WO2007120173A2 - N-halamine/quaternary ammonium polysiloxane copolymers - Google Patents

Abstract

Precursor N-halamine/quaternary ammonium random copolymers which are soluble in water for the purpose of functionalizing surfaces or materials so as to render them biocidal upon exposure to oxidative halogen solutions. The biocidal function can be imparted to the precursor N-halamine moiety either before or after siloxane bonding or adhesion to the surface or material. The biocidal surfaces and materials can then be used to inactivate pathogenic microorganisms such as bacteria, fungi, and yeasts, as well as virus particles, that can cause infectious diseases and those microorganisms that cause noxious odors and unpleasant coloring such as mildew. Examples of surfaces and materials which can be rendered biocidal include, but are not limited to, cellulose, chitin, chitosan, synthetic fibers, glass, ceramics, plastics, rubber, cement grout, latex caulk, porcelain, acrylic films, vinyl, polyurethanes, silicon tubing, marble, metals, metal oxides, and silica.

Description

N-HALAMINE/QUATERNARY AMMONIUM POLYSILOXANE COPOLYMERS

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 60/707,438, filed August 11, 2005.

STATEMENT OF GOVERNMENT LICENSE RIGHTS

Research leading to the present invention was supported, at least in part, under United States Air Force Grant No. FO8637-01-C-6004. The Government may have certain rights in the invention. BACKGROUND

A class of biocidal compounds having strongly biocidal functional groups known as N-halamines has recently been developed. N-halamines are heterocyclic amines that include groups such as hydantoins, oxazolidinones, and imidazolidinones having chlorine or bromine attached to a nitrogen of the heterocyclic ring. A precursor N-halamine refers to the non-halogenated heterocyclic amine. N-halamines have the ability to be regenerated when the halogen is depleted. N-halamines have been linked to various polymers, including polysiloxanes. A different class of biocidal compounds, known as quaternary amines, only have a weakly biocidal quaternary ammonium cation and are nonregenerable. Thus, they are much less desirable in comparison to N-halamines. Polysiloxane polymers and monomers described in U.S. Patent No. 6,969,769 having N-halamine groups have an advantage over previous technology, such as quaternary amines, in biocidal efficacy in terms of both the required contact times and increased spectrum of activity against pathogens. However, these N-halamine polysiloxane polymers are not soluble in pure aqueous media. Therefore, N-halamine polysiloxane polymers are limited in the preparation of substrates involving a non-aqueous solvent.

SUMMARY

As used herein, "copolymer" when used either alone or in connection with "polysiloxane" refers to a polysiloxane polymer which has both pendant hydantoin groups and pendant quaternary ammonium groups regardless of how made. The pendant hydantoin groups and the pendant quaternary ammonium groups are randomly attached to the polysiloxane copolymer backbone. The polysiloxane copolymers having pendant hydantoin groups and pendant quaternary ammonium groups described herein represent a significant improvement over the polysiloxane polymers described in U.S. Patent No. 6,969,769 in that the polysiloxane copolymers of the present invention can be rendered soluble in water for use in coating applications using a purely aqueous solvent. Embodiments of the polysiloxane copolymers include both the precursor N-halamine and N-halamine hydantoinyl group. The polysiloxane copolymers are rendered soluble by attaching a specific fraction of quaternary ammonium groups to the polysiloxane.

In one embodiment in accordance with the present invention, a polysiloxane copolymer is represented by the formula:

The quaternary ammonium group is represented by the formula:

The hydantoin group is represented by the formula:

wherein R₁ is a Cl to C20 alkyl group; R₂ is a Cl to C6 alkyl group; R₃ is a Cl to C6 alkyl group; R₄ is a Cl to C4 alkyl group or phenyl group; R₅ is a Cl to C4 alkyl group or phenyl group; or

R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

L₁ is a Cl to C8 linker alkylene group; L₂ is a Cl to C 8 linker alkylene group; X is H, Cl, or Br;

Air is a counteranion, such as Cl", Br", or OH"; n is a number representing a mole percent from 10% to 90%; and m is a number representing a mole percent from 10% to 90%.

The polysiloxane copolymer is substantially soluble in water, when m is a number representing at least 25% mole percent. The polysiloxane copolymer may be a random polysiloxane copolymer wherein the hydantoin groups and quaternary ammonium groups are randomly attached to the polysiloxane copolymer.

Other embodiments of the present invention relate to the synthesis of polysiloxanes copolymers, and to the use of polysiloxane copolymers that are soluble in water for the purpose of constructing coatings and materials that can be rendered biocidal by exposure to halogen solutions either before or after curing the surface or material to a substrate. The biocidal coatings can inactivate pathogenic microorganisms such as bacteria, fungi, and yeasts, as well as virus particles that can cause infectious diseases and those microorganisms that cause noxious odors and unpleasant coloring such as mildew. The coatings are compatible with a wide variety of substrates including cellulose, chitin, chitosan, synthetic fibers, glass, ceramics, plastics, rubber, cement grout, latex caulk, porcelain, acrylic films, vinyl, polyurethanes, silicon tubing, marble, metals, metal oxides, and silica.

Another embodiment of the present invention relates to a method of rendering a surface or material biocidal by attaching the polysiloxane copolymers, when X in the structure above is chlorine or bromine, through reaction or interaction with the hydroxyl moieties. Another embodiment of the present invention relates to a method of rendering a surface or material biocidal by attaching the polysiloxane copolymers when X in the structure above is hydrogen, through reaction or interaction with the hydroxyl moieties, and then exposing the modified surface to a source of oxidative chlorine or bromine. DESCRIPTION OF THE DRAWINGS

The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same become better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein: FIGURE 1 is a graph of the Fourier Transform Infrared Spectroscopy (FTIR) spectra of the homopolymers poly[3-(5,5-dimethylhydantoinylpropyl)siloxane] and poly[3-dimethyldodecylammoniumsiloxane chloride] and of the copolymer poly[3-(5₅5-dimethylhydantoinylpropyl)siloxane-co-3-dimethyldodecylammoniumpropyl siloxane chloride]; FIGURE 2 is a scheme illustrating a method of making polysiloxane copolymers in accordance with one embodiment of the present invention; and

FIGURE 3 is a scheme illustrating a method of making polysiloxane copolymers in accordance with one embodiment of the present invention.

DETAILED DESCRIPTION As used herein, "unhalogenated polysiloxane copolymer" refers to the compound having the structure:

wherein, R₁ is a C 1 to C20 alkyl group; R₂ is a Cl to C6 alkyl group;

R₃ is a Cl to C6 alkyl group;

R₄ is a Cl to C4 alkyl group or phenyl group;

R₅ is a Cl to C4 alkyl group or phenyl group; or

R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

L₁ is a Cl to C8 linker alkylene group;

L₂ is a Cl to C8 linker alkylene group;

X is hydrogen;

An^" is a counteranion, such as Cl", Br, or OH"; n is a number representing a mole percent from 10% to 90%; and m is a number representing a mole percent from 10% to 90%.

The copolymer is weakly biocidal when the substituent X comprises a hydrogen atom. Mole percentages for the numbers n and m are based on the combined moles of hydantoin and quaternary ammonium moieties. The polysiloxane copolymer may be a random polysiloxane copolymer wherein the hydantoin groups and quaternary ammonium groups are randomly attached to the silicon atoms on the polysiloxane copolymer.

As used herein, "the halogenated polysiloxane copolymer" refers to the compound having the structure:

wherein,

R₁ is a Cl to C20 alkyl group;

R₂ is a Cl to C6 alkyl group;

R₃ is a Cl to C6 alkyl group;

R₄Is a Cl to C4 alkyl group or phenyl group; R₅ is a Cl to C4 alkyl group or phenyl group; or

R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

L₁ is a Cl to C8 linker alkylene group; L₂ is a Cl to C8 linker alkylene group;

X is Cl or Br; and

An^" is a counteranion, such as Cl", Br, or OH"; n is a number representing a mole percent from 10% to 90%; and m is a number representing a mole percent from 10% to 90%. The copolymer is strongly biocidal when the substituent X comprises a chlorine or bromine atom. The polysiloxane copolymer may be a random polysiloxane copolymer wherein the hydantoin groups and quaternary ammonium groups are randomly attached to the silicon atoms on the polysiloxane copolymer. ^l

As used herein, "modified substrate" refers to a substrate surface or substrate material to which a species having either of the structures described above has been attached through a reaction or interaction with the hydroxyl moieties, either through a covalent bond, such as an ether linkage, or through an adhesive interaction, such as hydrogen bonding or a physical attraction. If X in the hydantoinyl functional group is chlorine or bromine, the surface or material will be strongly biocidal. If X in the hydantoinyl functional group is hydrogen, the surface or material will be weakly biocidal, but the surface or material can be rendered strongly biocidal by exposing it to a source of oxidative chlorine or bromine.

Polysiloxane copolymers having pendant hydantoin groups and quaternary ammonium groups can be synthesized by reacting a poly(haloalkyltrialkoxysilane) polymer, such as poly(chloropropyltriethoxysilane) or poly(chloropropyltrimethoxysilane), with some fraction of an alkali metal salt of a 5,5-dialkylhydantoin, such as the potassium or sodium salt of 5,5-dimethylhydantoin, and some fraction of a tertiary amine, such as dodecyldimethylamine, in a solvent, such as dimethylformamide (DMF). The reactions of the poly(haloalkyltrialkoxysilane) polymer with the alkali metal salt of a 5,5-dialkylhydantoin and the tertiary amine can be conducted via two paths. The first is in two reaction steps using each nucleophile in sequence as illustrated in FIGURE 2. In this path, the poly(haloalkyltrialkoxysilane) polymer has haloalkyl groups that are reactive at the imide nitrogen of the 5,5-dialkylhydantoin as illustrated in FIGURE 1. Therefore, the hydantoin groups become attached to the poly(haloalkyltrialkoxysilane) polymer via the imide nitrogen. The amount of the alkali metal salt of the 5,5-dialkylhydantoin is controlled so that not all the haloalkyl groups of the poly(haloalkyltrialkoxysilane) become attached to hydantoin groups leaving unreacted haloalkyl groups. In the second step, a tertiary amine is reacted with the remaining unreacted haloalkyl groups of the poly(haloalkyltrialkoxysilane) polymer that did not attach to hydantoin groups, thereby yielding the polysiloxane copolymer having both hydantoin groups and quaternary ammonium groups in a desired ratio. Such sequential reactions to attach the hydantoins and tertiary amines to the poly(haloalkyltrialkoxysilane) can be carried out in the presence of a solvent, such as DMF, at temperatures of about lOCPC, and for about 5 or 8 hours, depending on the amount and type of reactant and the temperature.

A second path to the polysiloxane copolymer is illustrated in FIGURE 3. In this path, the two nucleophilic compounds, hydantoins and tertiary amines, are reacted simultaneously with the poly(haloalkyltrialkoxysilane) polymer. During this reaction, the haloalkyl groups can attach to either the hydantoin groups or the tertiary amine groups. The respective amounts of the alkali metal salt of the 5,5-dialkylhydantoin and tertiary amine are controlled to provide the desired ratio in the polysiloxane copolymer product. Such simultaneous reaction to attach the hydantoins and tertiary amines to the poly(haloalkyltrialkoxysilane) can be carried out in the presence of a solvent, such as DMF, at temperatures of about IOCPC for about 12 hours, depending on the amount of reactants and the temperature.

The polysiloxane polymer will be soluble in purely aqueous media when the mole percent of quaternary ammonium groups is at least 25%, based on the combined moieties of hydantoinyl groups and quaternary ammonium groups. In general, the haloalkyltrialkoxysilane or a poly(haloalkyltrialkoxysilane) polymer, the alkali metal salt of a 5,5-dialkylhydantoin, the tertiary amine, and the solvent used in the synthesis of the polysiloxane copolymers are inexpensive and commercially available from vendors, such as Aldrich Chemical Company (Milwaukee, WI). Unhalogenated polysiloxane copolymers include the precursor N-halamine hydantoinyl groups. Unhalogenated polysiloxane copolymers can be rendered biocidal by reacting the unhalogenated polysiloxane copolymers dissolved in water at ambient temperature with free chlorine from sources such as gaseous chlorine, sodium hypochlorite bleach, calcium hypochlorite, chloroisocyanurates, and dichlorohydantoins. In the case of dichlorohydantoins, the chlorine moiety on the imide nitrogen should transfer to the more stable amide nitrogen of the hydantoinyl groups attached to the polysiloxane copolymer. Likewise, biocidal brominated polysiloxane copolymers can be prepared by exposing the unhalogenated polysiloxane copolymers dissolved in an aqueous solution at ambient temperature to free bromine from sources such as molecular bromine liquid, sodium bromide in the presence of an oxidizer such as potassium peroxy monosulfate, and brominated hydantoins. Halogenation can also be effected in organic solvents employing free radical halogenating agents such as t-butyl hypochlorite. The unhalogenated and halogenated polysiloxane copolymers have hydroxy groups attached to silicon atoms that allow the polysiloxane copolymers to be bound to a substrate surface or substrate material either through covalent bonding through an ether linkage or through an adhesive interaction, such as hydrogen bonding or a physical attraction, depending on the nature of the surface or material. Modifying a substrate by attaching polysiloxane copolymers can be accomplished by exposing the substrate surface or substrate material to a solution of the unhalogenated polysiloxane copolymers at temperatures in the range of 0 to 30CPC, more preferably, 20 to 15O³C₅ depending upon the nature of the surface or material. Alternatively, the modification of substrates by attachment of polysiloxane copolymers can also be accomplished by exposing the substrate surface or substrate material to a solution of the halogenated polysiloxane copolymers at temperatures in the range of 0 to 60³C, more preferably 20 to 4CPC, depending upon the nature of the surface or material. The solvent for the halogenated or unhalogenated polysiloxane copolymers can be aqueous or organic materials, such as ethanol. However, alcohols are less useful for dissolving the halogenated polysiloxane copolymers because alcohols partially protonate the nitrogen of the heterocyclic ring liberating halogen. Base can also be added to the aqueous solutions to enhance the solubility of the polysiloxane copolymers. Other additives can be introduced to the solutions of the polysiloxane copolymers to enhance binding to the substrate surface or materials, e.g., potassium thiocyanate for binding to cellulose. The solutions containing the polysiloxane copolymers can be exposed to the substrate surfaces or materials by soaking, spraying, spreading, and the like. Following drying of the solution on the substrate surface or material, the dried polysiloxane copolymer coating should be cured for 15 to 30 minutes at a slight or moderate elevated temperature (the value of which will depend upon the surface or material composition, e.g., 25³C for paper, 95³C for cotton fibers and glass, etc.).

The substrate surface or material can be rendered biocidal if the unhalogenated polysiloxane copolymers were employed in the coating process by exposure to a source of oxidative halogen, such as an aqueous solution of sodium hypochlorite bleach, calcium hypochlorite, chloroisocyanurates, and dichlorohydantoins, or an organic solution of t-butyl hypochlorite, for chlorination, or an aqueous solution of molecular bromine liquid, sodium bromide in the presence of an oxidizer such as potassium peroxy monosulfate, and brominated hydantoins, for bromination. For example, an aqueous solution of 5 to 10% Clorox® can be used for efficient chlorination, which can be accomplished at ambient temperature by spraying or soaking the substrate surface or material. After halogenation, the substrate surface or material should be allowed to dry in air at temperatures up to 4O³C (ambient temperature is preferable if time permits) and rinsed with water. The substrate surface or material will then exhibit strong biocidal properties for various time periods dependent upon the composition of the substrate surface or material, the use pattern (contact with organisms and halogen demand), and the storage temperature, etc. When the bound halogen content becomes too low for efficient biocidal activity, the substrate surface or material can be recharged with halogen in the same manner as for the initial halogenation noted above. Even when all oxidative halogen is depleted, the surface will remain weakly biocidal due to the presence of the quaternary ammonium functional groups.

An alternate method of attaching biocidal moieties to substrates utilizing ,siloxane chemistry would be first to bond a haloalkyltrialkoxysilane containing a substituted electrophilic alkyl functional group to the substrate surface, either through covalent or adhesive interaction, and then second to bond the N-halamine or precursor N-halamine hydantoin and the tertiary amine to the already tethered haloalkyltrialkoxysilane through nucleophilic substitution reactions. For example, monomers of chloropropyltriethoxysilane could be used to simultaneously synthesize a polysiloxane polymer while binding the polymer to the surface in preparation for attaching hydantoinyl - and quaternary ammonium groups thereto. The chloropropyl functionality thus tethered through the polysiloxane could be reacted with the alkali metal salt of a 5,5-dialkylhydantoin, such as 5,5-dimethylhydantoin, and a tertiary amine, such as dodecyldimethylamine, sequentially or simultaneously, and in the appropriate proportions to produce anchored precursor N-halamine hydantoinyl and quaternary ammonium groups to the surface. The precursor N-halamine hydantoinyl groups could then be halogenated in situ, as described above, to render the surface biocidal. Such reactions to attach the hydantoins and tertiary amines to a substrate tethered polysiloxane can be carried out in the presence of a solvent, such as DMF, at a temperature of about IOCPC for about 5 to 12 hours, depending on the amount and type of reactant, and whether the hydantoins and tertiary amines are being reacted sequentially or simultaneously. The above described process thus avoids having to prepare the polysiloxane copolymer prior to attaching the copolymer to the surface. Yet another means of attaching biocidal moieties to surfaces utilizing siloxane chemistry includes making polysiloxane copolymers by reacting monomers of a (3-alkyl-5,5-dialkylhydantoinyl)trialkoxysilane, such as

(3-propyl-5,5-dimethylhydantoinyl)triethoxysilane, with monomers of a [3-(trialkylammonium)alkyl]trialkoxysilane, such as [3-(dodecyldimethylammonium chloride)propyl]triethoxysilane, in a solvent and an acid and at the conditions of time and temperature described generally above, so as to produce a polysiloxane copolymer product. The respective amounts of monomers in the reaction are controlled to give a mole percent from 10% to 90% of hydantoinyl moieties and a mole percent from 10% to 90% of quaternary ammonium moieties in the polysiloxane copolymer. Polysiloxane copolymers can then be anchored to a surface and then be halogenated in situ, as described above, to render the surface biocidal. Generalized formulae for monomers of (3-alkyl-5,5-dialkylhydantomyl)trialkoxysilane and

[3-(trialkylammonium)alkyl]trialkoxysilane are give below.

(a) (3 -alkyl-5 , 5 -dialkylhydantoinyl)trialkoxy silane.

R

I O

R-O- Si-O-R

(b) [3 -(trialkylammonium)alkyl]trialkoxysilane R

O

Vj Ol vj r\

wherein,

R is a Cl to C6 alkyl group Ri is a C 1 to C20 alkyl group;

R₂ is a Cl to C6 alkyl group; R₃ is a Cl to C6 alkyl group; R₄ is a Cl to C4 alkyl group or phenyl group; R₅ is a Cl to C4 alkyl group or phenyl group; or R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

Li is a Cl to C8 linker alkylene group; L₂ is a Cl to C8 linker alkylene group; X is H, Cl, or Br; and An^" is a counteranion, such as Cl", Br, or OH".

The mechanism of action of the biocidal surfaces and materials produced from the halogenated polysiloxane copolymers described herein are believed to be a result of surface contact of the organism with chlorine or bromine moieties covalently bound to the hydantoinyl functional groups on the bound polysiloxane copolymer, as well as with the quaternary ammonium functional groups. The chlorine or bromine atoms are transferred to the cells of the microorganisms where they cause inactivation through a mechanism not completely understood, but probably involving oxidation of essential groups contained within the enzymes comprising the organisms. The quaternary amine functional groups are weakly biocidal presumably due to cell-membrane disruption caused by the positively charged quaternary nitrogen. A marked advantage of the biocidal surfaces and materials produced with the polysiloxane copolymers over prior technology is that they are much more effective biocidally against pathogenic microorganisms encountered in medical applications, such as Staphylococcus aureus and Pseudomonas aeruginosa, than are commercial biocides, such as the pure quaternary ammonium salts, so they can serve a dual function, i.e., inactivation of disease-causing pathogens and of odor-causing microorganisms. For this reason, the polysiloxane copolymers will have widespread use in medical settings, such as hospitals, nursing facilities, and research laboratories. The polysiloxane copolymers are also useful for biocidal applications in a variety of other industrial settings as well as in the home. A few examples of surfaces and materials that can be made biocidal with polysiloxane copolymers include envelopes, surgical gowns and gloves, sheets, bandages, sponges, table and counter tops, glassware, plastic items, synthetic fibers, wood, chitin, chitosan, cement grout, latex caulk, porcelain, acrylic films, vinyl, polyurethanes, silicon tubing, marble, and metals. In general, any surface or material having an affinity to bond to a hydroxyl group through covalent bonding, hydrogen bonding or a physical attraction, is a suitable candidate for rendering biocidal.

The present invention is more particularly described in the following examples that are intended as illustrative only, since numerous modifications and variations therein will be apparent to those skilled in the art. EXAMPLE 1

1. PREPARATION OF REPRESENTATIVE HYDANTOINYL/QUAT

SILOXANE POLYMERS AND COPOLYMERS

The starting material for all of the homopolymers and copolymers discussed in this Example was the polymer poly(3-chloropropylsiloxane)(PCPS) prepared from the monomer 3-chloropropyltriethoxysilane (Aldrich Chemical Company, Milwaukee, WI). (See Worley, S.D., et al., Surf. Coat. Intern. Part B: Coat. Trans. 88, 93-99, 2005). The homopolymer poly[3-(5,5-dimetliylhydantoinylpropyl)siloxane](PHS) was synthesized by reacting PCPS with the potassium salt of 5,5-dimethylhydantoin (Aldrich Chemical Company, Milwaukee, WI); characterization data (IH NMR (Bruker 400 MHz), IR (Shimadzu IR Prestige-21 FTIR); and EA (Atlantic Microlabs)) have been reported. (See Worley, S.D., et al, Surf. Coat. Intern. Part B: Coat. Trans. 88, 93-99, 2005). Yields, based upon a repeating unit, exceeded 95%. The quaternary ammonium homopolymer poly[3-dimethyldodecylammoniumsiloxane chloride](PQS) was prepared by reacting PCPS with dimetliyldodecylamine (Aldrich Chemical Company, Milwaukee, WI) in a 1:1 molar ratio based upon a repeating unit of PCPS. For example, in one experiment 6.92 g (0.05 mol) of PCPS were dissolved in 50 mL of dimethylformamide (DMF). To this solution were added 11.2 g (0.05 mol) of 95% dimethyldodecylamine. The reaction mixture was stirred at IOCPC for 12 hours. After cooling to ambient temperature, the KCl produced in the reaction and the DMF solvent were removed by filtration and evaporation, respectively. Any DMF residual was removed with a hexane extraction, and the white solid product was dried under vacuum overnight at 5CPC before further use. The yield, as determined by a titration procedure to be described, was about 85% based upon a repeating unit. Some spectroscopic data for the PQS were: ¹H NMR (d₆ DMSO) δ θ.86, 1.25, 1.66, 1.79, 3.07, 3.33, 3.63; IR (KBr) 702, 914, 1129, 1468, 1484, 1628, 2854, 2925, 2956, 3000-3700 cm^"1.

The polysiloxane copolymers, poly[3-(5,5-dimethylhydantoinylpropyl)siloxane- co-3-dimethyldodecylammoniumpropylsiloxane chloride] (PHQS), were prepared by two different procedures. In a two-step process illustrated in FIGURE 2, the molar ratio of hydantoin salt and PCPS were controlled in the reaction of the first step, and then the molar ratio of dimethyldodecylamine and the product of the first step were controlled in the reaction of the second step to produce PHQS with a desired mole percent for hydantoin moieties and a mole percent for quaternary ammonium moieties. For example, to produce a PHQS with values of n and m of 0.5, 6.92 g (0.05 mol) of PCPS was mixed with 4.15 g (0.025 mol) of the potassium salt of 5,5-dimethylhydantoin in 5O mL of DMF. After stirring the mixture for 5 hours at 100³C, and removing the KCl produced by filtration, 5.62 g (0.025 mol) of 95% dimethyldodecylamine were added, and the reaction mixture was stirred at IOCPC for an additional 8 hours. Removal of DMF and drying overnight under vacuum at 5CPC produced a 78.3% yield of a white solid product (¹H NMR (d₆ DMSO) δθ.56, 0.85, 1.26, 1.56, 1.66, 2.68, 3.04, 3.33, 3.60; IR (KBr) 699, 774, 912, 1122, 1279, 1421, 1450, 1469, 1707, 1768, 2855, 2927, 3000-3700 cm^"1.

In a one-step process illustrated in FIGURE 3, PCPS, the potassium salt of 5,5-dimethylyhydantoin, and dimethyldodecylamine were simply mixed in a molar ratio of 0.5:0.25:0.25, respectively, in one pot. The reaction was run with stirring at IOCPC for 12 hours and worked up as discussed above; the yield of white solid was 77.5% in this case. The two methods gave very similar products as determined by ¹H NMR and IR. Characterization of the various polymers and copolymers synthesized in this example is problematic. For the PHS, the 95% yield based upon a repeating unit and the ¹H NMR, IR, and EA data all indicated that almost all of the propyl groups on PCPS were substituted with hydantoinyl functional groups. However, the molecular weight of PHS does vary depending upon the preparation procedure (e.g., about 11,00O D using the method cited herein, but about 4000 D if a hydantoinylpropylsilane is polymerized in acidic solution); nevertheless, the biocidal properties of PHS do not seem to vary with molecular weight. In the case of PQS, the modified titration procedure described in Section 4 below suggested that the yield was only about 85%. Probably, the reason for less conversion for PQS than for PHS can be attributed to steric hindrance caused by the large dodecyl group.

For the copolymers, PHQS characterization becomes more difficult. It can be assumed that the copolymers are random ones with varying substitution patterns on the backbone with hydantoin and quaternary ammonium functional groups. That both types of functionalities are present can be seen from the IR spectra in FIGURE 1 for a copolymer PHQS which was designed to be about 1:1 in the two types of functionalities. The two carbonyl stretching vibrational modes for any hydantoin compound give rise to two IR bands in the 1700-1810 cm^'1 range, which are clearly present for PHS and the 1:1 PHQS polymers. Furthermore, the presence of the C-H stretching modes with corresponding IR bands at 2854-2855 and 2925-2927 cm^'1 for PQS and PHQS indicate the presence of quaternary ammonium functional groups in the PHQS copolymer. The data in Table 1 illustrate further the relative difficulty of functionalization of the siloxane polymers with quaternary amines versus hydantoins. Clearly as the value ofm in Figure 1 increases relative to n, the reactivity of the siloxane with the dimethyldodecylamine declines.

TABLE 1

Comparison of the weight percent of quaternary ammonium functional group in the siloxane polymers as predicted theoretically with those determined by ion association titration.

2. COATING PROCEDURE

The various homopolymers and copolymers were coated onto the surfaces of cotton swatches (Style 400 Bleached 100% Cotton Print Cloth, Testfabrics, Inc., West Pittston, PA) by soaking the swatches in baths containing about 0.15 mol/L of each compound dissolved in distilled water for 15 minutes. Since PHS has very low solubility in water, a 1 : 1 w/w mixture of ethanol and water was used for this homopolymer; this procedure was also necessarily followed for the copolymer in FIGURE 2 in which the values of n and m were 3 and 1 , respectively. After the soaking procedure, the coated swatches were cured at 95°C for 1 hour and then further at 145°C for 20 minutes. Then the swatches were washed in 0.5% detergent solution for 15 minutes followed by several water rinses to remove any weakly bonded coating.

The primary goal of this work was to enhance solubility of PHS in water, so as to avoid as much as possible organic solvents. Although exact solubilities were not measured, it was found that greater than the 5% solubility necessary in an aqueous coating bath was obtained for PQS and PHQS for n values (FIGURE 2) less than or equal to 0.5, i.e., a hydantoin: quaternary ammonium ratio of 1:1. For a hydantoin: quaternary ammonium ratio of about 3:1, the solubility decreased to about 3%. The PHS homopolymer could only be dissolved in ethanol/water mixtures. The cotton swatches coated in this work, and subsequently chlorinated, retained their white color and did not undergo significant deterioration.

3. CHLORINATION PROCEDURE

The coated cotton swatches were chlorinated by soaking them in a 10% aqueous solution of NaOCl household bleach (Clorox, Inc., Oakland, CA) buffered to pH 7 at ambient temperature for 45 minutes. The chlorinated swatches were washed with water and dried at 45⁰C for 1 hour to remove any occluded free chlorine. The loading of bound chlorine on the swatches was determined as described below. 4. ANALYTICAL TITRATION PROCEDURES

Two types of titration procedures were used, one to estimate oxidative chlorine loadings in PHS and in the copolymers PHQS, the other to estimate quaternary ammonium content in PQS and in the PHQS copolymers. For determination of oxidative chlorine (Cl⁺) content, a modified iodometric/thiosulfate titration procedure was employed in which the usual solvent water was necessarily replaced by a mixture of ethanol and 0.1 N acetic acid (9:1 v/v). For example, about 0.3 g of coated and chlorinated cotton swatch material was suspended in a solution of 90 mL ethanol and 1O mL 0.1 N acetic acid. After addition of 0.2 g KI, the mixture was titrated with 0.0375 N sodium thiosulfate until the yellow color disappeared at the end point. The weight percent Cl⁺ on the cotton swatch could then be determined from the equation below:

% O⁺ = [N X V X 35.45 I (2 X W)] X 100% . (1)

where N and V are the normality (eqv/L) and volume (L), respectively, of the Na₂S₂O₃ consumed in the titration, and W is the weight in g of the cotton swatch sample.

The quaternary ammonium contents of PQS and the PHQS copolymers could not be determined for the coated cotton swatches. However, a modified ion association titration method developed for quaternary ammonium salts was used to estimate the percentage of quaternary ammonium functional groups present in the polymers. (See Sakai, T. Anal. Sci. 17, 1379-1382, 2001) In this method, 0.020 to 0.050 g of PQS or

PHQS was dissolved in 50 mL of 0.05 N acetic acid. To the solutions were added

3 drops of 0.5% bromophenol blue/ethanol as an indicator. The titrant was

0.0100 N sodium tetraphenylborate, and the end point was determined by a color change from blue to light yellow. The weight percent quaternary ammonium was calculated according to the following equation:

% Quat = [N X V X M I W] X l 00% (2)

where N and V are the normality (eqv/L) and volume (L) consumed, respectively, of sodium tetraphenylborate solution, M is the molecular weight of a quaternary ammonium repeating unit, and W is the weight in g of the PQS or PHQS sample. For the cotton swatches coated with all of the polymers, it was found that the traditional iodometric/thiosulfate titration procedure employing dilute acetic acid, KI, and starch was best modified by use of a solution containing a 9:1 (v/v) ratio of ethanol and 0.1 N acetic acid without the usual starch indicator. The problems were accentuated as the quaternary ammonium content of the coatings increased. As can be seen in Table 2, the modification greatly accelerated the titration procedure by producing an easily observed end point (yellow to clear). The presence of starch in the titration causes a deep blue color on the swatches themselves which does not disappear during the titration leading to difficulty in determining end points. In addition, for those samples containing PQS and PHQS copolymers, the I₃ ^" formed during the iodometric titration procedure can associate strongly with the positively charged nitrogen of the quaternary ammonium functionality in the coating leading to large errors in the oxidative Cl determination in a normal titration procedure. The presence of ethanol circumvents this problem as I₃ ^" is very soluble in this solvent leading to rapid and accurate titration with the sodium thiosulfate. From the data in Table 2, one can see that PHQS swatches containing a hydantoin.-quaternary ammonium ratio of about 1 :3 did not indicate the presence of any oxidative chlorine using the traditional iodometric/thiosulfate titration procedure. The use of the modified titration procedure discussed herein for oxidative chlorine determinations for N-halamine polymeric coatings is recommended. Although the typical chlorine loadings reported in Table 2 may seem low, it will be demonstrated in section 5 that the biocidal efficacies of the coated swatches are quite good.

TABLE 2

Comparison of oxidative chlorine titration methods for coated cotton swatches containing chlorinated siloxane polymers and copolymers.

^a Sample suspended in 0.1 N acetic acid solution for iodometric/thiosulfate titration (see text). ^b Sample suspended in ethanol/0.1 N acetic acid (9:1 v/v) solution for iodometric/thiosulfate titration (see text).

5. BIOCIDAL EFFICACY TESTING

One inch square cotton swatches, some uncoated to serve as controls, others coated with PHS, but unchlorinated, to serve as a second type of control, and others coated with chlorinated PHS, chlorinated PHQS, or PQS, were rinsed thoroughly with water. All samples containing quaternary ammonium functional groups were vortexed for 30 seconds in 10 mL of distilled, deionized water to remove any occluded quaternary ammonium salt. These swatches were removed from the vortex tube, and the water was tested for the presence of eluted quaternary ammonium by adding 2 drops of 0.5% bromophenol blue indicator and 1 drop of 4 N acetic acid. A blue color indicated the presence of some eluted quaternary ammonium in the water. Such samples were subjected to further rinsing in distilled, deionized water until the eluted water from the vortex tube, after exposure to bromophenyl blue, remained yellow.

Dried swatches were then challenged with either Staphylococcus aureus

ATCC 6538 or Escherichia coli O157:H7 ATCC 43895 (American Type Culture Collection, Rockville, MD) using a "sandwich test." In this test, 25 μL of bacterial suspension was placed in the center of a swatch, and a second identical swatch was laid upon it, held in place by a sterile weight to insure good contact of the swatches with the inoculum. The bacterial suspensions employed for the tests contained from 10⁶ to 10⁷ colony forming units (CFU), the actual number determined by counting after spread-plating on Trypticase soy agar (Difco Laboratories, Detroit, MI) plates. After contact times of 0.5, 5.0, 10.0, and 30.0 min, the various swatches were placed in sterile conical centrifuge tubes, each containing 5.0 mL of sterile distilled, deionized water, and vortexed for 15 seconds to remove bacteria. Then the swatches were removed, 50 μL of sterile 0.01 M sodium thiosulfate were added to quench any oxidative free chlorine which might have been present, and serial dilutions of the quenched solutions were plated on Trypticase soy agar. The plates were incubated at 37³C for 24 hours and then counted for viable CFU of bacteria.

The biocidal efficacy data for PHS, PHQS (1:1), and PQS for Gram positive S. aureus and Gram negative E. coli O157:H7 are presented in Tables 3 and 4, respectively. The tests were conducted in duplicate in separate experiments. In the first experiment, the swatches coated with PHS contained 0.89% Cl⁺; those coated with PHQS (1:1) contained 0.26% Cl⁺. In the second experiment the corresponding loadings were 0.86% and 0.26%, respectively. The reason why the PHQS (1 :1) swatches contained considerably less Cl⁺ than indicated in Table 2 was that several rinsing cycles were necessary to prevent the elution of quaternary ammonium as determined in the bromophenol blue test. Thus, some hydantoinyl/quaternary ammonium siloxane coating washed away from the surface leading to a lower titrated loading of Cl⁺ for the PHQS (1:1) samples.

Several observations are apparent from Tables 3 and 4 below. All of the biocidal polymer coatings were effective against Gram positive S. aureus including the PQS homopolymer even at the short 30 seconds contact time. The 4.4 log reduction effected by PHQS (1:1) in the 30 seconds contact time in experiment 1 was representative of only 2 CFUs counted, and since a complete inactivation was noted for experiment 2 at this contact time, it can be assumed that this was just an anomalous result. However, it is evident that the coatings containing hydantoinyl siloxane functional groups (PHS and PHQS (1:1)) were much more effective against Gram negative E. coli O157:H7 than was PQS. This has been observed here for PHQS (1:3) as well, so it is evident that copolymers containing at least some chlorinated hydantoinyl functional group are preferred for inactivation of the E. coli O157:H7. This result can be rationalized by consideration of the compositions of the bacterial cells. It is well known that the primary mechanism of action for quaternary ammonium biocides is disruption of the cell membrane, followed by leakage of critical cell components, leading to cell inactivation. (See, for example, Gottenbos, B., et al, Biomaterials 23, 1417-1423, 2002, and references cited therein) On the other hand, the mechanism of action of N-halamine biocides is believed to involve direct transfer of oxidative halogen to the cell where cell inactivation occurs by an oxidation mechanism. Gram negative bacteria, such as E. coli O157:H7, have very complex cell walls which resist penetration by quaternary ammonium cations, but evidently much less so by oxidative chlorine. Gram positive bacteria, such as S. aureus, have much less complex cell walls which are easily penetrated by either quaternary ammonium cations or oxidative chlorine.

It has been demonstrated in these laboratories that the mechanism of action of N-halamine polymer moieties does not involve dissociation of the N-Cl bond in aqueous solution to form "free chlorine" which then acts as the biocidal moiety; the concentration of free chlorine in solution is less than 0.2 mg/L, which is insufficient to cause inactivation of the pathogens in the contact times observed. Furthermore, the polysiloxane copolymer does not solubilize from the cotton surface such that the bacteria are inactivated in solution rather than on the coated cotton surface, as evidenced by the test for quaternary ammonium content in solution discussed above. .

Finally, it should be noted that a quaternary ammonium functional group of trimethyl or triethyl ammonium chloride in PHQS renders the copolymer soluble in water at the IH: IQ level as well. Such copolymers would be less expensive to prepare, but one of the alkyl groups necessarily must be C₁₂ to C_1S (dodecyl to octadecyl) in order for the quaternary ammonium functionality to provide any biocidal activity for the copolymer once oxidative chlorine is expended from the hydantoinyl functional group. Although much of the biocidal activity of the hydantoinyl functionality can be regenerated by simple exposure to dilute bleach, retaining some activity due to the quaternary ammonium functionality would be advantageous, at least for Gram positive bacteria. TABLE 3 The Efficacies of Coated Cotton Swatches A ainst S. aureus

^a Inoculum concentration was 3.33 X lO⁶ CFU; see text for Cl⁺ loadings. ^b Unchlorinated. ^c Chlorinated; see text for loading. ^d Inoculum concentration was 4.76 X 10⁶ CFU; see text for Cl⁺ loadings.

TABLE 4 The Efficacies of Coated Cotton Swatches A ainst E. coli O157:H7

^a Inoculum concentration was 4.18 X 10 CFU; see text for Cl⁺ loadings. ^b Unchlorinated. ^c Chlorinated; see text for loading. ^d Inoculum concentration was 1.00 X 10⁷ CFU; see text for Cl⁺ loadings.

EXAMPLE 2 1. PREPARATION OF POLYG -CHLOROPROPYLSILOXANE)

In a 500 mL flask, 72.14 grams (0.3 mol) of 3-chloropropyltriethoxysilane were mixed with 100 mL of ethanol. While stirring the mixture at ambient temperature, 77.8 grams of concentrated hydrochloric acid were added dropwise. The mixture was refluxed for 5 hours followed by removal of water and ethanol to produce a viscous oil. The oil was then heated at 8CPC under vacuum (about 30 mm Hg) for 15 hours producing 41.0 grams of the expected polymer in about 99% yield. An elemental analysis based upon the expected structure yielded: Calcd. for C₃H₇SiO₂Cl: C, 26.00; H, 5.05; Cl, 25.63. Found: C, 28.67; H, 4.85; Cl, 26.56. ¹H NMR (d₆-DMSO) d 0.76 (2H), 1.79 (2H), 3.33 (IH), 3.60 (2H). 2. PREPARATION OF THE POTASSIUM SALT OF

5.5-DIMETHYLHYD ANTOIN

The potassium salt of 5,5-dimethylhydantoin was prepared according to a procedure similar to that outlined in Example 1 of U.S. Patent No. 6,969,769 reproduced herein below.

A one-liter, three-neck-round-bottom flask was fit with a condenser, dropping funnel, and thermometer. To the flask was added a mixture of 500 mL of ethanol, 64.0 g (0.5 mol) of 5,5-dimethylhydantoin (Acros, Inc.), and 28.0 g (0.5 mol) of potassium hydroxide. The mixture was heated to the boiling point until the solution became clear. Then the solid potassium salt of the 5,5-dimethylhydantoin was isolated by evaporation of the ethanol solvent and the water produced in the reaction under reduced pressure. This salt was dried under vacuum at 6O³C for four days to form the anhydrous potassium salt.

3. PREPARATION OF UNHALOGENATED POL YSILOXANE COPOLYMERS Polysiloxane copolymers can be prepared with different ratios of quaternary ammonium groups and hydantoin groups by simply controlling the ratio of hydantoin and tertiary amine reactants used in a sequential or simultaneous process.

For example, in preparing a polysiloxane copolymer having a 1:1 ratio, 13.5 grams (0.1 mol) of poly(3-chloropropylsiloxane) prepared as described in Section 1 was mixed with 8.3 grams (0.05 mol) of the above described potassium salt of 5,5-dimethylhydantoin in DMF solvent. The mixture was stirred at about IOCPC for 5 hours and the potassium chloride byproduct was removed by filtration. Then 10.65 grams (0.05 mol) of dodecyldimethylamine was added to the DMF solution remaining and the mixture was stirred at 9CPC for 4 hours. The DMF was then removed by vacuum distillation and about 30 grams of ethanol were added to dissolve the gel copolymer product. The solution was added dropwise into 300 mL of diethyl ether with vigorous stirring resulting in the formation of polysiloxane polymers as a white solid that was removed by filtration. Following several washing steps with diethyl ether (ethyl acetate can also be used), the white solid product was dried under vacuum overnight at 5CPC. An elemental analysis for nitrogen content in the product isolated after the first reaction step, a bromophenyl blue/methanol titration as a quaternary ammonium analysis after the second step, and a ¹H NMR spectrum of the final copolymer were consistent with the structure proposed below with about equal amounts of the two functional groups present, presumably as a random copolymer.

In similar fashion, other copolymers were made with mole percents of 75% and 25% for the hydantoin functionality, and the corresponding mole percents for the quaternary ammonium functionality were 25% and 75%. All of these copolymers were soluble in water. For comparison purposes, the homopolymers having only hydantoin and quaternary ammonium functional groups were also prepared.

4. PREPARING BIOCIDAL COTTON

A bath containing a 5 percent by weight aqueous solution of the unhalogenated polysiloxane copolymer prepared as described iri Section 2 (with equal loading of hydantoin and quaternary ammonium functional groups) was prepared. Swatches of Style 400 Bleached 100% Cotton Print Cloth (Testfabrics, Inc.) were soaked in the bath for about 5 minutes and then cured at 9O⁰C for 2 hours. Following the curing process, the swatches were soaked in a 5% solution of Clorox® at ambient temperature for 45 minutes, rinsed with water, and dried at 45⁰C for 45 minutes. An iodometric/thiosulfate titration indicated that the oxidative chlorine loading after this process was 0.274%. Chlorinated swatches, unchlorinated swatches, and control cotton swatches containing no coating were then challenged with Staphylococcus aureus (ATCC 6538) bacterial suspensions (0.5 mL) at a cell density of about 5.2 X 10⁶ CFU (colony forming units)/mL at contact time intervals of 15, 30, and 60 minutes. The samples coated with the N-chlorinated hydantoin functional group gave a complete 6.4 log reduction of the bacteria at all three contact times; contact times less than 15 minutes were not evaluated in this experiment. The samples containing the unchlorinated copolymer coating caused log reductions of 3.3, 3.5, and 3.6 at the contact times of 15, 30, and 60 minutes, respectively, indicating mild bactericidal efficacy due to the presence of the quaternary ammonium functional group. The samples containing the unchlorinated copolymer coating caused log reductions of 0.3, 0.3, and 0.5 at the contact times of 15, 30, and 60 minutes, respectively, indicating very little loss of the bacteria_t on the nonbiocidal control swatches. Thus, the chlorinated cotton swatches possessed good biocidal activity, and since the polysiloxane copolymer can be applied from aqueous solution, the coating material should have advantages over pure hydantoinyl siloxane coating materials that are soluble only in organic or organic/water solutions. Furthermore, polysiloxane copolymers are much more biocidally efficacious than a pure quaternary ammonium siloxane coating.

Examples 1 and 2 demonstrate that hydantoinyl/quaternary ammonium polysiloxane copolymers can be prepared that are adequately soluble in water to be used for coating cotton swatches. The swatches possessed biocidal efficacy against Gram positive S. aureus as a result of the quaternary ammonium functional group alone, as well as with the chlorinated hydantoinyl functional group present (greater than 6 logs within 30 seconds contact). However, for Gram negative E. coϊi O157H:7, the presence of the chlorinated hydantoinyl functional group was necessary to achieve 6 to 7 log inactivation within 1 to 10 minutes contact. Also, it was found that a modified iodometric/thiosulfate titration procedure was needed to analytically determine oxidative chlorine loadings on the cotton swatches. Although the examples focused exclusively on coated cotton, the technology could be extended to any surface to which siloxanes will bind. While illustrative embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention.

Claims

CLAIMSThe embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A polysiloxane copolymer comprising, pendant hydantoin groups and pendant quaternary ammonium groups attached to silicon atoms of the copolymer.

2. The polysiloxane copolymer of Claim 1, wherein the copolymer is water soluble.

3. The polysiloxane copolymer of Claim 1, wherein the mole percent of quaternary ammonium groups is at least 10%.

4. The polysiloxane copolymer of Claim 1, wherein the mole percent of quaternary ammonium groups is at least 25%.

5. The polysiloxane copolymer of Claim 1, wherein the mole percent of quaternary ammonium groups is from 10% to 90% and the mole percent of hydantoin groups is from 10% to 90%.

6. The polysiloxane copolymer of Claim 1, wherein hydantoin functional groups and quaternary ammonium functional groups are attached to the silicon atoms via a Cl to C8 linker alkylene group.

7. The polysiloxane copolymer of Claim 6, wherein the linker alkylene group is a trimethylene group.

8. The polysiloxane copolymer of Claim 1, wherein the hydantoin groups have a chlorine or bromine atom attached to a nitrogen atom.

9. The polysiloxane copolymer of Claim 1, comprising hydroxy groups attached to the silicon atoms.

10. The polysiloxane copolymer of Claim 1, wherein the hydantoin groups and quaternary ammonium groups are randomly attached to the polysiloxane copolymer.

11. The polysiloxane copolymer of Claim 1 , wherein (a) the pendant quaternary ammonium groups attached to silicon atoms have the formula;

(b) the pendant hydantoin groups attached to silicon atoms have the formula;

(c) wherein,

R₁ is a Cl to C20 alkyl group;

R₂ is a Cl to C6 alkyl group;

R₃ is a Cl to C6 alkyl group;

R₄ is a Cl to C4 alkyl group or phenyl group;

R₅ is a Cl to C4 alkyl group or phenyl group; or

R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

L₁ is a Cl to C8 linker alkylene group;

L₂ is a Cl to C8 linker alkylene group;

X is H, Cl, or Br;

An^" is a counteranion; and the mole percent of hydantoin groups is 10% to 90% and the mole percent of quaternary ammonium groups is 10% to 90%.

12. The polysiloxane copolymer of Claim 11, wherein the counteranion An^" is Cl^", Br^", or OH\

13. The polysiloxane copolymer of Claim 1 , comprising the formula:

R₁ is a Cl to C20 alkyl group; R₂ is a Cl to C6 alkyl group; R₃ is a Cl to C6 alkyl group; R₄ is a Cl to C4 alkyl group or phenyl group; R₅ is a Cl to C4 alkyl group or phenyl group; or R₄ and R₅ taken together with the carbon to which they are attached form a spiro-substituted cyclic group;

L₁ is a Cl to C8 linker alkylene group; . L₂ is a Cl to C8 linker alkylene group; X is H, Cl, or Br; An^" is a counteranion; n is a number representing a mole percent of 10% to 90%; and m is a number representing a mole percent of 10% to 90%.

14. The polysiloxane copolymer of Claim 13, wherein the counteranion An^" is Cl^", Br^", or OH^".

15. A modified substrate, comprising a copolymer of Claim 1 attached to the substrate.

16. The modified substrate of Claim 15, wherein the substrate comprises a material having an affinity towards hydroxyl groups to covalently bond to the silicon atoms through ether linkages or be attached through an adhesive interaction.

17. A method of making a polysiloxane copolymer, comprising:

(a) reacting a poly(haloalkyltrialkoxysilane) polymer with an amount of alkali metal salt of a 5,5-dialkylhydantoin to attach hydantoin groups to the polymer;

(b) reacting the poly(haloalkyltrialkoxysilane) polymer with an amount of a tertiary amine to attach quaternary ammonium groups to the polymer; and

(c) isolating the product of the reactions of steps (a) and (b), wherein the product comprises a polysiloxane copolymer having pendant hydantoin groups and pendant quaternary ammonium groups being randomly attached to silicon atoms of the copolymer.

18. The method of Claim 17, wherein the haloalkyltrialkoxysilane is chloropropyltriethoxysilane or chloropropyltrimethoxysilane.

19. The method of Claim 17, wherein the alkali metal is potassium or sodium.

20. The method of Claim 17, wherein the alkali metal salt of 5,5-dialkylhydantoin is the alkali metal salt of 5,5-dimethylhydantoin.

21. The method of Claim 17, wherein the alkali metal salt of 5,5-dialkylhydantoin and the tertiary amine are reacted with the poly(haloalkyltrialkoxysilane) polymer sequentially.

22. The method of Claim 17, wherein the alkali metal salt of 5,5-dialkylhydantoin and the tertiary amine are reacted with the poly(haloalkyltrialkoxysilane) polymer simultaneously.

23. The method of Claim 17, wherein the mole percent of quaternary ammonium groups in the polysiloxane copolymer is 10% to 90%.

24. The method of Claim 17, wherein the mole percent of quaternary ammonium groups in the polysiloxane copolymer is at least 25%.

25. The method of Claim 17, further comprising attaching a chlorine or bromine atom to a nitrogen atom of the hydantoin groups.

26. A method for making a modified substrate, comprising attaching a polymer of Claim 1 to a substrate through hydroxyl groups pendant on the copolymer.

27. The method of Claim 26, further comprising exposing the modified substrate to a source of oxidative chlorine or bromine.

28. A method for making a modified substrate, comprising: reacting monomers of a haloalkyltrialkoxysilane with a substrate and to each other to polymerize the monomers into a polysiloxane polymer and to attach the polysiloxane polymer to the substrate through ether linkages or an adhesive interaction to provide a substrate with an attached polysiloxane polymer having haloalkyl groups; and reacting the haloalkyl groups of the attached polysiloxane polymer with an alkali metal salt of a 5,5-dialkylhydantoin and with a tertiary amine to provide a substrate with an attached polysiloxane copolymer having pendant 5,5-dialkylhydantoin groups and pendant quaternary ammonium groups.

29. A method for making a polysiloxane copolymer, comprising reacting monomers of a (3-alkyl-5,5-dialkylhydantoinyl)trialkoxysilane with monomers of a [3-(trialkylammonium)alkyl]trialkoxysilane to make a polysiloxane copolymer having pendant hydantoin groups and pendant quaternary ammonium groups.

30. The method of Claim 29, wherein the mole precent of hydantoin groups is from 10% to 90% and the mole percent of quaternary ammonium groups is from 10% to 90% in the polysiloxane copolymer.

31. Poly[3-(5,5-dimethylhydantoinylpropyl)siloxane-co-3 dimethyldodecylammoniumpropylsiloxane chloride] .