CA1206973A - 3-(trimethoxysilyl) propyldidecylmethyl ammonium salts and method of inhibiting growth of microorganisms therewith - Google Patents

Abstract

TITLE
3-(TRIMETHOXYSILYL)PROPYLDIDECYLMETHYL AMMONIUM SALTS AND
METHOD OF INHIBITING GROWTH OF MICROORGANISMS THEREWITH

ABSTRACT

The growth of bacteria, fungi or the like is inhibited by contacting such microorganisms with an effective amount of certain silyl quaternary ammonium salts, e.g., 3-(trimethoxysilyl)propyldidecylmethyl ammon-ium chloride.

Description

~2(~69~3 Technical Fiela The present invention relates to certain silyl quaternary ammonium salts and a method of inhibiting the growth of bacteria and fungi therewith. In particular, the invention relates to the use of such salts as bacteri-cidal or fungicidal agents on texti'es or other sub-strates.

9~3 Backaround Art ., It is well known in the art that organosilicon quaternary ammonium compounds possess bacteriostatic, fun-gistatic and algaestatic and/or bactericidal, fungicidal and algaecidal properties. See, for example, U.S.
Patents Nos. 3,560,385; 3,730,701; 3,794,736; 3,817,739;
3,865,728; and 4,~05,025; and British Patent No.
1,386,876~ Thus, U.S. Patent No. 3,730,701 discloses a variety of silyl quaternary arnmonium compounds having a single long chain alkyl radical of from 11 to 22 carbon atoms. For example, one such compound, 3-(trimethoxy-silyl)propyl octadecyldimethyl ammonium chloride is a com-mercial antimicrobial product marketed by Dow Corning as "Bioguard Q 9-5700" (EPA No. 34292-1~. U.S~ Patent No.
15 3,794,736 describes a number of other organosilicon amines and salts thereo~ exhibiting antimicrobial activity against a ~ide variety of organisms.
In accordance with this invention there are pro-vided a number of silyl ~uaternary ammonium salts which have equal or greater antimicrobial activity than the pre-viously known compounds.

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~j Disclosure of Invention The present invention relates to certain silyl quaternary ammonium salts, particularly 3-(trimethoxy-silyl)propyldidecylmethyl ammonium salts, e.g., the flu-5 oride, chloride, bromide, iodide, sulfate,acetate and phosphatethereof, and their use as fungicides and bactericides on a variety of substances having reactive surfaces, particu-larly textile fabr~cs and fibers. As used herein, the term 'substances having reactive surfaces" or "surface reactive substratets) n is meant to include any material whose surface is able to form covalent chemical bollds with the didecylmethyl-substituted silyl quaternary ammonium compounds of the invention. It has now been found that these didecylmethyl substituted ammonium compounds more effectively inhibit the growth of such microorganisms, including, for example, both various gram-positive and gram-negative bacteria, than their known adjacent homo-logs.
While the specific site of action of the organo-silicon quaternary ammonium compounds is still underinvestigation it is known that the compounas are chemi-cally bonded to a variety of reactive surfaces and are not removed therefrom by repeated leaching or ~ashing with water. Thus, the compounds of the present invention are useful to impart durable bioactive properties to surfaces like natural and synthetic textile fibers, siliceous mate-rials like glass, stone and ceramics; metals; and also, leather, wood, plastic and the like. Generally, the sur-face reactive materials are treated by contacting the same with the bioactive compound, e.g., by either dipping, spraying, padding, or brushing the compound of the yresent ~ invention onto the substrates either prior to infestation by microorganisms to prevent the growth thereof, or after : infestation to kill and to prevent new growth thereof.

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12~6~73 The compounds of the present invention are active in solution as well as when applied to solid sur-faces. The antimicrobial compounds may thus be employed as the pure compounds, in aqueous solution or dispersion, or in organic solvent media.
Preferably, the compounds of the present inven-tion are dissolved in a suitable organic water miscible solvent forming a solution containing about 50% of the compound of the present invention as active ingredient.

..... . . .. . , .. .. .. . _ _ 12~6973 ~est Mode For Carrying Out The Invention In accordance with the present invention it has been found that 3-(trimethoxysilyl)propyldidecylmethyl ammonium salts exhibit antimicrobial properties which are superior to those of their known adjacent homologs. Such materials are thus useful for a variety of bactericidal, fungicidal and the like applications for which the use of silyl quaternary ammonium compounds has previously been proposed.
The compounds of the present invention may be prepared by known methods. Thus, the tertiary amine, i.e.,didecylmethyl amine, is reacted with an appropriate silane, e.g , 3-chloropropyltrimethoxysilane with or with-o~t the presence of a suitable solvent such as methanol.
The alkylation reaction of the tertiary amine proceeds smoothly resulting in the production of 3-(trimethoxy-silyl)propyldidecylmethyl ammonium chloride. Of course,other silanes may be similarly reacted to form other qua-ternary ammonium halides, e.g , the fluoride, bromide, or iodide, within the scope of the invention. ~imilarly, silanes incorporating sulfate or acetate anions may be converted to the corresponding quaternary ammonium salts, within the purview hereofO
Alternatively, the salts of the present inven-tion may be prepared by reacting didecylamines with thetrimethoxysilylpropylhalide, sulfate,acetate or phosphate in the presence of sodium methylate to yield the corresponding tertiary amines which are subsequently methylated to form the organosilicon quaternary ammonium salts. A further method for preparing the compound of the present invention includes the preparation of the allyldidecylamine, followed by hydrosilylation thereof with trimethoxysilane to produce 3-~didecylamino)propyltrimethoxysilane, which - is then treated with an appropriate methyl halide to yield the compound of-the present invention.

, _ . _, , . . _ . _ _ , . , _, . _ ... . . . .. . , _ .. _ _ _ . . . _ .. . .. , _ _ ~2C116~73 The preferred compound, 3-~trimethoxy -silyl)propyldidecylmethyl ammonium chloride, may directly contact the surface of the material to be treated by either spraying or brushing, or the surface reactive sub-5 strate may be immersed in the pure antimicrobial compoundor in a solution thereof in an appropriate solvent.
Surface reactive materials or substrates to which the compound of the invention can be chemically bonded include siliceous materials and metallic surfaces.
Leather, wood, rubber and plastic have also been shown to have reactive surfaces. Indeed, the preferred class of substrates having reactive surfaces to which the compound of the invention can readily bond comprises the natural and synthetic textile fibers and the corresponding fabrics thereof. Such natural fibers include cotton, wool, linen and felt; similarly bondable synthetic fibers include those comprised wholly of synthetic polymeric material such as viscose, cellulose acetate or triacetate; or nylons, polyether, vinyl polymers, including polyolefins, acrylics and modacrylics or the like; or blends of such materials with natural fibers.
Suitaole solvents in which the compound of the invention may be dissolved for bactericidal, fungicidal or similar applications include water and organic water mis-cible solvents like alcohols, such as methanol, ethanoland butanol; methyl Cellosolve~Yand ethyl Cellosolve;
ketones, such as methylethyl ketone. For textile treatment, solvents used in commercial dry cleaning processes, such as hydrocarbons, chlorinated hydrocarbons, ethers and benzene may alternatively be used.
As disclosed hereinabove, the active compound of the present invention may be applied to a variety of surfaces - by any suitable means. For example~ it is possible to spray the antimicrobial compound into shoes to inhibit or . , . . . _ .. , . . . . .. . . .. . _ .. . . ... . .. . . .. . . _ _ . . . . . . . . . .
. _ 12~6973 prevent growth of microorganisms therein. The pure com-pound or a solution thereof may also be applied to walls to prevent mold and mildew, or may be added to fillers used in paints to prepare paints with antimicrobial prop-erties. For treating textiles, the compound may be dis-persed in the solvents used in commercial dry cleaningprocesses and thus be readily brought into contact with textiles to be treated. Alternatively, the active com-pound may be applied to textile fabrics or fibers by exhaustion techniques, involving the use of closed systems in which the fibers or fabrics to be treated are immersed in a treating bath under preferably slightly elevated tem-perature conditions to effect absorption and fixation of the bioactive compound on the textile fibers and thus "exhaust" the same from the bath. Such techniques are more fully described, for example, in my prior U.S. Patent No. 3,788,803.
Another preferred method for applying the bioac-tive compound of the present invention to fabrics or textile fibers is by padding. The fabric to be treated may be immersed in a trough or padder containing a solu-tion of the antimicrobial compound. The concentration ofthe active ingredient in the solution is adjusted depending upon the ability of the substrate to pick up the antimicrobial compound from the bath. Of course, fin-ishing agents such as a softening agent or the like may be add~d to either the exhaustion or the padding bath.
Thus, in the preferred embodiments of the pre-sent invention for applying the antimicrobial compound of the invention to textile fibers or fabrics, the fibers or fabrics are immersed in a bath containing the compound (in pure or dissolved form) for a period of from about 3-5 - minutes to about 20-30 minutes at temperatures of from about 25 to 95 C., and preferably from about 40 to 70C. The amount of bioactive compound thus bonded to the . ~

c) . - ~l i2¢~6~73 textile fibers may vary, depending on the solvent and the particular structure of the textile employed. The active ingredient may be applied in an amount of from about 0.1%
to 1.0~ by weight of a textile substrate. Upon removal of the textile fibers from such an exhaustion or padding bath, the treated material may be dried in accordance with conventional practice in the art, thereafter woven, knitted, or otherwise converted to piece goods (if treated in fibrous form), and subjected to conventional finishing operations.
In the following examples all parts and percent-ages are by weight, and all temperatures in degrees Celsius~ unless otherwise indicated.
Example 1 - Preparation of 3-(Trimeth ~ ~ro~y~didecyl-methyl Ammonium Chloride In a 12-liter 3-neck round bottom reaction flask e~uipped with stirrer, thermometer and condenser was pla-- ced 4746 grams (15.2 moles) of didec~methylamine and 3160.7 grams (15.9 moles) 3-chloropropyltrimethoxysilane.
The solution was stirred with heating at llO~C. under a nitrogen atmosphere for 48 hours. The dark yellow/orange liquid was then placed under vacuum (5 torr), and approxi-mately 135 mls. residual 3-chloropropyltrimethoxysilane was removed. The remaining product was then added slowly to 7750 grams of methanol with stirring to produce a pro-duct containing 50% active materialL
Reaction with other, appropriately substituted propyltrimethoxysilanes gi~es other salts of the desired silyl quaternary ammonium compound, e.g., the bromides or iodides thereof.
Example 2 - Preparation of 3-(Trimethoxysilyl)Pro~yldidecylmethy~
_ _ _ _ _ Pmmonium Chloride In Methanol ~
- In a 2-liter single-neck preparation flask was placed 804 grams (2.58 moles) of didecylmethylamine, 536.5 grams (2.7 moles) of 3-chloropropyltrimethoxysilane and 4500 grams anhydrous methanol. The reaction mixture was stirred with heating to a gentle reflux under nitrogen for . _ _ . .. _ . . _ . ..... _ . _ .. . . _ _ . . _ .. _ _ . . _ . . .. . ... . ~ .. . .. . . _ ~ .. ~,, .. _ . . .

~, Z~6973 g _ 48 hours. The reaction was cooled to 35C. and 890 grams of anhydrous methanol was added. The resulting yel-low/orange solution contained 50 wt. % active material.
Example 3 - Com~arison of Antibacterial Activity_~
3-~Trimethoxysilyl)pro~yldiaecylmeth Ammonium Chloride With The Activity_Of Other Di-Long _ ain Alkyl Substituted _~ _ __ ~ano Silicon Quaternary Ammonium Compounds Against Gram Positive and Gram Negative Bacterla The activity of the compound of Example 1 was compared with various higher and lower adjacent homologs against a gram positive (Sta~ aureus ATCC 6538) and gram negative ~Klebsiella pneumoniae ATCC 4352) strain.
10 ml of a 10% aqueous solution of each bacteri-cide tested was prepared. Four serial dilutions were made by pipeting 1 ml of each 10% solution into a 10 ml vol-umetric flask and filling to the mark with water~ 0.1 ml of each serial dilution was added to 9.9 ml of sterile molten nutrient agar in tubes which were maintained at 47C. in a water bath. 0.1 ml of blank water was added to 9.9 ml of sterile molten nutrient agar to serve as a con-trol. 0.1 ml aliquots of a 24 hour culture of each test organism were pipeted into six sterile petri dishes pre-viously labeled 1000, 100, 10 , 1 and 0.1 and controlorganism. The contents of each tube was then poured into its respective petri dish, swirled and allowed to soli-- dify. The petri dishes were incubated, inverted, for 48 hours at 37C. The results were as follows:

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~) 12~6973 TAsLE I
Gram Positive Organism Gram Negative Organism Staph Aureus K. Pneumoniae _ Compounds 100 ppm 1000 ppm100 ppm. 1000 p~
Example 1 NGl NG NG NG
Control A G2 NG G NG
Control B G G G G
Control C5 G G G G
] NG = No growth

2 G = Growth

3 = 3-(trimethoxysilyl)propyldioctylmethyl ammonium chloride

4 = 3-(trimethoxysilyl)propyldidodecylmethyl ammonium chloride = 3-(trimethoxysilyl)propyldihexadecylmethyl ammonium chloride.

The compound of Example 1 prevented growth of the test bacteria at concentrations of 100 ppm of the test ~--compound, while the higher and lower homo]ogs thereof were unable to prevent bacteria growth at that concentration.
Example 4 Comparison of Antibacterial Activity of 3-(Trimethoxysilyl)propyl didecylmethyl Ammonium Chloride With The Activity of Mono- Long Chain Alkyl Substituted Organo-Silicon Quaternary Ammonium Compounds Aqainst Gram Positive and Gram Negative -~acteria.
The compound of Example 1 was also compared with related compounds having only one long chain alkyl radical. The test was conducted according to the procedure of Example 1. The followin~q results were obtained:

~ :`
`- ~LZ~ 73 TABLE II
Pseud.
CompoundsStaph aure~s K. pneumoniae E. coli aeruginosa (ATCC 6528) (ATCC 4352)(ATCC 11229) (QM 1468) (ppm) (ppm) (ppm) (ppm)

5 Example 1 100 100 ~ 4200 ~ 4200 Control ~6100 100 ~ 4200 ~ 4200 Control E 100 7 4200 ~ 4200 7 4200

6 3-(trimethoxysilyl)propyldecyldimethyl ammonium chloride 0 7 3-(trimethoxysilyl)propyloctadecyl~imethyl ammoni~m chloride commercially marketed as "Bioguar 9-5700" (~PA No. 3492-1) by Dow Corning.

15 The activity of the compound of Example 1 was as great as that of the mono- long chain substituted compound Control D. The compound of Example 1 exhibited antimicro-bial activity against the tested gram positive strain similar to that of the commercial product (Control E), but showed greater activity than the commercial product against the tested gram negative strain Klebsiella pneumoniae. ~hen the compounds of Example 1 and Control E were applied to polyester fabric, similar results were obtained against K. pneumoniae bacteria at concentrations of 0.25 to 0.5% active ingredient by weight of fabric while on 100% cotton faDric at concentration levels of 0.25 to 1.0% active ingredient by weight of fabric the compound of Example 1 again exhibited greater activity against K. pneumoniae than the commercial product (Control E).
From the preceding it may be seen that in accordance with the present invention new organosilicon - quaternary ammmoni~m salts are provided which have - -` improved bactericidal, fungicidal and similar-antimicrobial activities, and which may be applied to a c ~

variety of surface active materials. It should be understood that the preferred embodiments described above are for illustrative purposes only and are not to be con-strued as limiting the scope of the invention which is S properly delineated in the appended claims.

Claims (9)

Claims:

1. A silyl quaternary ammonium compound having the formula wherein X is selected from the group consisting of fluoride, chloride, bromide, iodide, sulfate, acetate and phosphate.

2. 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride.

3. A method of inhibiting the growth of Staph aureus and K. pneumoniae on surface reactive substrates by con-tacting said organisms with silyl quaternary ammonium compound of the formula wherein X is selected from the group consisting of fluoride, chloride, bromide, iodide, sulfate, acetate and phosphate in an amount effective to inhibit the growth of said organisms.

4. The method of claim 3, wherein the quaternary ammonium compound is 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride.

5. The method of claim 3 wherein said substrate is a siliceous material.

6. The method of claim 3 wherein said substrate is a metal.

7. The method of claim 3 wherein said substrate is selected from the group consisting of leather, wood, rubber and plastic.

8. The method of claim 3 wherein said substrate is made of natural or synthetic textile fibers.

9. The method of claim 8 wherein the quaternary compound is employed in an amount of from 0.1 to 1.0% by weight of said textile substrate.