WO2021107870A1

WO2021107870A1 - Antimicrobial agent, coating formulation, composite surface coating and methods of preparing the same

Info

Publication number: WO2021107870A1
Application number: PCT/SG2020/050688
Authority: WO
Inventors: Yugen Zhang; Jinquan Wang; Shu Wen Diane LIM
Original assignee: Agency For Science, Technology And Research
Priority date: 2019-11-25
Filing date: 2020-11-24
Publication date: 2021-06-03

Abstract

There is provided an antimicrobial agent comprising at least one polymer comprising an optionally substituted heteroaryl amine salt moiety such as an imidazolium salt or an optionally substituted quaternary ammonium cation moiety. The polymer has terminal hydroxyl groups. A coating formulation comprising at least one sol-gel precursor and said antimicrobial agent, as well as a composite surface coating comprising said antimicrobial agent are also provided. Further provided are methods of preparing the antimicrobial agent, composite surface coating and use of the composite surface coating for antimicrobial applications.

Description

Antimicrobial Agent, Coating Formulation, Composite Surface Coating and Methods of Preparing the Same

References to Related Applications

This application claims priority to Singapore application number 10201911115P filed on 25 November 2019, the disclosure of which is hereby incorporated by reference.

Technical Field

The present invention relates to an antimicrobial agent, a coating formulation, a composite surface coating, methods of preparing the same and use of the composite surface coating for antimicrobial applications.

Background Art

Infectious disease and the increasing threat of a worldwide pandemic have emphasized the importance of antibiotics and hygiene. Microbial infection is also one of the most serious concerns for many commercial applications such as medical devices, hospital surfaces, textiles, food packaging, children’s toys, electrical appliances (i.e. mobile phones), and dental surgery equipment. Hospital- acquired infections affect two million people per year in the US alone, with a resultant 90,000 deaths. Creating clean antimicrobial surfaces with long-term stability and activity has tremendous applications spanning almost all aspects of our daily life, from medical devices to construction surfaces. Currently, organic molecular antimicrobial agents, such as triclosan and biguanides, are standard ingredients in consumer care products such as antiseptics, disinfectants and preservatives to inhibit microbial growth for preventing infections. However, these conventional antimicrobial agents may cause serious concern due to their toxicity to environment and potential resistance in microbes. Alcohol-based hand sanitizers and surgical scrubs commonly used in hospital settings may cause skin irritation and dehydration. Bleach detergents are strong oxidants which kill microbes very efficiently. However, they also cause serious environment burden due to an irritating smell and harmful residuals.

Antimicrobial surface coating technologies, when incorporated into commercial products, could reduce the number of infections caused by pathogenic bacteria and would also be extremely advantageous for the healthcare field and food preparation industry. Currently there are three main kinds of antimicrobial materials used in coatings.

The first, and the most widely used, class is based on silver nanoparticles including colloidal silver and nano-sized silver or copper nanoparticles. These antimicrobial agents may also cause metal contamination, resistance development and are not suitable for transparent coatings as they tend to darken or blacken over an extended period.

The second class of antimicrobial agent is based on organic materials and includes antibiotics, antimicrobial peptides, biocides, and antimicrobial polymers. The coating technologies for these antimicrobial agents mainly comprise tethering biocides to the coating matrix or via graft polymerization. The main issues for these coating methods are complex and costly coating process (as is the case for antibiotics and antimicrobial peptides) and limited efficacy against certain bacterial strains. The third class of agent is based on metal oxide nanoparticles including zinc oxide (ZnO), titanium oxide (T1O₂), aluminium oxide (AI₂O₃), etc. However, the antimicrobial efficiency is not very stable and depends on many parameters such as particle size, crystal structure, application environment, and coating components. Therefore, one major challenge that prevents the wide application of antimicrobial coating technology in the public domain is the lack of cheap antimicrobial agents with low toxicity (yet high selectivity and efficiency against a wide range of microbes and superbugs) which can be easily tethered to surfaces. In addition, other challenges include the shortage of technologies that can slowly release antimicrobial reagents from coated surfaces to maintain high activities over long periods and methods that can create surfaces with multiple functions and characteristics, such as antimicrobial, high transparency and ease of cleaning.

Therefore, there is a need to provide an antimicrobial agent, a coating formulation, a composite surface coating and methods of preparing the same that overcome or ameliorate one or more of the disadvantages mentioned above.

Summary

In one aspect, the present disclosure relates to an antimicrobial agent comprising at least one polymer, wherein the polymer comprises repeating units according to formula (I):

Formula (I) wherein L is selected from the group consisting of optionally substituted aryl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted arylalkenyl and optionally substituted arylalkynyl; and

A is selected from an optionally substituted heteroaryl amine salt or an optionally substituted quaternary ammonium cation; and p is an integer of at least 1 ; and wherein said polymer is provided with terminal hydroxyl groups.

In another aspect, the present disclosure relates to a coating formulation comprising at least one sol-gel precursor, a solvent, and the antimicrobial agent as defined herein.

Advantageously, the coating formulation has highly active and long-term antimicrobial activity. Further advantageously, the coating formulation can be easily applied on both hard surfaces and fabrics or textiles to create self-disinfecting materials.

In another aspect, the present disclosure relates to a composite surface coating comprising the antimicrobial agent as defined herein, whereby said coating is provided with terminal silicate groups, dispersed within a sol-gel matrix. Advantageously, the composite surface coating is a thin and highly transparent layer, and is highly active against various microbes. Further advantageously, the composite surface coating is also weather-resistant. The antimicrobial agent can be slowly released from the sol-gel matrix enabling long-term antimicrobial activity.

In another aspect, the present disclosure relates to a method of preparing antimicrobial agent as defined herein, comprising the steps of reacting a polymer with a halogenated benzyl alcohol or a halogenated alkyl alcohol in the presence of an organic solvent to impart terminal hydroxyl tails to the polymer, wherein the polymer comprises repeating units according to formula (I):

A is selected from an optionally substituted heteroaryl amine salt or an optionally substituted quaternary ammonium cation; and p is an integer of at least 1.

In another aspect, the present disclosure relates to a method of preparing the composite surface coating as defined herein comprising the steps of reacting the antimicrobial agent as defined herein with at least one sol-gel precursor in the presence of a solvent to disperse the antimicrobial agent within a polymer matrix to form a sol-gel coating formulation, applying the coating formulation to a substrate and drying the substrate.

In another aspect, the present disclosure relates to use of the composite surface coating as defined herein for antimicrobial applications.

Advantageously, the design of embedding antimicrobial agent into the silicate framework by forming Si-0 bond results in a long term antimicrobial activity of the composite surface coating.

Definitions

The following words and terms used herein shall have the meaning indicated:

The term “composite material”, “composition material” or “composite” is a material made from two or more constituent materials with significantly different physical or chemical properties that, when combined, produce a material with characteristics different from the individual components.

The term "antimicrobial" refers to anything that kills or inhibits the growth of microbes. The term "antimicrobial" can be used to describe a thing or a characteristic of the thing and in this context, refers to the ability to kill or inhibit the growth of microbes. The terms "antimicrobial", "microbicide" and "biocide" are used interchangeably. The term "quarternary ammonium salts" refers to an ammonium salt that contains a quarternary nitrogen cation and a counter ion. The nitrogen cation may be in a ring structure or may be part of a chain structure.

"Aryl" as a group or part of a group to be interpreted broadly denotes (i) an optionally substituted monocyclic, or fused polycyclic, aromatic carbocycle (ring structure having ring atoms that are all carbon) preferably having from 5 to 12 atoms per ring, e.g. 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, wherein the optionally substitution can be di-substitution, or tri substitution. Examples of aryl groups include phenyl, naphthyl, and the like; (ii) an optionally substituted partially saturated bicyclic aromatic carbocyclic moiety in which a phenyl and a Cs- 7 cycloalkyl or C5-7 cycloalkenyl group are fused together to form a cyclic structure, such as tetrahydronaphthyl, indenyl or indanyl. The group may be a terminal group or a bridging group. Typically an aryl group is a C₆-Cis aryl group. The aryl may be optionally substituted with one or more groups as defined under the term "optionally substituted" below. Preferably the groups may include ori/zo-phenylene group, para-phenylene group and meta-phenylene group where it is used interchangeably with o-phenylene group, -phcnylcnc group and m-phenylene group.

"Alkyl" as a group or part of a group refers to a straight or branched aliphatic hydrocarbon group to be interpreted broadly, having from 1 to 16 carbon atoms, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 carbon atoms, preferably a C1-C16 alkyl, C1-C12 alkyl, more preferably a C1-C10 alkyl, most preferably C1-C6 alkyl unless otherwise noted. Examples of suitable straight and branched alkyl substituents include but is not limited to, methyl, ethyl, 1 -propyl, isopropyl, 1 -butyl, 2-butyl, isobutyl, tert-butyl, amyl, 1,2- dime thy lpropyl, 1,1-dimethylpropyl, pentyl, isopentyl, hexyl, 4-methylpentyl, 1- methylpentyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2- dime thy lbutyl, 1,3-dimethylbutyl, 5-methylheptyl, 1-methylheptyl, octyl, nonyl, decyl, undecyl, 2,2,3-trimethyl-undecyl, dodecyl, 2,2-dimethyl-dodecyl, tridecyl, 2-methyl- tridecyl, 2-methyl-tridecyl, tetradecyl, 2-methyl-tetradecyl, pentadecyl, 2-methyl- pentadecyl, hexadecyl, 2-methyl-hexadecyl and the like. The alkyl may be optionally substituted with one or more groups as defined under the term "optionally substituted" below.

“Alkenyl” as a group or part of a group denotes an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched preferably having 2 to 16 carbon atoms, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 carbon atoms, preferably a C2-Ci6alkenyl, C2-Ci2alkenyl, more preferably a C2-Cioalkenyl, most preferably C2-C6alkenyl in the normal chain. The group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonenyl. The group may be a terminal group or a bridging group. The bridging group may be ethenylene or vinylene. The alkenyl may be optionally substituted with one or more groups as defined under the term "optionally substituted" below.

"Alkynyl” as a group or part of a group means an aliphatic hydrocarbon group containing a carbon-carbon triple bond and which may be straight or branched preferably having from 2 to 16 carbon atoms, e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 carbon atoms, preferably a C2-C16 alkynyl, C2-C12 alkynyl, more preferably a C2-C10 alkynyl, most preferably C2-C6 alkynyl in the normal chain. Exemplary structures include, but are not limited to, ethynyl and propynyl. The group may be a terminal group or a bridging group. The alkynyl may be optionally substituted with one or more groups as defined under the term "optionally substituted" below.

“Alkylaryl” refers to an alkyl-aryl group in which alkyl and aryl moieties are as defined herein. Alternatively, “arylalkyl” refers to an aryl-alkyl group in this sequence, in which aryl and alkyl moieties are as defined herein. Preferred alkylaryl groups are C1-C4- alkylaryl having 6 or 10 carbon atoms in the aryl. Preferred arylalkyl groups are aryl-Ci- C4- alkyl having 6 or 10 carbon atoms in the aryl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the aryl group. The alkyl moiety of the alkylaryl or arylalkyl may also be the terminating molecule.

“Arylalkenyl” refers to an alkenyl-aryl group in which alkenyl and aryl moieties are as defined herein. Alternatively, “arylalkenyl” refers to an aryl -alkenyl group in this sequence, in which aryl and alkenyl moieties are as defined herein. Preferred alkenylaryl groups are C2-C6- alkenylaryl having 6 or 10 carbon atoms in the aryl. Preferred arylalkenyl groups are aryl-C2- C₆-alkenyl having 6 or 10 carbon atoms in the aryl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the aryl group. The alkenyl moiety of the alkenylaryl or arylalkenyl may also be the terminating molecule.

“Arylalkynyl” refers to an alkynyl-aryl group in which alkynyl and aryl moieties are as defined herein. Alternatively, “arylalkynyl” refers to an aryl-alkynyl group in this sequence, in which aryl and alkynyl moieties are as defined herein. Preferred alkynylaryl groups are C2-C6- alkynylaryl having 6 or 10 carbon atoms in the aryl. Preferred arylalkynyl groups are aryl-C2- C₆-alkynyl having 6 or 10 carbon atoms in the aryl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the aryl group. The alkynyl moiety of the alkynylaryl or arylalkynyl may also be the terminating molecule.

Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

As used herein, the term "about", in the context of concentrations of components of the formulations, typically means +/- 5% of the stated value, more typically +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range. Certain embodiments may also be described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Detailed Disclosure of Embodiments

Exemplary, non-limiting embodiments of an antimicrobial agent will now be disclosed.

The present disclosure relates to an antimicrobial agent comprising at least one polymer, wherein the polymer comprises repeating units according to formula (I):

A is selected from an optionally substituted heteroaryl amine salt or an optionally substituted quaternary ammonium cation; and p is an integer of at least 1 ; and wherein said polymer is provided with terminal hydroxyl groups. p may be an integer between 1 and 100, between 3 and 100, between 5 and 100, between 10 and 100, between 20 and 100, between 30 and 100, between 40 and 100, between 50 and 100, between 60 and 100, between 70 and 100, between 80 and 100, between 90 and 100, between 1 and 90, between 1 and 80, between 1 and 70, between 1 and 60, between 1 and 50, between 1 and 40, between 1 and 30, between 1 and 20, between 1 and 10, between 1 and 5 or between 1 and 3.

The antimicrobial agent may comprise at least one polymer, wherein the polymer comprises repeating units according to formula (la):

Formula (la) wherein Li, L₂ and L₃ is independently selected from the group consisting of optionally substituted aryl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted arylalkenyl and optionally substituted arylalkynyl; and A2 and A3 is independently an optionally substituted heteroaryl amine salt or an optionally substituted quarternary ammonium cation; and Ai has the structure according to the formula (II):

Formula (II) wherein Ri, R2, R3 and R4 is independently selected from the group consisting of an optionally substituted aryl, optionally substituted alkyl and hydrogen; or any two of Ri, R2, R3 and R4 may be taken to form at least one bridging group; and n is are 0 or integers of at least 1 ; and m, y and z are an integer of at least 1 ; and X is a halogen, and wherein said polymer is provided with terminal hydroxyl groups. m and n may be independently an integer between 1 and 50, between 3 and 50, between 5 and 50, between 10 and 50, between 20 and 50, between 30 and 50, between 40 and 50, between 1 and 40, between 1 and 30, between 1 and 20, between 1 and 10, between 1 and 5 or between 1 and 3. y and z may be independently an integer between 1 and 5. y and z may be independently 1, 2, 3, 4 or 5. y and z may be independently 1.

A2 and A3 may be independently selected from l,4-diazabicyclo-[2.2.2]-octane (DABCO), tetramethylethane- 1,2-diamine (TMED) and 1,4-Dimethylpiperazine (DMP).

Formula (I) may have the general formula (III)

wherein:

R¹¹ and R¹² are independently selected from aryl, arylalkyl, alkylarylalkyl, alkylaryl, alkyl, cycloalkyl, alkenyl or alkynyl, said aryl, alkylaryl, alkylarylalkyl or alkylaryl being optionally substituted by alkyl, alkenyl or alkynyl; each R¹³ is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl; R¹⁴ is selected from hydrogen or aryl, said aryl being optionally substituted by alkyl, alkenyl or alkynyl;

- is either a single bond or a double bond; b is an integer selected from 0 to 3; a is an integer selected from 0 to 3; c is an integer selected from 2 to 50; and X is a counterion.

In the compound of general formula (III), R¹¹ may be selected from aryl, alkylaryl or alkylarylalkyl. R¹¹ may be aryl selected from phenyl. R¹¹ may be arylalkyl selected from arylCi-₆, such as phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl or phenylhexyl. R¹¹ may be alkylarylalkyl selected from Ci-₆arylCi-₆, such as methylphenylmethyl, methylphenylethyl, methylphenylpropyyl, methylphenylbutyl, methylphenylpentyl, methylphenylhexyl, ethylphenylmethyl, ethylphenylethyl, ethylphenylpropyyl, ethylphenylbutyl, ethylphenylpentyl, ethylphenylhexyl, propylphenylmethyl, propylphenylethyl, propylphenylpropyyl, propylphenylbutyl, propylphenylpentyl, propylphenylhexyl, butylphenylmethyl, butylphenylethyl, butylphenylpropyyl, butylphenylbutyl, butylphenylpentyl, butylphenylhexyl, pentylphenylmethyl, pentylphenylethyl, pentylphenylpropyyl, pentylphenylbutyl, pentylphenylpentyl, pentylphenylhexyl, hexylphenylmethyl, hexylphenylethyl, hexylphenylpropyyl, hexylphenylbutyl, hexylphenylpentyl or hexylphenylhexyl. Where R 11 ; IS an aryl, arylalkyl or alkylarylalkyl, the aryl, arylalkyl or alkylarylalkyl may be substituted at the ortho position or at the meta position. Hence, where R¹¹ is phenyl, phenylmethyl or methylphenylmethyl, the phenyl, phenylmethyl or methylphenylmethyl may be substituted at the ortho position or at the meta position.

In the compound of general formula (III), R¹² may be selected from aryl, alkylaryl or alkylarylalkyl. R¹² may be aryl selected from phenyl. R¹² may be arylalkyl selected from arylCi-₆, such as phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl or phenylhexyl. R¹² may be alkylarylalkyl selected from Ci-₆arylCi-₆, such as methylphenylmethyl, methylphenylethyl, methylphenylpropyyl, methylphenylbutyl, methylphenylpentyl, methylphenylhexyl, ethylphenylmethyl, ethylphenylethyl , ethylphenylpropyyl, ethylphenylbutyl, ethylphenylpentyl, ethylphenylhexyl, propylphenylmethyl, propylphenylethyl, propylphenylpropyyl, propylphenylbutyl, propylphenylpentyl, propylphenylhexyl, butylphenylmethyl, butylphenylethyl, butylphenylpropyyl, butylphenylbutyl, butylphenylpentyl, butylphenylhexyl, pentylphenylmethyl, pentylphenylethyl, pentylphenylpropyyl, pentylphenylbutyl, pentylphenylpentyl, pentylphenylhexyl, hexylphenylmethyl, hexylphenylethyl, hexylphenylpropyyl, hexylphenylbutyl, hexylphenylpentyl or hexylphenylhexyl. Where R¹² is an aryl, arylalkyl or alkylarylalkyl, the aryl, arylalkyl or alkylarylalkyl may be substituted at the ortho position or at the meta position. Hence, where R¹² is phenyl, phenylmethyl or methylphenylmethyl, the phenyl, phenylmethyl or methylphenylmethyl may be substituted at the ortho position or at the meta position.

R¹² may be an alkyl or an alkenyl group. R¹² may be Ci-₆-alkyl or C2-6-alkenyl. R¹² may be selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, ethylene, propylene, butylene, pentylene or hexylene. The hexylene may be 3-hexenyl.

In the compound of general formula (III), R¹³ may be hydrogen. In the compound of general formula (III), R¹⁴ may be hydrogen or aryl such as phenyl.

In the compound of general formula (III), X may be a halide selected from the group consisting of fluoride, iodide, bromide and chloride.

The compound of formula (III) may have a molecular weight in the range of about 1000 to about 3000, about 1000 to about 2000, about 1300 to about 1400, about 2000 to about 3000, about 2500 to about 3000 or about 2700 to about 2800. The molecular weight of the compound may be about 1300 or about 2700.

The compound of formula (III) may be selected from formula (Ilia).

Formula (Ilia) wherein c is an integer selected from 2 to 50. c may be preferably an integer selected from 3 to 5.

In the compound of general formula (I), A may be of the following structure:

wherein R¹, R², R³ and R⁴ may be independently selected from an optionally substituted alkyl, or any two of R¹, R², R³ and R⁴ may be taken together to form at least one bridging group, and x and y may independently be an integer of at least 1.

The optionally substituted alkyl may be optionally substituted Ci-isalkyl group, preferably optionally substituted Ci-i2alkyl group or more preferably, optionally substituted Ci-₆alkyl group.

The any two of R¹, R², R³ and R⁴ may be taken together to form at least one bridging group. R¹ and R² may be taken together to form at least one bridging group. R³ and R⁴ may be taken together to form at least one bridging group. The bridging group may be C₂ to C₁₀ bridging group, preferably C₂ to C₅ bridging group or more preferably an ethenylene group. The bridging group may be optionally substituted.

The y and z may independently be an integer of at least 1 or at least between 1 to 10, between 1 to 5, from 1, 2, 3, 4 or 5, or more preferably 1.

A may be selected from the group consisting of the following structures:

In the polymer having the formula (I), the molar ratio between A and L may be in the range of 1:5 and 5:1, in the range of 1:4 and 5:1, in the range of 1:3 and 5:1, in the range of 1:2 and 5:1, in the range of 1:1 and 5:1, in the range of 2:1 and 5:1, in the range of 3:1 and 5:1, in the range of 4:1 and 5:1, in the range of 1:5 and 4:1, in the range of 1:5 and 3:1, in the range of 1:5 and 2:1 or in the range of 1:5 and 1:1, in the range of 1:5 and 1:2, in the range of 1:5 and 1:3 or in the range of 1:5 and 1:4.

Formula (I) may be selected from the group consisting of the following structures

The polymer of Formula (I) may be copolymers formed by the two or more repeating units of the following structures. The total number of the repeating units may be an integer between 1 and 100, between 3 and 100, between 5 and 100, between 10 and 100, between 20 and 100, between 30 and 100, between 40 and 100, between 50 and 100, between 60 and 100, between 70 and 100, between 80 and 100, between 90 and 100, between 1 and 90, between 1 and 80, between 1 and 70, between 1 and 60, between 1 and 50, between 1 and 40, between 1 and 30, between 1 and 20, between 1 and 10, between 1 and 5 or between 1 and 3.

, and

The antimicrobial agent may comprise one or more hydroxyl groups.

Exemplary, non-limiting embodiments of a coating formulation will now be disclosed.

The present disclosure relates to a coating formulation comprising at least one sol-gel precursor, a solvent, and the antimicrobial agent as defined herein.

The sol-gel precursor may be an alkyl silicate, an alkyl alkoxy silicate, an aryl alkoxyl silicate. The sol-gel precursor may be selected from the group consisting of tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), methyl trimethoxysilane (MTMS), phenyltrimethoxysilane (PTMS) and dimethyl dimethoxysilane (DMDMS) as well as methacryloxypropyltrimethoxysilane (MPTMS) and other non-saturated silanes. The amount of the sol-gel precursor may be in the range of about 2 wt% to about 20 wt%, about 3 wt% to about 20 wt%, about 5 wt% to about 20 wt%, about 8 wt% to about 20 wt%, about 10 wt% to about 20 wt%, about 15 wt% to about 20 wt%, about 2 wt% to about 15 wt%, about 2 wt% to about 10 wt%, about 2 wt% to about 8 wt%, about 2 wt% to about 3 wt%, about 2 wt% to about 3 wt% based on the weight of the coating formulation.

The antimicrobial agent may comprise at least one polymer, the polymer having Formula (I) or Formula (la).

The amount of the antimicrobial agent may be in the range of about 1 wt% to about 10 wt%, about 3 wt% to about 10 wt%, about 5 wt% to about 10 wt%, about 7 wt% to about 10 wt%, about 8 wt% to about 10 wt%, about 1 wt% to about 8 wt%, about 1 wt% to about 7 wt%, about 1 wt% to about 5 wt%, about 1 wt% to about 3 wt% based on the weight of the coating formulation.

The solvent may be used to adjust the hydrophobicity of the coating formulation. The solvent may be pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, dichloromethane (DCM), tetrahydrofuran (THF), acetone, dimethylformamide (DMF), acetonitrile (MeCN), dimethyl sulfoxide (DMSO), formic acid, n- butanol, isopropyl alcohol (IPA), ethanol, water or their mixtures thereof. The solvent may preferably be a mixture of ethanol and water.

The amount of the solvent may be in the range of about 20 wt% to about 90 wt%, about 30 wt% to about 90 wt%, about 40 wt% to about 90 wt%, about 50 wt% to about 90 wt%, about 60 wt% to about 90 wt%, about 70 wt% to about 90 wt%, about 80 wt% to about 90 wt%, about 20 wt% to about 80 wt%, about 20 wt% to about 70 wt%, about 20 wt% to about 60 wt%, about 20 wt% to about 50 wt%, about 20 wt% to about 40 wt%, about 20 wt% to about 30 wt% based on the weight of the coating formulation.

The coating formulation may further comprise an acid or a base to adjust pH value.

The pH value of the coating formulation may be in the range of about 2 to about 10, about 3 to about 810, about 4 to about 10, about 5 to about 10, about 6 to about 10, about 7 to about 10, about 8 to about 10, about 9 to about 10,. about 2 to about 9, about 2 to about 8, about 2 to about 7, about 2 to about 6, about 2 to about 5, about 2 to about 4 or about 2 to about 3.

The amount of the acid or the base may be in the range of about 0 to 1 wt%, about 0.1 wt% to 1 wt%, about 0.3 wt% to 1 wt%, about 0.5 wt% to 1 wt%, about 0.7 wt% to 1 wt%, about 0.8 wt% to 1 wt%, about 0 to 0.8 wt%, about 0 to 0.7 wt%, about 0 to 0.5 wt%, about 0 to 0.3 wt%, about 0 to 0.1 wt% based on the weight of the coating formulation.

The coating formulation may further comprise surfactants to adjust hydrophobicity.

The coating formulation may further comprise metal alkoxides such as aluminum alkoxide, zinc alkoxide and zirconium alkoxide as well as metal nanoparticles.

The metal nanoparticles may be selected from zinc, aluminium, iron, cobalt, nickel, copper, manganese, chromium, vanadium, germanium, or tin; or mixtures and/or alloys thereof. The coating formulation may further comprise fluorinated silane surfactants, which may be used to impart hydrophobicity.

The present disclosure relates to a composite surface coating comprising the antimicrobial agent as defined herein, whereby said coating is provided with terminal silicate groups, dispersed within a sol-gel matrix.

The composite surface coating could be very thin. The thickness of the composite surface coating may be in the range of about 50 nm to about 1 mm, about 100 nm to about 1 mm, about 200 nm to about 1 mm, about 500 nm to about 1 mm, about 1 pm to about 1 mm, about 10 pm to about 1 mm, about 100 pm to about 1 mm, about 200 pm to about 1 mm, about 500 pm to about 1 mm, about 800 pm to about 1 mm, about 50 nm to about 800 pm, about 50 nm to about 500 pm, about 50 nm to about 200 pm, about 50 nm to about 100 pm, about 50 nm to about 10 pm, about 50 nm to about 1 pm, about 50 nm to about 500 nm, about 50 nm to about 200 nm or about 50 nm to about 100 nm.

Advantageously, when the coating formulation as defined herein is applied onto surfaces to form the composite surface coating as defined herein, the antimicrobial agent can be slowly released from the framework effecting biocidal property.

The present disclosure relates to a method of preparing antimicrobial agent as defined herein, comprising the steps of reacting a polymer with a halogenated benzyl alcohol or a halogenated alkyl alcohol in the presence of an organic solvent to impart terminal hydroxyl tails to the polymer wherein the polymer comprises repeating units according to formula (I):

Formula (I) may have the general formula (III) wherein:

R¹¹ and R¹² are independently selected from aryl, arylalkyl, alkylarylalkyl, alkylaryl, alkyl, cycloalkyl, alkenyl or alkynyl, said aryl, alkylaryl, alkylarylalkyl or alkylaryl being optionally substituted by alkyl, alkenyl or alkynyl; each R¹³ is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl;

R¹⁴ is selected from hydrogen or aryl, said aryl being optionally substituted by alkyl, alkenyl or alkynyl;

In the compound of general formula (I), A may be of the following structure:

The halogenated benzyl alcohol may be a para-halogenated benzyl alcohol, a meta-halogenated benzyl alcohol or an ortho-halogenated benzyl alcohol. The para-halogenated benzyl alcohol may be a para-halogenated-methyl benzyl alcohol, a para-halogenated-ethyl benzyl alcohol, a para-halogenated-propyl benzyl alcohol, a para-halogenated-butyl benzyl alcohol, a para- halogenated-pentyl benzyl alcohol, a para-halogenated-hexyl benzyl alcohol, a para- halogenated-heptyl benzyl alcohol, a para-halogenated-octyl benzyl alcohol, a para- halogenated-nonyl benzyl alcohol, a para-halogenated-decyl benzyl alcohol, a para- halogenated-undecyl benzyl alcohol or a para-halogenated-dodecyl benzyl alcohol. The para- halogenated-methyl benzyl alcohol may be selected from the group consisting of 4- (chloromethyl)benzyl alcohol, 4-(bromomethyl)benzyl alcohol, and 4-(fluoromethyl)benzyl alcohol.

The halogenated alkyl alcohol may have the formula X-(CH2)_n-OH, where n is an integer between 1 to 16 and X is chlorine, bromine or fluorine. The alkyl may be linear, branched or cyclic. The halogenated alkyl alcohol may be selected from the group consisting of 2- chloroethanol, 3 -chloro-1 -propanol, 2-chloro-l -propanol, 4-chloro-l -butanol, 5-chloro-l- pentanol, 6-chloro-l-hexanol, 4-chloro-l -hexanol, 7-chloro-l-heptanol, 8-chloro-l-octanol, 9- chloro-l-nonanol, 10-chloro-l-decanol, 11-chloro-l-undecanol, 12-chloro-l-dodecanol, 16- chloro-l-hexadecanol, 2-bromoethanol, 3 -bromo-1 -propanol, 2-bromo-l -propanol, 4-bromo- 1-butanol, 5-bromo-l-pentanol, 6-bromo-l -hexanol, 4-bromo-l -hexanol, 7-bromo-l-heptanol, 8-bromo-l-octanol, 9-bromo-l-nonanol, 10-bromo-l-decanol, 11-bromo-l-undecanol, 12- bromo-l-dodecanol, 16-bromo-l-hexadecanol and mixtures thereof.

The polymer of the antimicrobial agent and the halogenated benzyl alcohol may be mixed with a molar ratio from 1: 2 to 1:5. The polymer of the antimicrobial agent and the halogenated benzyl alcohol may be mixed with a molar ratio from 1: 2.5 to 1:4. The halogenated benzyl alcohol may be para-halogenated-methyl benzyl alcohol.

The reacting step may be conducted at a temperature of about 65 to about 100 °C, about 70 to about 100 °C, about 75 to about 100 °C, about 80 to about 100 °C, about 85 to about 100 °C, about 90 to about 100 °C, about 95 to about 100 °C, about 65 to about 95 °C, about 65 to about 90 °C, about 65 to about 85 °C, about 65 to about 80 °C, about 65 to about 75 °C, or about 65 to about 70 °C.

The reacting step may be conducted for about 1 to about 24 hours, about 2 to about 24 hours, about 4 to about 24 hours, about 6 to about 24 hours, about 8 to about 24 hours, about 10 to about 24 hours, about 15 to about 24 hours, about 20 to about 24 hours, about 1 to about 20 hours, about 1 to about 15 hours, about 1 to about 10 hours, about 1 to about 8 hours, about 1 to about 6 hours, about 1 to about 4 hours or about 1 to about 2 hours.

The organic solvent may be selected from the group comprising of ethanol, tetrahydrofuran (THF), acetonitrile, N-N-dimethylformamide (DMF), and other common solvents.

The present disclosure relates to a method of preparing the composite surface coating as defined herein comprising the steps of reacting the antimicrobial agent as defined herein with at least one sol-gel precursor in the presence of a solvent to disperse the antimicrobial agent within a polymer matrix to form a sol-gel coating formulation, applying the coating formulation to a substrate and drying the substrate.

The substrate may be plastic such as polycarbonate, polypropylene, stainless steel, glass and ceramics.

The sol-gel formulation, when dried, then forms a composite surface coating on the substrate.

The present disclosure relates to use of the composite surface coating as defined herein for antimicrobial applications.

The use of composite surface coating may have an antimicrobial effect against microbes such as bacteria, virus or fungi. Some exemplary microbes that can be inactivated or killed by the composite surface may be, but not limited to S. aureus, E. coli, P. aeruginosa, or C. albicans.

The use of composite surface coating may achieve antimicrobial property with more than six log reductions (JIS 2801 method) when the coating is reused for the fourth time. For the composite surface coating on glass under sponge brushing test, the antimicrobial activity after 10000 times brushing remains about the same as the initial activity.

Brief Description of Drawings

The accompanying drawings illustrate a disclosed embodiment and serves to explain the principles of the disclosed embodiment. It is to be understood, however, that the drawings are designed for purposes of illustration only, and not as a definition of the limits of the invention.

Fig· 1

[Fig. 1] is a schematic diagram showing a working mechanism of the composite surface coating with the antimicrobial agent.

Fig. 2

[Fig. 2] is a schematic diagram showing the synthesis of antimicrobial ingredient 2A.

Fig. 3

[Fig. 3] is a schematic diagram showing the synthesis of antimicrobial ingredient 2B.

Fig. 4

[Fig. 4] shows antimicrobial properties of the composite surface coating with more than six log reductions of colony-forming unit (CFU) (JIS 2801 method, 2.5 cm x 2.5 cm glass, 100 pL of microbe solution was plated onto each sample) (a) E. coli, (b) E. coli. (surface was reused under testing conditions for the fourth time), (c) S. aureus, (d) C. albicans. In this figure, the bar on the left of each incubation time corresponds to the legend “Blank” (sample without antimicrobial coating) while the bar on the right of each incubation time corresponds to the legend “GEL” (sample with antimicrobial coating). The asterisk sign represents the value is so small that is not visible on the graph based on the scale of the y axis.

Fig. 5

[Fig. 5] shows killing dynamics of the composite surface coating (JIS 2801 method, 2.5 cm x 2.5 cm glass, 100 pL of microbe solution was plated onto each sample) (a) 10 minutes, (b) lhour. In this figure, the bar on the left of each incubation time corresponds to the legend “Blank” (sample without antimicrobial coating) while the bar on the right of each incubation time corresponds to the legend “GEL” (sample with antimicrobial coating). The asterisk sign represents the value is so small that is not visible on the graph based on the scale of the y axis.

Fig. 6

[Fig. 6] shows antimicrobial properties of the composite surface coating on different substrates (JIS 2801 method, 2.5 cm x 2.5 cm glass, 100 pi of microbe solution was plated onto each samples) (a) Plastic made from polycarbonate, (b) Plastic made from polypropylene, (c) Stainless steel, (d) Ceramics. In this figure, the bar on the left of each incubation time corresponds to the legend “Blank” (sample without antimicrobial coating) while the bar on the right of each incubation time corresponds to the legend “GEL” (sample with antimicrobial coating). The asterisk sign represents the value is so small that is not visible on the graph based on the scale of the y axis.

Fig. 7

[Fig. 7] shows antimicrobial properties of the composite surface coating which has more than 8 log reduction after 10000 times brushing (dry). (JIS 2801 method, 2.5 cm x 2.5 cm glass, 100 mΐ of microbe solution was plated onto each sample). In this figure, the bar on the left of each incubation time corresponds to the legend “Blank” (sample without antimicrobial coating), the bar in the middle of each incubation time corresponds to the legend “GEL on glass before” (sample with antimicrobial coating before brushing), and the bar on the right of each incubation time corresponds to the legend “GEL on glass after” (sample with antimicrobial coating after brushing). The asterisk sign represents the value is so small that is not visible on the graph based on the scale of the y axis.

Detailed Description of Drawings

As shown in Fig. 1, a schematic diagram showing working mechanism of the composite surface coating with the antimicrobial agent. It is a sol-gel based formulation comprising sol-gel precursors 100 and antimicrobial agent 102 which are functionalised with hydroxyl ending groups. When the solution is applied onto surfaces, there will be a framework including both silicate and antimicrobial agent 102 formed on the surface. The layer formed is very thin. Antimicrobial agent 102 will be slowly released from the framework under wet conditions, whereupon it will play the role of a microbicide.

Examples

Non-limiting examples of the invention will be further described in greater detail by reference to specific Examples, which should not be construed as in any way limiting the scope of the invention.

Example 1: Synthesis of Antimicrobial Agent 2A

As shown in Fig. 2, antimicrobial agent 2A was prepared by the reaction of compound 200 and 202. For synthesizing compound 200, sodium hydroxide (NaOH, 440 mg, 11 mmol, purchased from Aldrich Singapore) was added to a N,N'-dimethyl formamide (DMF, purchased from Aldrich Singapore) solution of imidazole (680 mg, 10 mmol, purchased from Aldrich Singapore), and the resulting suspension was stirred at room temperature for 2 hours. Following which, a,a'-dichloro-a-xylene (5 mmol, purchased from Aldrich Singapore) was added to the residue. The resulting solution was stirred at room temperature for another 4 hours. The solvent was removed under vacuum. The product was extracted with dichloromethane (DCM, purchased from Aldrich Singapore), and the intermediate product as shown below was obtained in quantitative yield after removing the solvent.

Compound 200 was prepared from the condensation reaction intermediate product with 1,4- dibromobutylene (purchased from Aldrich Singapore) in tetrahydrofuran (THF, purchased from Aldrich Singapore). The intermediate product (238 mg, 1 mmol) was added to a THF solution (10 L) of 1,4-dibromobutylene (214 mg, 1 mmol). The resulting solution was stirred at 90°C for 4 hours. The reaction mixture was cooled, and filtered to remove the liquid component. The solid was washed with DMF and with THF, and then dried under vacuum. Compound 200 was produced as a white powder. A mixture of 202 (4 g, 25.5 mmol) and 200 (20 g, about 8 mmol) in absolute ethanol (100 mL) was warmed to 65 °C with stirring. After 3 hours, the solution was cooled and THF (400 mL) was added. The white precipitate formed was allowed to settle to the bottom of the beaker/bottle before the supernatant was decanted. The solids were further washed with THF (200 mL), then dried at 90 °C at 20 mbar over 16 hours. Compound 2A was obtained as hygroscopic white solids (18.1 g, 87%).

Example 2: Synthesis of Antimicrobial Agent 2B

As shown in Fig. 3, antimicrobial agent 2B was prepared by a two steps procedure. 1,4- diazabicyclo-[2.2.2]-octane (DABCO) 300, tetramethylethane- 1,2 -diamine (TMEDA) 302 and -xylylcnc dibromide 304 (with molar ratios m : n : (m+n) as shown in the table below) were mixed in THF. The mixture was stirred at 65 °C for 16 hours. Product 306 was isolated by recrystallization in good yield. Compounds 306 and [4-(chloromethyl)phenyl]methanol 202 (molar ratio 1 : 2 to 1 : 5) mixed in solvent (ethanol, THF, DMF or other common solvent). The mixture was stirred at 65 to 100 °C for 1 to 24 hours. Product 2B was isolated by recrystallization in quantitative yield. Experiment 3 was also conducted in acetonitrile solvent at 85 °C over 16 hours.

20 g scale synthesis of 2B in ethanol: p- ylylene dibromide 304 (13.2 g, 50 mmol) was added in one portion to a solution of 1,4- diazabicyclo-[2.2.2]-octane (DABCO) 300 (1.12 g, 10 mmol) and tetramethylethane- 1,2- diamine (TMEDA) 302 (7.2 mL, 48 mmol) in absolute ethanol (120 mL) at 75 °C. The mixture was stirred at 75°C for 4 hours. [4-(chloromethyl)phenyl]methanol (202) (2.1 g, 13.4 mmol) was added and the mixture stirred at 75 °C for a further 2 hours (or overnight). THF (120 mL) was added, and the resulting mixture was cooled to room temperature. The precipitated white solids were collected by filtration through a Buchner funnel lined with filter paper and rinsed with THF (2 x 30 mL). The solid residue was collected and dried at 90 °C at 20 mbar over 16 h. 2B was obtained as a hygroscopic white powder (19.0 g, 89%).

For the 20 g scale synthesis, the reaction was conducted as a ‘two-step one-pot’ reaction (compound 306 was not isolated before addition of 202) as opposed to the procedure where it was carried out in two separate steps (compound 306 was isolated before subsequent reaction with 202). To accommodate the ‘two-step one-pot’ sequence used for the 20 g scale synthesis, additional TMEDA (48 mmol, as opposed to 40 mmol) was added to ensure that compound 306 had the correct diamine end groups before addition of 202 into the same reaction mixture. Example 3: Antimicrobial Activities of Compounds

Minimum Inhibitory Concentration

Staphylococcus aureus (ATCC 6538, Gram-positive), Escherichia coli (ATCC 8739, Gram negative), Pseudomonas aeruginosa (ATCC 9027, Gram-negative), and Candida albicans (ATCC 10231, fungus) were purchased from ATCC (U.S.A) and used as representative microorganisms to challenge the antimicrobial functions of the oligomers. All bacteria were frozen at -80 °C, and were grown overnight at 37 °C in Mueller Hinton Broth (MHB, BD Singapore) prior to experiments. Fungus was grown overnight at 22 °C in Yeast Mold Broth (YMB, BD Singapore). Subsamples of these cultures were grown for a further 3 h and diluted to give an optical density (O.D.) value of 0.07 at 600 nm (OD600 = 0.07), corresponding to 1.5xl0⁸ CFU mL ¹ for bacteria and 3xl0⁶ CFU mL ¹ for fungus (McFarland’s Standard 0.5; confirmed by plate counts).

The polymers were dissolved in MHB at a concentration of 4 mg mL ¹ and the minimal inhibitory concentrations (MICs) were determined by microdilution assay. Bacterial solutions (100 pL, 1 x 10⁶ CFU mL ¹) were mixed with 100 pL of oligomer solutions (normally ranging from 4 mg mL ¹ to 2 pg mL ¹ in serial two-fold dilutions) in each well of the 96-well plate. The plates were incubated at 37 °C for 24 h with constant shaking speed at 300 rpm. The MIC measurement against Candida albicans is similar to bacteria except that the fungus solution is ~10⁴ CFU mL ¹ in YMB and the plates were incubated at room temperature.

The MICs were taken as the concentration of the materials at which no obvious microbial growth was observed. Medium solution containing microbial cells alone were used as control (100% microbial growth). The assay was performed in four replicates and the experiments were repeated at least two times.

The antimicrobial activities of new compounds 2A, 306, 2B were evaluated against four clinically relevant microbes: S. aureus, E. coli, P. aeruginosa, and C. albicans. Their minimum inhibitory concentrations (MICs) against the four microbes are presented in Table 1. All the compounds exhibited good antimicrobial activity.

Table 1. Antimicrobial activity (MIC, pg/ml ¹).

^a MIC tested against 10⁸ CFU mL ¹ of bacteria or 10⁶CFU mL ¹ of fungi. E. C. (E. coli), S. A. (S. aureus), P. A. (P. aeruginosa), C. A. (C. albicans). ^b MIC tested against 10⁵ CFU mL ¹ of bacteria or 10³ CFU mL ¹ of fungi. E. C. (E. coli), S. A. (S. aureus), P. A. (P. aeruginosa), C. A. (C. albicans). Example 4: Antimicrobial Activities of Surface Coating

JIS killing efficacy testing

The tested bacteria were suspended in 5 mL of respective nutrient broth and adjusted to ODeoo = 0.07. The solution was further diluted 100 times for antibacterial testing. In order to cover the surface, 150 pL of cell suspensions was placed on the surfaces. After incubation at 37 °C with the surfaces, the respective cell suspensions were washed and diluted, and each dilution spread on two nutrient agar plates. Resulting colonies were then counted using standard plate counts techniques, and the number of colony forming units per mL was calculated. The number of colony forming units was assumed to be equivalent to the number of viable cells in suspension.

Antimicrobial Coating for Different Microbes

Tetraethyl orthosilicate (TEOS) (2-20 wt%), antimicrobial ingredient 2A (1-5 wt%), water (10-40 wt%), ethanol (30-70 wt%), hydrochloric acid (0-0.5 wt%) were mixed to obtain a solution. The solution was applied on surfaces, such as glass, metal, wood, plastic, textile, etc, by spraying or mopping. After the coating was dried, the antimicrobial property of the coated surface was evaluated by using JIS 2801 method. As shown in Fig. 4, all antimicrobial coatings showed excellent antimicrobial properties for E. coli, S. aureus, and C. albicans. The antimicrobial effect was maintained after the surface was reused under the testing conditions for the fourth time, which indicates that the antimicrobial effect of the coating was stable after repeated washing. After each test, the sample was rinsed with water and ethanol.

Killing Dynamics for Antimicrobial Coating

Tetraethyl orthosilicate (TEOS) (2-20 wt%), antimicrobial ingredient 2B (1-5 wt%), water (30- 70 wt%), ethanol (20-50 wt%), and hydrochloric acid (0-0.5%) were mixed to obtain a solution. The solution was applied on surfaces, such as glass, metal, wood, plastics, textile by spraying or mopping. After the coating was dried, the antimicrobial property of the coated surface was evaluated by using JIS 2801 method. As shown in Fig. 5, the antimicrobial coating started to show antimicrobial effect after 10 minutes. The antimicrobial effect can reach more than six log reductions after 1 hour.

Antimicrobial Coatings for Different Coated Surface.

Tetraethyl orthosilicate (TEOS) (2-20wt%)„ antimicrobial ingredient 2A(l-5 wt%), water(30 to 70 wt%), ethanol (20-50 wt%), and hydrochloric acid (0-0.5%) were mixed to obtain a solution. The solution was applied on glass surface by spraying or mopping. After the coating was dried, the antimicrobial property of the coated surface was evaluated by using JIS 2801 method. As shown in Fig. 6, the antimicrobial coatings showed excellent antimicrobial properties for all surfaces include plastic made from polycarbonate, plastic made from polypropylene, stainless steel, and ceramics.

Durability and Long Term effect

Tetraethyl orthosilicate (TEOS) (2-20wt%)„ antimicrobial ingredient 2A(l-5 wt%), water(30 to 70 wt%), ethanol (20-50 wt%), and hydrochloric acid (0-0.5%) were mixed to obtain a solution. The solution was applied on glass surface by spraying or mopping. After the coating was dried, the antimicrobial property of the coated surface was evaluated by using JIS 2801 method. For the composite surface coating on glass under sponge brushing test as shown in Fig. 7, the antimicrobial activity after 10000 times brushing remains about the same as the initial activity.

Industrial Applicability

In the present disclosure, the antimicrobial agent, the coating formulation and the composite surface coating as described herein may be used for antimicrobial applications. The coating formulation is easy to apply and the composite surface coating is easy to clean, highly transparent and highly active. The coating can also be applied on both hard surfaces and fabrics or textiles to create long term self-disinfecting materials.

It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

Claims

1. An antimicrobial agent comprising at least one polymer, wherein the polymer comprises repeating units according to formula (I):

2. The antimicrobial agent according to claim 1, wherein p is an integer between 1 and

100.

3. The antimicrobial agent according to claim 1 or 2, wherein the polymer comprises repeating units according to formula (la):

Formula (la) wherein Li, L₂ and L₃ is independently selected from the group consisting of optionally substituted aryl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted arylalkenyl and optionally substituted arylalkynyl; and

A2 and A3 is independently an optionally substituted heteroaryl amine salt or an optionally substituted quarternary ammonium cation; and

Ai has the structure according to the formula (II):

wherein Ri, R₂, R₃ and R₄ is independently selected from the group consisting of an optionally substituted aryl, optionally substituted alkyl and hydrogen; or any two of Ri, R₂, R₃ and R4 may be taken to form at least one bridging group; and n is 0 or integers of at least 1 ; and m, y and z are an integer of at least 1 ; and

X is a halogen, and wherein said polymer is provided with terminal hydroxyl groups.

4. The antimicrobial agent according to claim 3, wherein m and n are independently an integer between 1 and 50.

5. The antimicrobial agent according to claim 3 or 4, wherein y and z are independently an integer between 1 and 5

6. The antimicrobial agent according to claim 5, wherein y and z are independently 1.

7. The antimicrobial agent according to any one of claims 3 to 6, wherein A2 and A3 are independently selected from the group consisting of l,4-diazabicyclo-[2.2.2]-octane (DABCO), tetramethylethane-1, 2-diamine (TMED) and 1,4-Dimethylpiperazine (DMP).

8. A coating formulation comprising at least one sol-gel precursor, a solvent, and the antimicrobial agent according to claims 1 to 7.

9. The coating formulation according to claim 8, wherein the sol-gel precursor is an alkyl silicate, an alkyl alkoxy silicate, or an aryl alkoxyl silicate.

10. The coating formulation according to claim 8 or 9, wherein the sol-gel precursor is selected from the group consisting of tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), methyl trimethoxysilane (MTMS), phenyltrimethoxysilane (PTMS), dimethyl dimethoxysilane (DMDMS) and methacryloxypropyltrimethoxy silane (MPTMS).

11. The coating formulation according to any one of claims 8 to 10, further comprising an acid or a base for adjusting pH value of the coating formulation.

12. The coating formulation according to any one of claims 8 to 11, wherein the pH value of the coating formulation is in the range of 2 to 10.

13. The coating formulation according to any one of claims 8 to 12, further comprising surfactants for adjusting hydrophobicity.

14. The coating formulation according to claim 13, wherein the solvent is pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, dichloromethane (DCM), tetrahydrofuran (THF), acetone, dimethylformamide (DMF), acetonitrile (MeCN), dimethyl sulfoxide (DMSO), formic acid, n-butanol, isopropyl alcohol (IPA), ethanol, water or their mixtures thereof.

15. The coating formulation according to any one of claims 8 to 14, further comprising metal alkoxides or metal nanoparticles.

16. The coating formulation according to claim 15, wherein the metal alkoxides are aluminum alkoxide, zinc alkoxide or zirconium alkoxide.

17. The coating formulation according to claim 15 or 16, wherein the metal nanoparticles are zinc, aluminum, iron, cobalt, nickel, copper, manganese, chromium, vanadium, germanium, tin; or their mixtures and/or alloys thereof.

18. The coating formulation according to any one of claims 8 to 17, further comprising fluorinated silane surfactants for imparting hydrophobicity.

19. A composite surface coating comprising the antimicrobial agent according to any one claims 1 to 7, whereby said coating is provided with terminal silicate groups, dispersed within a sol-gel matrix.

20. The composite surface coating according to claim 19, wherein the thickness of the composite surface coating is in the range of 50 nm to 1 mm.

21. A method of preparing antimicrobial agent according to any one of claims 1 to 7, comprising the steps of reacting a polymer with a halogenated benzyl alcohol or a halogenated alkyl alcohol in the presence of an organic solvent to impart terminal hydroxyl tails to the polymer, wherein the polymer comprises repeating units according to formula (I):

22. The method according to claim 21, wherein the halogenated alkyl alcohol has the formula X-(CH2)_n-OH, where n is an integer between 1 to 16 and X is chlorine, bromine or fluorine.

23. The method according to claim 21 or 22, wherein the halogenated alkyl alcohol is selected from the group consisting of 2-chloroethanol, 3 -chloro-1 -propanol, 2-chloro-l- propanol, 4-chloro-l -butanol, 5-chloro-l-pentanol, 6-chloro-l-hexanol, 4-chloro-l-hexanol, 7- chloro-l-heptanol, 8-chloro-l-octanol, 9-chloro-l-nonanol, 10-chloro-l-decanol, 11-chloro-l- undecanol, 12-chloro-l-dodecanol, 16-chloro-l-hexadecanol, 2-bromoethanol, 3-bromo-l- propanol, 2-bromo-l -propanol, 4-bromo-l -butanol, 5-bromo-l-pentanol, 6-bromo-l-hexanol, 4-bromo-l-hexanol, 7-bromo-l-heptanol, 8-bromo-l-octanol, 9-bromo-l-nonanol, 10-bromo- 1-decanol, 11-bromo-l-undecanol, 12-bromo-l-dodecanol, 16-bromo-l-hexadecanol and their mixtures thereof.

24. The method according to claim 21, wherein the polymer of the antimicrobial agent and the halogenated benzyl alcohol are mixed with a molar ratio from 1: 2 to 1:5.

25. The method according to any one of claims 21 to 24, wherein the reacting step is conducted at a temperature between about 65 °C and about 100 °C. 26. The method according to any one of claims 21 to 25, wherein the reacting step is conducted for about 1 hour to about 24 hours.

27. The method according to any one of claims 21 to 26, wherein the organic solvent is ethanol, tetrahydrofuran (THF), acetonitrile, or N-N-dimethylformamide (DMF).

28. A method of preparing the composite surface coating according to claim 19 or 20, comprising the steps of reacting the antimicrobial agent according to any one of claims 1 to 7 with at least one sol-gel precursor in the presence of a solvent to disperse the antimicrobial agent within a polymer matrix to form a sol-gel coating formulation, applying the coating formulation to a substrate and drying the substrate.

29. The method according to claim 28, wherein the substrate is plastic, stainless steel, glass or ceramics. 30. The method according to claim 28 or 29, wherein the plastic is polycarbonate or polypropylene.

31. Use of the composite surface coating according to claim 19 or 20 for antimicrobial applications.