to 20).
R ′ ″ is a hydrogen atom or a hydrocarbon group having 1 to 4 carbon atoms. X and y are integers satisfying 1 ≦ x ≦ 3, 1 ≦ y ≦ 3, and satisfying x + y = 4. Z represents an integer of 1 to 6.ア ル コ キ シ When the alkoxysilylated borate derivative of the present invention is used as an anion exclusion agent in the sensitive membrane, the content of the compound is 0.1 to 100 mol%, preferably 5 to 50 mol%, based on the ionophore. Is desirable. If the content of the anion eliminator is less than 0.1 mol%, sensitivity and responsiveness decrease, and if it is more than 100 mol%, the ion selectivity decreases, which is not preferable.

The alkoxysilylated borate derivative of the present invention is reacted with a sensitive film containing tetraethoxysilane, diethoxydimethylsilane, or the like, and is cast on a measurement site of a commercially available ion sensor. Can be incorporated into For example, when the ion sensor is an ion electrode, the sensitive membrane solution may be cast on the electrode, and the solvent may be removed under appropriate conditions, for example, by heating, reducing pressure, or the like. Preferably, the solvent may be removed by heating at 40 to 60 ° C. The thickness of the sensitive film of the ion sensor thus obtained is 10 to 500 μm, preferably 50 to 300 μm.

When the ion sensor is an ion field effect transistor, the ion sensitive film is cast in the same manner as that of the ion electrode, instead of the metal of the gate of the field effect transistor. be able to. When an ion sensor is formed using a sensitive film, a structure known in the field of an ion electrode or a field effect transistor can be appropriately employed. For example, an apparatus in which a sensitive film formed by reacting the compound of the present invention with an ion electrode formed of a sol-gel body is schematically shown in FIG. FIG. 5 schematically shows an apparatus in which the compound of the present invention is formed on a field-effect transistor as a sol-gel body of a sensitive film as an anion eliminator.

The ion to be measured depends on the structure of the ionophore to be selected, but the ions are potassium, sodium, lithium, ammonium, cesium,
Rubidium, strontium, calcium or magnesium. In particular, potassium, sodium, ammonium, calcium and magnesium are frequently used in the measurement. As described above, an ionophore corresponding to the ion to be measured is appropriately selected from various crown ether derivatives and reacted in the same manner to obtain an alkoxysilylated compound, and a bond-type sensitive membrane is obtained by using the compound. And various ions can be measured.

An ion activity measuring device is prepared using the sensitive membrane of the present invention, and the electrode manufactured as described above can be immersed in a sample solution to measure the amount of ions as a voltage.

In the present invention, the ionophore is
An organic compound that has the function of transporting ions and refers to a substance that takes in ions. Here, the term includes a crown ether derivative as a raw material and a derivative after silylation. Further, “bond” means a chemical bond, which is fixed to the sensitive membrane. The term “sensitive membrane” means that the target ions can be captured and released when they come near.

[0055]

The borate derivative of the present invention is a novel alkoxysilylated borate derivative. The novel alkoxysilylated borate derivatives of the present invention, when bound, are useful as anion scavengers in bonded sol-gel sensitive membranes. That is, it is a compound suitable for an ion-sensitive membrane that can be bonded to a membrane together with a bonded ionophore for measuring ion activity. Further, the production method of the present invention can easily obtain an alkoxysilylated borate derivative having a functional group. The sensitive membrane formed by binding the alkoxysilylated borate derivative of the present invention is nontoxic and non-irritating to living organisms because an anion eliminator for measuring ion activity is bound to the membrane together with the ionophore. Because of its chemical properties and chemical bonding, it has excellent durability and can be used for a long period of time. Therefore, the sensitive membrane reacted with the borate derivative of the present invention has excellent durability as described above, and can be used for a long period of time. it can.

[0056]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail based on embodiments. 1. Production of alkoxysilylated borate derivative The alkoxysilylated borate derivative according to the present invention and physical properties will be described. However, the borate derivative used as a raw material was synthesized according to a known method. The synthesis examples and physical properties of the alkoxysilylated crown ether derivative having a function as an ionophore are also shown.

Example 1 Alkoxysilylated borate derivative
Synthesis of the conductor 4-bromophenyl in 30 ml of tetrahydrofuran
Ether, 40 mmol and magnesium ribbon, 40 m
and 4-allyloxyphenyl-mag
Nesium bromide was prepared. This solution is triphenyl
Borate, dichloromethane solution containing 40 mmol, 3
Then, the mixture was stirred at room temperature for 3 hours. Evaporate the solvent
After that, 50 ml of a saturated sodium chloride solution was added to the residue.
After dissolving, extract three times with 30 ml of dichloromethane.
Was. Collect the dichloromethane extract, evaporate the solvent and extract
I got something. Recrystallize with xylene and extract
Thorium (4-allyloxyphenyl) triphenylbo
Rate crystals were obtained. Melting point, ¹H-NMR, IR, mass
The physical properties measured by the analysis are shown below. Melting point measurement; mp. 260 ° C (decomposition temperature)¹ H-NMR analysis results;¹ H-NMR ｛δ (ppm), CDCl_ThreeMedium, 270 MH
z, TMS｝ 6.0-6.2 (1H, m, CH_Two= CH), 4.59
(2H, d, J = 5.1 Hz, CHCH _TwoO) 5.3
−5.5 (2H, m, CH _Two= CH), 6.6-6.7.
(19H, m, aromatic H) Results of IR analysis; IR (cm^-1); 3060,3000,1640,15
80, 1480, 1185, 745 Results of mass spectrometry; Mass (m / z [% rel intensity])
= 398 (M⁺, 10), 153 (100) From the above results, it was confirmed that the compound had the following structure.
I accepted.

[0058]

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Here, the ph group represents a phenyl group.

1.2 mmol of sodium (4-allyloxyphenyl) triphenylborate obtained above and 1.48 mmol of trichlorosilane were added to anhydrous benzene,
Dissolve in 30 ml and add hexachloroplatinic acid monohydrate, 1
A 0 mg-tetrahydrofuran solution (2 ml) was added, and the mixture was stirred under an argon atmosphere and heated under reflux for 10 hours. After distilling off benzene, 50 ml of absolute ethanol was added to the residue, and the mixture was stirred under ice cooling. The ethanol containing the catalyst was removed by collecting the precipitate by centrifugation, and excess ethanol was distilled off. As a result, sodium [4-
(Triethoxysilylpropyloxy) phenyl] -triphenylborate (abbreviated as BAS-1) was obtained as a viscous liquid (yield 91%). ^The physical properties measured by ¹ H-NMR and IR are shown below. ¹ H-NMR analysis results; ¹ H-NMR ｛δ (ppm), 270 MH in CDCl ₃
z, TMS} 0.81 (2H, t, J = 7.6Hz, SiC H 2),
1.24 (9H, t, J = 7.3Hz, CH 2 C H 3),
3.73 (6H, q, J = 6.8Hz, C H 2 CH 3),
_{4.3-4.5 (4H, m, SiCH 2} (C H 2) 2),
7.4-7.8 (19H, m, aromatic H) Results of IR analysis; IR (cm ^-1 ); 2930, 2860, 1585, 14
80, 1415, 1190, 1075, 740. From the above results, it was confirmed that the compound had the following structure.

[0061]

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Here, the ph group represents a phenyl group.

Synthesis Example 1 bis (12-crown-4)-
Production of Alkoxysilyl Derivative In the general formula (II), R ¹ ＝ CH ₃ CH ₂ —, R ² = −
_{(CH 2) 3 -, R} 3 = CH 3 -, x = 3, y = 1 and z
= 2 bis (12-crown-4) -triethoxysilyl derivative was synthesized as follows. Hydroxyethyl-
12-Crown-4 is described in Anal. Chem. , 64th
2508-2511, 1992. Prepared according to the method described in Hydroxyethyl-12-crown-4, 90 mmol and 2-allyl-2-methylmalonyl chloride (40 mmol) were converted to anhydrous benzene, 60 m
and 20 g of silver cyanide was added thereto to form a suspension. The mixture was refluxed and heated for 7 days while stirring. After the reaction, silver cyanide was separated by filtration, and the filtrate was passed through a celite column. After elution with benzene, benzene was distilled off from the recovered solution. The residue was dissolved in chloroform and further purified by gel filtration. As a result, bis [(12-crown-4-) ylmethyl] -2-allyl-2-methylmalonate was obtained as a viscous liquid (yield 30%). ¹ H
-Physical properties measured by NMR, IR and mass spectrometry are shown below. ¹ H-NMR analysis results ^{of; 1 H-NMR {δ (} ppm), in CDCl _3, 270MH
z, TMS} 1.40 (3H, s, C H 3), 2.60 (3H, d,
_{J = 7.6Hz, C H 2 C} ), 3.5-3.8 (30
_{H, m, C H 2 OC} H 2, OC H), 4.1-4.3 (4
_{H, m, COOC H 2)} , 5.0-5.1 (2H, m,
_{C H 2 = CH), 5.6-5.8} (1H, m, CH 2 = C
H ) IR analysis result; IR (cm ^-1 ); 2910, 2860, 1730, 16
50, 1240 Results of mass spectrometry; MS (m / z [% rel. Inten
situation]) = 535 (M ⁺ , 100)

Bis [12-crown-4-) methyl]
1.2 mmol of 2-allyl-2-malonate and 1.48 mmol of trichlorosilane in anhydrous benzene, 30 m
l, hexachloroplatinic acid monohydrate, 10mg
-2 ml of a tetrahydrofuran solution was added, and the mixture was stirred under an argon atmosphere and heated under reflux for 10 hours. After distilling off benzene, 50 ml of absolute ethanol was added to the residue, and the mixture was stirred under ice cooling. The ethanol containing the catalyst was removed by collecting the precipitate by centrifugation, and excess ethanol was distilled off. As a result, bis [12-crown-4-) methyl] -2-triethoxypropylmethyl malonate (abbreviated as CAS-1) was obtained as a viscous liquid (yield 91%). ^The physical properties measured by ¹ H-NMR and IR are shown below. ¹ H-NMR analysis results ^{of; 1 H-NMR {δ (} ppm), in CDCl _3, 270MH
z} 0.10 (2H, t, J = 7.6Hz, SiC H 2),
1.21 (9H, t, J = 6.5Hz, CH 2 C H 3),
_{1.42 (3H, s, CH 2} CC H 3), 1.6-1.9
_{(4H, m, SiCH 2 (} C H 2) 2 OC), 3.4-
3.9 (36H, m, SiOC H 2, C H 2 OC H 2, O
C H ), 4.1-4.3 (4H, m, COOC H ₂ ) IR analysis results; IR (cm ⁻¹ ); 2960, 2870, 1730, 12
60, 1100, 805 From the above results, it was confirmed that the compound had the following structure.

[0065]

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2. Production of an ion sensor equipped with an ion-sensitive membrane Reference example 1; Production of a field-effect transistor equipped with a BAS-1 binding sol-gel sensitive membrane Field-effect transistor (Shindengen El)
electric Inc. ) Gate (10 μm × 37)
0 μm), 1 μl of a 1% poly (3-octylthiophene) -chloroform solution was cast, and dried under reduced pressure.
A poly (3-octylthiophene) layer of about 10 μm was formed on the gate of the field effect transistor. continue,
Tetraethoxysilane, 0.0012 mol, diethoxydimethylsilane, 0.0035 mol, ethanol,
A solution was prepared by mixing 69 μl, 0.1 mol / L hydrochloric acid (21 μl), 0.2 mg of BAS-1 prepared in Example 1 and 1 mg of CAS-1 prepared in Synthesis Example 1, and 1 μl of this mixture was prepared. Was cast on the gate of a field-effect transistor having a poly (3-octylthiophene) layer formed thereon. After heating and drying at 50 ° C. for 2 days, a BAS-1 bonded sol-gel sensitive film-mounted field effect transistor (Na ⁺⁾ having a thickness of about 150-200 μm on the gate portion.
-ISFETs-1).

3. Evaluation as ion sensor Reference Example 2: Preparation of calibration curve based on ion activity and potential difference between electrodes Field-effect transistor prepared in Reference Example 1, Na ⁺ −
After conditioning the ISFETs-1 is immersed for 12 hours in the sodium chloride solution of 3 mol / L, were prepared calibration curve by the activity of sodium ions in the sample solution [a] Na ⁺ and the potential difference between the electrodes (E / mV) . The measurement was performed using a field effect type pH / mV meter (Shindeng).
en Electric Inc. ) At 25 ° C. As a reference electrode, a double-junction type electrode having an inner solution of 3 mol / L potassium chloride and an outer solution of 1 mol / L lithium acetate was used. As a result, as shown in FIG. 1, the calibration curve showed sodium ion activity [a] Na
⁺ Showed linearity in a wide range of 3 × 10 ^{−5 to 1} M, and showed a response by Nernst.

Reference Example 3 Durability Test The field-effect transistor prepared in Reference Example 1, Na ⁺ −
ISFETs-1 was continuously immersed in the sample solution for 100 days, and the potential difference between the electrodes (E / mV) of the sample solution was measured. In addition,
The experimental conditions were the same as in Reference Example 2. The result is shown in FIG. (Black circle in the figure)

Comparative Reference Example 1 CAS-1 was converted to bis [(12-crown-4-) ylmethyl] -2-allyl-2-methylmalonate, BAS-1
Was changed to sodium (4-allyloxyphenyl) triphenyl borate to prepare an ionophore-containing sol-gel sensitive membrane solution in accordance with Reference Example 1. Sol-
A sol-gel sensitive film-mounted field effect transistor containing sodium (4-allyloxyphenyl) triphenyl borate was prepared in the same manner as in Reference Example 1 except that the gel-sensitive film solution was used. Was carried out.
The results are also shown in FIG. (White circle in the figure)

The horizontal axis in FIG. 2 is time (days), and the vertical axis is a potential change (slope / mV dacade) with respect to a change in ion activity, which is an index indicating the degree of deterioration of the performance of the ion sensor.
^-1 ). As shown here, the sol-gel sensitive film-mounted field effect transistor of the present invention, which is a compound of the present invention, showed no deterioration in performance during the measurement period (100 days). In the case of the field-effect transistor equipped with the sol-gel sensitive film containing the compound, the performance deteriorated in about 30 days.

As described above, according to the sol-gel sensitive membrane of the present invention for measuring the ion activity, the anion eliminator and the ionophore are combined, so that the durability is excellent. Further, it is possible to provide an ion activity measuring device which is non-irritating to a living body and can be kept in the living body for a long period of time.

FIG. 4 shows a schematic diagram in which the compound of the present invention was bound to a sensitive membrane and used for an ion electrode. Reference Example 1
FIG. 5 shows a schematic diagram used for the field effect transistor of FIG.

[Brief description of the drawings]

FIG. 1 is a graph illustrating a calibration curve of a sodium ion field effect transistor using a sensitive film obtained by reacting an alkoxysilylated borate derivative and an alkoxysilylated crown ether derivative of the present invention.

FIG. 2 is a diagram of a repetition test result of a sodium ion field effect transistor using a sensitive film (black circles) and the case of Comparative Reference Example 1 (white circles).

FIG. 3 is a cross-sectional view showing an example of an electrode configuration using the compound of the present invention bonded to a sensitive film.

FIG. 4 is a schematic cross-sectional view of the structure of ISFETs of an ion activity measurement device for a field-effect transistor using the compound of the present invention bonded to a sensitive film.

[Explanation of symbols]

 1. Sensitive film 2. 2. Reference electrode Sample solution 4. Internal liquid 5. Internal pole 6. 6. Liquid junction solution Shiohashi 8. Gate 9. Polythiophene film 10. Channel 11. Drain voltage 12. Gate current 13. Gate voltage

Continued on the front page F term (reference) 4H048 AA01 AA02 AA03 AB80 AC90 VA00 VA11 VA20 VA75 VB10 4H049 VN01 VP01 VQ19 VQ97 VR20 VR40 VU31 VW02 4H050 AA01 AA02 AA03 AB20

Claims (6)

[Claims] (1) The following general formula (I): (Wherein, R ¹ is an alkyl group having 1 to 6 carbon atoms, x and y are
It is an integer satisfying 1 ≦ x ≦ 3, 1 ≦ y ≦ 3, and satisfying x + y = 4. R ² represents an aromatic group or a substituted aromatic group, and M represents a metal ion. N represents an integer of 1 to 6. ) An alkoxysilylated borate derivative represented by the formula: Wherein R ¹ is, CH ₃ - group, or a C ₂ H ₅ - group, R ²
Is , (Where X represents Cl, Br or F) or The alkoxysilylated borate derivative according to claim 1, wherein M ⁺ is Na ⁺ or K ⁺ . 3. The method for producing an alkoxysilylated borate derivative according to claim 1, wherein trichlorosilane is reacted with a borate derivative having an unsaturated group. 4. A compound represented by the following general formula (I): (Wherein, R ¹ is an alkyl group having 1 to 6 carbon atoms, x and y are
It is an integer satisfying 1 ≦ x ≦ 3, 1 ≦ y ≦ 3, and satisfying x + y = 4. R ² represents an aromatic group, a substituted aromatic group, M
Represents a metal ion. N represents an integer of 1 to 6. )
A sol-gel sensitive membrane for measuring ion activity, which comprises using an alkoxysilylated borate derivative represented by the formula (1) as an anion exclusion agent and reacting the alkoxysilylated borate derivative. 5. The method according to claim 1, wherein the matrix component of the sol-gel sensitive film is
A sol-gel sensitive membrane for measuring ion activity, comprising the anion scavenger according to claim 4 bonded to at least one of tetraethoxysilane and diethoxydimethylsilane. 6. The sol according to claim 4, wherein the ion to be measured is potassium, sodium, lithium, ammonium, cesium, rubidium, strontium, calcium or magnesium.
Gel sensitive membrane.