JPH06279465A - Metal complex - Google Patents

Abstract

PURPOSE:To obtain a metal complex which is prepared by allowing silver ion to chelate with specific ligands and has a color from nothing to light yellow, resistant to photodecomposition, bondable to surfaces of glass or the like with high durability, thus useful as an antimicrobial agent. CONSTITUTION:A compound of formula I [X is N-containing heterocyclic ring; Y is NH, N(CH3); Z is NO3, ClO4, CH3COO; R, R' are lower alkyl; (a) is integer of 0 to 2; (b) is 0 or 1 (integer); (c) is 1 to 3 (integer); (d) is 1 to 3, respectively]. For example, silver ion complexes a ligand of formula II to give the objective complex of formula I.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel metal complex useful as an antibacterial agent or an antibacterial treating agent.

[0002]

2. Description of the Related Art Conventionally, silver ions have attracted attention as an antibacterial agent against various bacteria and molds because they have a broad antibacterial spectrum and low toxicity. In order to effectively utilize the antibacterial property of silver ions, particles of silver ion-containing zeolite, glass, apatite, etc. are known as those that effectively elute silver ions. The silver ions in these particles are fixed by ion exchange or dispersed in glass, and the silver ions are contained even inside the particles.

On the other hand, as compounds containing antibacterial silver ions, silver salts such as silver nitrate, silver perchlorate and silver nitrite,
Alternatively, a diammine silver complex, a bispyridine silver complex, 1,
Complexes such as a 10-phenanthroline silver complex and an ethylenebisbiguanide silver complex are known.

[0004]

However, these compounds are easily decomposed by light, so that glass, ceramics,
It does not have the function of chemically bonding to substrates such as paper and plastic. Therefore, when these compounds are used as antibacterial treatment agents, most of the complexes are dissolved in a short time when they are brought into contact with a solvent, so that the effect is not sustainable, and therefore, the durability is insufficient, and other problems occur. Yes, it is not suitable as an antibacterial treatment agent.

[0005]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a metal complex in which a ligand having an alkoxysilyl group and a nitrogen-containing heterocycle is coordinated with silver ion, They have found that they are suitable for antibacterial agents such as particles, and completed the present invention.

That is, the present invention has the general formula

[0007]

[Chemical 2]

(However, X is a nitrogen-containing heterocyclic group, and Y is NH.
Or N (CH ₃ ) group, Z is NO ₃ , ClO ₄ or CH ₃
COO, R and R'are lower alkyl groups, a is an integer of 0 to 2, b is an integer of 0 or 1, c is an integer of 1 to 3, d is 1
To 3 each represent an integer of 3).

The above metal complex of the present invention (hereinafter referred to as a silver complex) is a metal complex in which a compound represented by the following general formula (2) (hereinafter referred to as a ligand) is coordinated to silver ion.

[0010]

[Chemical 3]

(However, X is a nitrogen-containing heterocyclic group, and Y is NH.
Or an N (CH ₃ ) group, R and R ′ are lower alkyl groups,
a is an integer of 0 to 2, b is an integer of 0 or 1, and c is 1 to 3.
, And d is an integer of 1 to 3).

One of the features of this ligand is that it has an alkoxysilyl group and a nitrogen-containing heterocyclic group.

The alkoxysilyl group of the ligand has the general formula
It is represented by Si (OR) _d R ′ _(3-d) and is one in which at least one alkoxy group is bonded to silicon. General formula O
The alkoxy group represented by R is a lower alkoxy group such as a methoxy group and an ethoxy group. The alkoxysilyl group has 1 or 2 lower alkyl groups represented by the general formula R ′ such as a methyl group and an ethyl group.

On the other hand, the nitrogen-containing heterocyclic group represented by X of the ligand contains a nitrogen capable of coordinating at least one silver ion as a ring-constituting element, and has a 5- or 6-membered ring. And aromatic derivatives thereof, and also includes derivatives thereof.

The following are typical examples of the nitrogen-containing heterocyclic group used in the present invention.

The 5-membered ring and its derivative group are groups derived from oxazole, imidazole, pyrazole, furazan and triazole compounds, and the 6-membered ring and its derivative group are pyridine, pyrimidine, acridine,
Examples include groups derived from pyrazine, pyridazine, phenanthroline, triazine, bipyridine, quinoline, and purine compounds.

[0017] and the nitrogen-containing heterocyclic group - (CH _{2) a} chromatography _{(Y) b - (CH 2} ) c -Si (OR) d R '(3 _{over d)} The group, nitrogen-containing heterocyclic group Are bonded via carbon or nitrogen. When the above-mentioned bond is through the nitrogen in the nitrogen-containing heterocyclic group, the nitrogen in the nitrogen-containing heterocyclic group used for the bond has a low coordination ability to silver ions, and therefore, in the nitrogen-containing heterocyclic group. Requires at least two nitrogens.

Specific examples of the ligand contained in the metal complex of the present invention include the following ligands.

[0019]

[Chemical 4]

[0020]

[Chemical 5]

[0021]

[Chemical 6]

As the ligand represented by the general formula (2), a commercially available one can be used, but it can also be synthesized by a known method.

For example, a method for synthesizing 2- (trimethoxysilyl) ethyl-2-pyridine by reacting 2- (trichlorosilyl) ethyl-2-pyridine produced by the reaction of 2-vinylpyridine and trichlorosilane with methyl orthoformate, or , Trimethoxysilane and 2
-Addition reaction such as a method of synthesizing 2- (trimethoxysilyl) ethyl-2-pyridine by reaction with -vinylpyridine. Also, German Patent 2,420,
801 to ethyl orthoformate as described in 801.
Another is a ring closure reaction in which N- [3- (triethoxysilyl) propyl] -4,5-dihydroimidazole is synthesized by reacting-(2-aminoethyl) -3-aminopropyltriethoxysilane.

In the present invention, the metal complex represented by the general formula (1) is a metal complex in which the above-mentioned ligand is coordinated with silver ion. The metal complex is composed of a complex ion in which two molecules of the above ligand are coordinated with one silver ion and an anion represented by the general formula Z as a counter ion thereof. The _{^{anion, NO 3 -, ClO 4 -}} , or CH a ₃ COO ^{chromatography.} Those which react with silver ions to form stable salts such as silver chloride, such as chloride ions, are not included.

The production method of the metal complex of the present invention is not particularly limited, but the simplest production method can be selected and adopted depending on the combination of the above-mentioned ligand and the silver compound serving as the supply source of silver ions.

For example, in a solution in which a silver compound is dissolved,
Examples include a method of producing the metal complex of the present invention by adding the ligand or a solution in which the ligand is dissolved, and a catalyst as required.

As the silver compound, a silver compound which can react with the ligand used in the present invention can be used without limitation. Specific examples include silver nitrate, silver nitrite, silver perchlorate, and silver acetate.

As the catalyst, known catalysts such as acids, alkalis and activated carbon can be used.

Further, the solvent used in the production of the metal complex of the present invention is one which dissolves the above-mentioned silver compound and / or ligand and does not easily hydrolyze the alkoxysilyl group contained in the ligand. Any known solvent can be used without limitation. As such a solvent, for example, alcohols such as methanol, ethanol, and isopropanol,
There are hydrocarbons such as benzene, toluene, xylene, hexane, butane, and cyclohexane, ethers such as diethyl ether and ethyl methyl ether, ketones such as acetone, acetylacetone, ethyl methyl ketone, acetonitrile, dioxane, etc. Alternatively, they can be mixed and used.

The ratio (molar ratio) of the charged amounts of the silver compound and the ligand is adjusted according to the kind of metal complex to be produced.
Since two ligands are coordinated with one silver ion, at least 2 moles or more of the ligand is required for 1 mole of the silver compound having one silver ion. 2 to 5 times the molar amount of ligand is used.

The concentration of the silver compound and the ligand in the solvent for producing the metal complex of the present invention is not particularly limited,
It may be appropriately determined in consideration of the solubility of the silver compound and the ligand. The temperature and time required for the reaction of the silver compound and the ligand are not particularly limited, and usually from room temperature to 100.
It is carried out in the temperature range of ° C for several minutes to several hours. The reaction time can be shortened by heating.

The metal complex obtained by the above reaction is
If necessary, it is purified by a molecular sieve column, recrystallization, extraction and the like.

The metal complex of the present invention is usually a colorless or yellow viscous substance and is soluble in a solvent. However, since it has an alkoxysilyl group, it can be easily heated or heated with an acid, an alkali, water or the like. Polycondensates to become insoluble. Further, the alkoxysilyl group of the metal complex of the present invention easily chemically bonds to the surface of a substance having a hydroxyl group such as ceramics, glass and paper. Furthermore, antibacterial glass, gel, or particles can be synthesized by utilizing a polycondensation reaction with another alkoxysilane compound or a metal alkoxide compound.

For example, when the metal complex of the present invention is mixed with a partial hydrolyzate of tetraethyl silicate, a condensate of both compounds is formed. By hydrolyzing the condensate in an alkaline alcohol, silica-based particles containing a metal complex can be produced. Further, by gradually hydrolyzing the condensate to prepare a bulk body, an antibacterial gel or glass can be obtained.

The metal complex of the present invention comprises a complex ion in which a heterocycle-containing alkoxylane compound is coordinated with silver ion and an anion as a counter ion thereof, and can be determined by a general chemical analysis means. For example, infrared absorption spectrum, visible and ultraviolet absorption spectrum, nuclear magnetic resonance spectrum, atomic absorption spectrum, inductively coupled plasma emission spectrum (hereinafter referred to as ICP), elemental analysis, thermal analysis, ion chromatographic analysis, mass spectrometry and the like.

The composition ratio of silver, ligand and anion in the metal complex is determined by the following method. The contents of silver and silicon in the metal complex are revealed by analysis of silver and silicon by atomic absorption spectrometry or ICP analysis. The content of the ligand is determined by elemental analysis of the metal complex or analysis of silicon by ICP, infrared spectrum, nuclear magnetic resonance spectrum,
It is determined by mass spectrometry or the like. Further, the content rate of anions is clarified by electrophoretic analysis, ion chromatographic analysis, elemental analysis and the like.

In the metal complex of the present invention, the coordination of the ligand to the silver ion is caused by the shift of the peak identified by nitrogen in the heterocycle in the infrared absorption spectrum, or in the nuclear magnetic resonance spectrum. It can be confirmed by the shift of the peak of proton or carbon in the product, or by the appearance of a new absorption band which is not found in the silver compound or the ligand used as a raw material in the visible or ultraviolet absorption spectrum. Also, the chemical structure of the ligand in the metal complex is revealed by an infrared spectrum or a nuclear magnetic resonance spectrum.

The metal complex of the present invention is a useful substance as an antibacterial agent or a catalyst.

[0039]

INDUSTRIAL APPLICABILITY The metal complex of the present invention exhibits antibacterial properties because it appropriately dissociates silver ions. Furthermore, it is colorless or pale yellow, does not easily decompose by light, and has an alkoxysilyl group at the end, and therefore can be chemically bonded to the surface of glass or ceramics. Therefore, it is useful as an antibacterial treatment agent having excellent light stability and durability.

[0040]

EXAMPLES Next, the present invention will be described more specifically by way of examples, but the present invention is not limited to the following examples.

In the following examples, TMSEPYD is 2
-(Trimethoxysilyl) ethyl-2-pyridine
ESPIMD represents N- [3- (triethoxysilyl) propyl] 4,5-dihydroimidazole, respectively.

Example 1 To a solution prepared by dissolving 0.187 g of silver nitrate (manufactured by Wako Pure Chemical Industries, Ltd.) in 20 ml of methanol, a solution prepared by dissolving 0.5 g of TMSEPYD (manufactured by Chisso Corp.) in 5 ml of methanol was added and mixed. The solvent was removed by a rotary evaporator to obtain a viscous and benzene-soluble pale yellow compound.

From the results of ICP analysis (inductively coupled plasma emission spectroscopic analyzer, SPS1200A, manufactured by Seiko Denshi Kogyo), this compound was found to contain Ag of 17.2% by weight and Si9.
9. 0% by weight was analyzed from the result of electrophoresis ion analysis (capillary tube type isotachophoresis analyzer, IP-3A, manufactured by Shimadzu Corporation).
It was found to contain 9% by weight of NO ₃ , respectively. Further, each peak of the ¹³ C-NMR spectrum of this compound was shifted as shown in Table 1 as compared with that of TMSEPYD not coordinated with silver ion. The chemical shift showing the position of each peak in Table 1 was determined on the basis of 206.5 ppm which is the chemical shift (long range multiplet line) of (CD ₃ ) ₂ CO used as the solvent of the measurement sample.

From the above analysis results, the obtained compound is
Nitrogen in the pyridine ring coordinates to the silver ion, [Ag (TM
It was found to be a metal complex having a chemical structure of SEPYD) ₂ ] NO ₃ .

Example 2 To a solution prepared by dissolving 0.187 g of silver nitrate (manufactured by Wako Pure Chemical Industries, Ltd.) in 20 ml of methanol, a solution prepared by dissolving 0.6 g of TESPIMD (manufactured by Chisso Corp.) in 5 ml of methanol was added and mixed. The solvent was removed by a rotary evaporator to obtain a pale yellow viscous liquid soluble in benzene. This compound was analyzed by ICP analysis (inductively coupled plasma optical emission spectrophotometer, SPS1200A, manufactured by Seiko Denshi Kogyo Co., Ltd.) to determine Ag 15.0 wt% and Si 7.8 wt% by electrophoretic ion analysis (capillary capillary isotachophoresis analysis). Device, IP-3
8.6 wt% NO from the results of A, Shimadzu Corporation)
It turns out that each contains ₃ . Furthermore, each peak of the ¹³ C-NMR spectrum of this compound was shifted as shown in Table 1 as compared with that of TESPIMD not coordinated to the metal. The chemical shift showing the peak position of the ¹³ C-NMR spectrum in Table 1 was determined on the basis of 206.5 ppm which is the chemical shift (long range multiplet line) of (CD ₃ ) ₂ CO used in the solvent of the measurement sample.

In addition, among the two nitrogen atoms in the imidazole ring, the nitrogen atoms bonded to three carbon atoms have a much lower coordination capacity for metal ions than the nitrogen atoms bonded to two carbon atoms. Therefore, the nitrogen coordinated to the silver ion is nitrogen bonded to two carbons and bonded to the carbons via a double bond.

From the above results, the obtained compound is a metal complex having a chemical structure of [Ag (TESPIMD) ₂ ] NO ₃ in which nitrogen bonded to two carbons in the imidazole ring is coordinated with silver ion. I knew it was.

[0048]

[Table 1]

Example 3 To a solution prepared by dissolving 0.228 g of silver perchlorate (manufactured by Wako Pure Chemical Industries, Ltd.) in 20 ml of methanol was added a solution prepared by dissolving 0.5 g of TMSEPYD (manufactured by Chisso Corp.) in 5 ml of methanol. Mixed. The solvent was removed by a rotary evaporator to obtain a viscous and benzene-soluble pale yellow compound.

From the result of ICP analysis (inductively coupled plasma emission spectroscopic analyzer, SPS1200A, manufactured by Seiko Denshi Kogyo), this compound was found to have Ag of 16.3% by weight and Si8.
5% by weight was determined from the result of electrophoretic ion analysis (capillary tube type isotachophoresis analyzer, IP-3A, manufactured by Shimadzu Corporation) to be 1
It was found to each contain 5.0% by weight of ClO ₄ .

Furthermore, each peak of the ¹³ C-NMR spectrum of this compound is TMSEP not coordinated with silver ion.
Compared to that of YD, the shift was as shown in Table 2. The chemical shift showing the position of each peak in Table 2 was determined based on 206.5 ppm which is the chemical shift (long range multiplet line) of (CD ₃ ) ₂ CO used in the solvent of the measurement sample.

From the above analysis results, the obtained compound was
Nitrogen in the pyridine ring coordinates to the silver ion, [Ag (TM
It was found to be a metal complex having a chemical structure of SEPYD) ₂ ] ClO ₄ .

[0053]

[Table 2]

Application Example 1 1 g of the metal complex synthesized in Example 1 was dissolved in a mixed solvent of 49 ml of methanol and 1 ml of water to prepare a metal complex-containing solution.

25 ml of the metal complex-containing solution had a particle size of 1.
Disperse 1 g of 7 μm silica particles and stir at room temperature for 20 minutes. After filtration with 5C filter paper, washing with methanol, drying at room temperature for 24 hours, and further drying at 80 ° C for 1 hour to prepare treated particles. The antibacterial property of the treated particles was determined by the halo test shown below.

The halo test is a method of sticking a test piece on a plate agar medium and measuring the width of the inhibition zone after culturing. The method for preparing the medium is as follows. Bacto-pepton1
The pH of a solution prepared by dissolving 0 g, Beaf Extract 5 g, and sodium chloride 5 g in 1 liter of distilled water was adjusted to 6.8 with 2N NaOH to prepare a culture solution. This culture solution 10m
1 is dispensed into a test tube (12.5 x 17 mm), and 120
Sterilized at 20 ° C. and 1 atm for 20 minutes. The strain was transplanted to this and cultured at 37 ° C. for 24 hours to prepare a bacterial solution. After adding 1.5 w% agar to the culture solution prepared above, it was sufficiently dissolved. Next, 120 ° C, 1 atm
And sterilized for 20 minutes. After cooling it to 45 ° C,
1 ml of the bacterial solution was inoculated into the cooled solution to prepare a bacterial inoculated agar culture solution. The agar culture solution inoculated with the bacteria was added to a plate (21 x 1
5 cm) was dispensed to prepare a bacterial inoculation agar medium. The test sample was gently pressed against and adhered to the agar inoculated agar medium. The thus-prepared test sample-attached bacterial inoculated agar medium was cultured at 37 ° C. for 24 hours. Then, the width of the inhibition zone around the test piece was measured from the back through the bottom of the plate medium. The width of the inhibition zone showing the antibacterial property of the test sample is obtained by the following formula. The presence of the prohibited zone indicates that the subject has antibacterial properties.

Two types of bacteria were used in this test, Staphylococcus aureus and Bacillus subtilis. The result of the test using Staphylococcus aureus is shown in A, and the result of using Bacillus subtilis is shown in B.

W = (T−D) / 2; W = width of inhibition zone (mm) T = diameter of inhibition zone including test (mm) D = diameter of test piece (mm) tableting using treated particles Pressure of 200 Kg with a machine,
A test piece having a diameter of 10 mm and a thickness of 1 mm was prepared, and the antibacterial property was examined by a hello test. As a result, it was found that the treated particles had a stop band width of 3.5 mm for both A and B, and exhibited sufficient antibacterial properties.

Application Example 2 With respect to the metal complex synthesized in Example 2, treated particles and test pieces for evaluating antibacterial properties were prepared in the same manner as in Application Example 1.
When the antibacterial property evaluation of this test piece was examined by a halo test, it was found that the width of the inhibition zone was 3.5 mm for both A and B, and the treated particles exhibited sufficient antibacterial property.

Claims (1)

[Claims] 1. A general formula: (However, X is a nitrogen-containing heterocyclic group, Y is NH or N (C
H ₃₎ group, Z is NO _3, ClO ₄ or CH ₃ COO, R and R 'is a lower alkyl group, a is an integer of 0 to 2, b is an integer of 0 or 1, c is an integer of 1 to 3, d represents an integer of 1 to 3, respectively).