Onium-Functionalized Siloxanes

Abstract

The present invention relates to an onium-functionalized siloxane having the general Formula (X) or (X-A) as defined herein; a method for preparing the onium-functionalized siloxane; and its use as an antimicrobial agent.

Claims

1. An onium-functionalized siloxane having the general Formula (X) or (X-A) ##STR00011## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 may be the same or different and each is independently selected from a hydrogen atom or a linear, branched or cyclic hydrocarbon residue having 1 to 20 carbon atoms which may contain at least one heteroatom; A is a heteroatom; Z is selected from a linear, branched or cyclic hydrocarbon residue having 2 to 60 carbon atoms which may contain at least one heteroatom; Y is an onium group; X is selected from halogen atoms, pseudohalogens, or anions selected from Tf.sub.2N, BF.sub.4 or PF.sub.6; in Formula (X) n1 is an integer from 1 to 1000, n2 is an integer from 0 to 100, and p is an integer from 0 to 1000; and in Formula (X-A) n1 is an integer from 1 to 100, n2 is an integer from 0 to 10, and p is an integer from 0 to 100, wherein the sum p+n1+n2 is equal to or higher than 3.

2. The onium-functionalized siloxane according to claim 1, wherein A is O or S or NR.sup.7 or PR.sup.7, where R.sup.7 is selected from a hydrogen atom, a C.sub.1-C.sub.8 alkyl group, a C.sub.3-C.sub.10 cycloalkyl group, a C.sub.6-C.sub.18 aryl group or a C.sub.6-C.sub.18 aralkyl group, which may contain at least one heteroatom.

3. The onium-functionalized siloxane according to claim 1, wherein the onium-functionalized siloxane is a monomer, oligomer or polymer and has a number average molecular weight (Mn) of from 100 to 50,000 g/mol.

4. The onium-functionalized siloxane according to claim 1, wherein Y is an onium group, which is represented as ER.sup.cR.sup.d where E is a positively charged atom selected from the 16th group of the periodic table or ER.sup.cR.sup.dR.sup.e where E is a positively charged atom selected from the 15th group of the periodic table, wherein R.sup.c, R.sup.d and R.sup.e may be the same or different and each is independently selected from a hydrogen atom, a C.sub.1-C.sub.8 alkyl group, a C.sub.3-C.sub.10 cycloalkyl group, a C.sub.6-C.sub.18 aryl group or a C.sub.6-C.sub.18 aralkyl group, which may contain at least one heteroatom.

5. The onium-functionalized siloxane according to claim 1, wherein X is selected from Br, I or Cl.

6. The onium-functionalized siloxane according to claim 1, wherein A is a heteroatom selected from O or S.

7. A method for preparing the onium-functionalized siloxane having the general Formula (X) or (X-A) according to claim 1, wherein the method comprises: (i) providing a siloxane having the general Formula (I) or (I-A) ##STR00012## wherein R.sup.1 to R.sup.6, A, Z, X, n1, n2, and p are the same as defined for the Formula (X) or (X-A) above; and (ii) nucleophilic substitution of X on the siloxane of Formula (I) or (II-A) by a nucleophile containing at least one atom selected from the 15th or 16th group of the periodic table.

8. The method according to claim 7, wherein (a) the nucleophile used in (ii) is N, P, As, O, S or Se or (b) the nucleophilic substitution is done in the absence of a catalyst or (a) and (b).

9. The method according to claim 7, wherein the siloxane having the general Formula (I) or (I-A) is obtained by reacting a) at least one siloxane having the general Formula (II) or (II-A) comprising at least one hydrogen atom bonded to a silicon atom ##STR00013## wherein: R.sup.1 to R.sup.6 are the same as defined for the Formula (X) or (X-A) above; in Formula (II) n is an integer from 1 to 1000 and p is an integer from 0 to 1000; and in Formula (II-A) n is an integer from 1 to 100 and p is an integer from 0 to 100, wherein the sum p+n is equal to or higher than 3; b) at least one heterocyclic compound; and c) at least one compound having the general Formula (III) ##STR00014## wherein: X is selected from halogen atoms, pseudohalogens, Tf.sub.2N, BF.sub.4 or PF.sub.6; and R.sup.a is selected from the group consisting of a hydrogen atom or a linear, branched or cyclic hydrocarbon residue having 1 to 20 carbon atoms which may contain at least one heteroatom, wherein the reaction is catalyzed by at least one platinum catalyst.

10. The method according to claim 7, wherein the nucleophile is selected from the group consisting of amines, phosphines, arsanes, ethers, alcohols, thiols, sulfides, and selenium-containing molecules.

11. The method according to claim 7, wherein the nucleophile is selected from the group consisting of methylamine, ethylamine, dimethylamine, diethylamine, trimethylamine, trimethylamine, pyridine, piperidine, pyrrole, pyrroline, pyrrolidine, imidazole, 1-methyl-1H-imidazole, 1-butyl-1H-imidazole, pyrazole, pyrimidine, triazole, triazine, indole, quinoline, purine, adenine, guanine, hypoxanthine, xanthine, theobromine, caffeine, uric acid, isoguanine, and porphyrin.

12. The method according to claim 7, wherein the nucleophile is selected from trimethylamine, triethylamine, pyridine, 1-methyl-1H-imidazole, or 1-butyl-1H-imidazole.

13. The method according to claim 7, wherein the heterocyclic compound b) is selected from the group consisting of 1,2-propylene oxide, 1,2-butylene oxide, 2,3-butylene oxide, styrene oxide, cyclohexene oxide, tetrahydrofuran, tetrahydropyrane, oxepane, 1,4-dioxane, ε-caprolactones, and crown ethers.

14. An antimicrobial agent comprising the onium-functionalized siloxane according to claim 1.

15. An antimicrobial agent against molds, yeasts, fungi, gram-positive bacteria, or gram-negative bacteria comprising the onium-functionalized siloxane according to claim 1.

Description

EXAMPLES

Preparation of the Samples

Example 1: Preparation of 3-(4-bromobutoxy)methylsiloxane

[0111] ##STR00005##

[0112] A 250 ml three neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Then, 200 μL of Karstedt (2% of Pt in the catalyst, 0.1% mol in the mixture) and toluene (50 mL, dried over molecular sieves) were added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then tetrahydrofuran (18.5 mL, dried over molecular sieves) and allyl bromide (19.8 mL, 97%) were added into the system. Polyhydridomethylsiloxane (14.9 mL, Mn 1900 g/mol) were added dropwise. The mixture was stirred and refluxed at 100° C. inside under inert atmosphere (Ar) until complete conversion of the SiH groups was achieved (the reaction was followed by .sup.1H-NMR). The mixture (when necessary) was decolorized by adding activated carbon and an excess of pentane and stirred for 16 h at room temperature. The crude was filtrated trough celite, and the solvents and volatiles were evaporated under vacuum. The obtained product (yield 80-90%) was a colorless, transparent viscous liquid. The molecular weight and structure of the product was confirmed by GPC (Mn=4882 g/mol, PDI 2.190) and NMR spectroscopy.

Example 2: Preparation of (3-(4(polymethylsiloxane)butoxy) pyridinium bromide

[0113] ##STR00006##

[0114] A 25 ml two neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Ethanol (5 mL, dried over molecular sieves) and toluene (5 mL, dried over molecular sieves) are added. Halosilated intermediate obtained according to Example 1 is added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then pyridine (1.85 mL, 99%) was added into the system. The mixture was stirred (oil bath temperature: 75° C.) under inert atmosphere (Ar) until complete quaternization was achieved (the reaction was followed by .sup.1H-NMR). The solvents and volatiles were evaporated under vacuum. The obtained product (yield 95-100%) was a slightly yellow to yellow, transparent to milky, high viscous, sticky liquid. The molecular weight and structure of the product was confirmed by NMR spectroscopy.

Example 3: Preparation of (3-(4(polymethylsiloxane)pentoxy) pyridinium bromide

[0115] The procedure is the same as shown in Example 2. The halosilated intermediate has a 4-bromopentoxy-side-g roup.

Example 4: Preparation of (3-(4(polymethylsiloxane)hexyloxy) pyridnium bromide

[0116] The procedure is the same as shown in Example 2. The halosilated intermediate has a 4-bromohexyloxy-side-group.

Example 5: Preparation of (3-(4(polymethylsiloxane)butoxy) 1-methyl-1H-imidazol-3-ium bromide

[0117] ##STR00007##

[0118] A 25 ml two neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Ethanol (5 mL, dried over molecular sieves) and toluene (5 mL, dried over molecular sieves) are added. Halosilated intermediate obtained according to Example 1 is added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then 1-methyl-1H-imidazole (1.85 mL, 99%) was added into the system. The mixture was stirred (oil bath temperature: 75° C.) under inert atmosphere (Ar) until complete quaternization was achieved (the reaction was followed by .sup.1H-NMR). The solvents and volatiles were evaporated under vacuum. The obtained product (yield 95-100%) was a yellow to orange, transparent to milky, high viscous, sticky liquid. The molecular weight and structure of the product was confirmed by NMR spectroscopy.

Example 6: Preparation of (3-(4(polymethylsiloxane)pentoxy) 1-methyl-1H-imidazol-3-ium bromide

[0119] The procedure is the same as shown in Example 5. The halosilated intermediate has a 4-bromopentoxy-side-group.

Example 7: Preparation of (3-(4(polymethylsiloxane)hexyloxy) 1-methyl-1H-imidazol-3-ium bromide

[0120] The procedure is the same as shown in Example 5. The halosilated intermediate has a 4-bromohexyloxy-side-group.

Example 8: Preparation of (3-(4(polymethylsiloxane)butoxy) triethylammonium bromide

[0121] ##STR00008##

[0122] A 25 ml two neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Ethanol (5 mL, dried over molecular sieves) and toluene (5 mL, dried over molecular sieves) are added. Halosilated intermediate obtained according to Example 1 is added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then triethylamine (3.22 mL) was added into the system. The mixture was stirred (oil bath temperature: 75° C.) under inert atmosphere (Ar) until complete quaternization was achieved (the reaction was followed by .sup.1H-NMR). The solvents and volatiles were evaporated under vacuum. The obtained product (yield 95-100%) was a white, high viscous, waxy liquid. The molecular weight and structure of the product was confirmed by NMR spectroscopy.

Example 9: Preparation of (3-(4(polymethylsiloxane)butoxy) trimethylammonium bromide

[0123] ##STR00009##

[0124] A 25 ml two neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Tetrahydrofuran (5 mL, dried over molecular sieves) is added. Halosilated intermediate obtained according to Example 1 is added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then trimethylamine (5.32 mL, 28% in water, ca. 4.3 mol/L) was added into the system. The mixture was stirred (oil bath temperature: 75° C.) under inert atmosphere (Ar) until complete quaternization was achieved (the reaction was followed by .sup.1H-NMR). The solvents and volatiles were evaporated under vacuum. The obtained product (yield 95-100%) was a white, high viscous, waxy liquid. The molecular weight and structure of the product was confirmed by NMR spectroscopy.

Example 10: Preparation of (3-(4(polymethylsiloxane)butoxy) 1-butyl-1H-imidazol-3-ium bromide

[0125] ##STR00010##

[0126] A 25 ml two neck round bottomed flask was degassed under high vacuum (1.sup.−3 mbar) and flushed with argon. Ethanol (5 mL, dried over molecular sieves) and toluene (5 mL, dried over molecular sieves) are added. Halosilated intermediate obtained according to Example 1 is added into the flask under argon atmosphere and stirred at room temperature (20° C.) for a couple of minutes. Then 1-butyl-1H-imidazole (3.05 mL, 99%) was added into the system. The mixture was stirred (oil bath temperature: 75° C.) under inert atmosphere (Ar) until complete quaternization was achieved (the reaction was followed by .sup.1H-NMR). The solvents and volatiles were evaporated under vacuum. The obtained product (yield 95-100%) was a colourless, transparent to milky, viscous, sticky liquid. The molecular weight and structure of the product was confirmed by NMR spectroscopy.

Example 11: Preparation of (3-(4(polymethylsiloxane)pentoxy) 1-butyl-1H-imidazol-3-ium bromide

[0127] The procedure is the same as shown in Example 10. The halosilated intermediate has a 4-bromopentoxy-side-group.

Example 12: Preparation of (3-(4(polymethylsiloxane)hexyloxy) 1-butyl-1H-imidazol-3-ium bromide

[0128] The procedure is the same as shown in Example 10. The halosilated intermediate has a 4-bromohexyloxy-side-group.

[0129] NMR-Spectroscopy:

[0130] All NMR measurements were done on a Bruker 300 MHz, 400 MHz and 600 MHz instrument with deuterated DMSO and methanol as solvent. All the samples were measured at room temperature (297 K). The chemical shifts are given in ppm. The calibration of the chemical shifts in 1H spectra was carried out by using the shifts of the deuterated solvents (DMSO-d6, δH 2.49, 39.7; CD3δD, OH 3.31, 49.0).

[0131] GPC:

[0132] Gel permeation chromatography was carried out using HP1090 II Chromatography with DAD detector (HEWLETT PACKARD) at 40° C. Tetrahydrofuran (THF) was used as an eluent. THF was passed through three PSS SDV gel columns with molecular weight ranges of 102, 103 and 104 g-mol-1 with a flow rate of 0.9 ml.Math.min-1. The calibration of the device was carried out using polystyrene standards.

[0133] Antimicrobial Activity Tests

[0134] Kirby-Bauer Test (Zone of Inhibition):

[0135] The Kirby-Bauer Test is also known as Agar Diffusion Test and can be used for determination of antimicrobial activity in combination with diffusion properties. The utilized strains are Aspergillus brasiliensis (ATCC 16404), Staphylococcus aureus (ATCC 6538) and Exophiala dermatitidis (isolate). A suspension of the bacterial or fungal strain of interest is spread evenly over the face of a sterile agar plate. The antimicrobial test substrate (preferential liquid aggregation state) is applied to the center of the agar plate onto a small filter paper. The agar plate is incubated for a defined time at a temperature suitable for the test microorganisms. If the test substrate leaches from the filter paper into the agar and it further contains antimicrobial activity, a zone of inhibition is formed around the filter paper. The larger the number in Table 1, the better the antimicrobial effect.

[0136] Minimum Inhibitory Concentration (MIC):

[0137] The MIC is an antimicrobial testing method to detect the lowest concentration of an antimicrobial agent that prevents visible growth of bacteria or molds. The utilized strains are Candida albicans (ATCC 10231) and Staphylococcus aureus (ATCC 6538). The evaluation is done optically. The antimicrobial activity is given when the solution is still clear. The concentrations appear from a serial dilution.

TABLE-US-00001 TABLE 1 Test Results of Kirby-Bauer Test Zone of Inhibition [mm] (maximum 45 mm) Aspergillus Staphylococcus brasiliensis Exophiala aureus Samples (ATCC 16404) dermatitidis (ATCC 6538) DMSO 0.0 0.0 n.d Bardac © 4.5 11.4 12.1 Bardac © 1:10 2.0 5.3 8.0 Bardac © 1:100 1.5 4.3 4.5 Pyridine 0.0 1.0 1.0 Pyridine 1:10 0.0 0.0 0.0 Pyridine 1:100 0.0 0.0 0.0 1-methyl-1H-imidazole 3.5 12.3 6.5 1-methyl-1H-imidazole 0.0 0.0 0.0 1:10 1-methyl-1H-imidazole 0.0 0.0 0.0 1:100 1-Butyl-1H-imidazole 5.0 15.0 11.0 Example 2 1.0 4.4 2.0 Example 3 0.0 6.0 6.0 Example 4 0.0 7.0 6.0 Example 5 4.4 8.8 10.5 Example 6 0.0 6.0 7.0 Example 7 0.0 9.0 7.0 Example 10 3.5 7.8 9.9 Example 11 2.8 8.3 8.3 Example 12 1.8 8.3 8.0

[0138] DMSO was the utilized solvent in the test, the amines were utilized in the reaction, and Bardac© is a disinfectant. The numbers such as 1:10 or 1:100 show the dilution ratio.

[0139] MIC test results are given in ppm in Table 2.

TABLE-US-00002 TABLE 2 Test Results of MIC Staphylococcus aureus Candida albicans (ATCC 6538) (ATCC 10231) Example 2 25 625 Example 5 78 2500 Example 10 39 1250 Example 11 13 625 Example 12 13 625