GRAFTABLE BIOCIDAL LINKERS AND POLYMERS AND USES THEREOF

Abstract

Ready-to-graft compositions comprising polymers and Surrounding Tissue compounds and at least one grafting enhancer and/or grafting adjuvant, surfaces grafted to same, and methods of making and using the same for controlling the growth of at least one bacteria, fungi, protozoa, or virus are disclosed.

Description

FIELD

The disclosure relates generally to novel compositions comprising graftable linkers, such as catechol and dipodal silane linkers, and at least one grafting enhancer and/or grafting adjuvant, and polymers having both biocidal and biocompatibility properties, methods of preparation of same, and methods of grafting same on surfaces to prevent and reduce the colonization and proliferation of germs (e.g. bacteria, viruses, and fungi) on surfaces and surfaces.

BACKGROUND

Biocidal polymers are becoming increasingly important in order to contain and control the spread of infectious pathogens in a variety of health and industrial applications. To this end, biocidal polymers have been developed for use in solution form as well as to incorporate biocidal activity onto materials via coatings.

It would be highly desirable to have a solution of a biocidal polymer having both biocidal and biocompatibility properties for a prolonged storage period. It is, therefore, advisable to have a ready-to-use biocidal product which prevents fast reticulation in volume and thereby prolonging storage period.

SUMMARY

In one aspect, the disclosure provides a composition comprising a polymer comprising at least one moiety of formula (XVIIa) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

In some embodiments, the polymer includes at least one moiety of formula (XVIIa):

wherein in formula (XVIIa):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer includes at least one moiety of formula (XVIIb) or formula (XVIIe):

wherein in formula (XVIIb):G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10;

wherein in formula (XVIIe):

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer further includes at least one moiety of formula (III):

wherein in formula (III):

r is an integer from 3 to 20.

In some embodiments, the polymer includes at least one moiety of formula (XVIIc):

wherein in formula (XVIIc):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

r is an integer from 3 to 11;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer further includes at least one moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl.

In some embodiments, the polymer includes at least one moiety of formula (XVIIg):

wherein in formula (XVIIg):

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer further includes at least one moiety of formula (XVIIh):

In some embodiments, the polymer includes at least one moiety of formula (XVIIf):

wherein in formula (XVIIf):

each R² is independently optionally substituted alkyl. In some embodiments, each R² is independently a C₁-C₄ alkyl.

In some embodiments, the polymer includes least one moiety of formula (XVIId):

In one aspect, the disclosure includes at least one moiety of formula (XXI):

wherein in formula (XXI):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer includes at least one moiety of formula (XXIa) or formula (XXII):

wherein in formula (XXIa):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10;

wherein in formula (XXII):

each R² is independently optionally substituted alkyl;

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, the polymer includes at least one moiety of formula (XXIb):

wherein r is an integer from 3 to 20.

In some embodiments, the polymer includes at least one moiety of formula (XXId):

wherein in formula (XXId):

r is an integer from 3 to 11

In some embodiments, the polymer includes at least one moiety of formula (XXIIa):

wherein in formula (XXII):

each R² is independently optionally substituted alkyl.

In some embodiments, the polymer includes further at least one moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl.

In some embodiments, the polymer includes at least one moiety of formula (XXIIc):

In one aspect, the invention includes a polymer comprising at least one moiety of formula (II):

wherein in formula (XVIIf):

each R² is independently optionally substituted alkyl. In some embodiments, each R² is independently a C₁-C₄ alkyl.

In one aspect, the disclosure includes at least one moiety of formula (XVIIf):

In some embodiments, the polymer includes at least one moiety of formula (III):

wherein r is an integer from 3 to 20.

In some embodiments, the polymer includes at least one moiety of formula (IV):

wherein in formula (IV):

r is an integer from 3 to 11.

In one aspect, the disclosure provides composition comprising a polymer comprising at least one moiety of formula (V) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (V):

each R² is independently optionally substituted alkyl.

In some embodiments, the polymer comprises at least one moiety of formula (VI):

In some embodiments, the polymer further comprises a moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl.

In some embodiments, the polymer further includes at least one moiety of formula (VIII):

wherein in formula (VIII):

each R⁶ is independently optionally substituted alkyl.

In some embodiments, the polymer includes polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide), poly(diallyldimethylammonium), or a C₃-C₂₂ alkyne.

In one aspect, the disclosure provides a composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXa), formula (IXb), or formula (IXh) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (IXa), formula (IXb), and formula (IXh):

each R² is independently optionally substituted alkyl.

In some embodiments, the PEI polymer comprises one or more of the following moieties:

In some embodiments, R² is selected from methyl and hexyl. In some embodiments, PEI polymer comprises one or more of the following moieties, and one R² is methyl and one R² is hexyl:

In some embodiments, the PEI polymer includes at least one moiety of formula (IXc) or (IXd):

In some embodiments, the PEI polymer includes at least one moiety of formula (IXe), or any substructure thereof:

wherein in formula (IXe):

each R⁴ is independently optionally substituted alkyl; and

each R⁵ is independently optionally substituted alkyl or a moiety of formula (Ia):

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In one aspect, the disclosure includes a composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXf), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (IXf):

each R⁵ is independently C₁₀ alkyl

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In one aspect, the disclosure provides a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXg), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent thereof:

wherein in formula (IXg):

each R⁵ is independently C₆ alkyl or

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In one aspect, the disclosure provides a composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa), and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (XIa):

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10.

In some embodiments, the PEI polymer comprises at least one of the following moieties

wherein each R² is independently optionally substituted alkyl. In some embodiments, each R³ is hexyl. In some embodiments, R² is methyl. In some embodiments, v is 3. In some embodiments, the PEI polymer comprises one or more of the following moiety, wherein one R² is hexyl and one R² is methyl:

In some embodiments, the disclosure provides a composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIb), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (XIb):

each R⁴ is independently optionally substituted alkyl; and

each R⁵ is independently optionally substituted alkyl or a moiety of formula (XIa):

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10,

with the proviso that at least one R⁵ is a moiety of formula (XIa):

In one aspect, the disclosure provides a composition comprising polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIc), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (XIc):

each R⁵ is independently C₆ alkyl or

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10,

with the proviso that at least one R⁵ is

In some embodiments, each moiety of formula (XIa)

In some embodiments, Z is selected from

wherein R is selected from

wherein is an integer from 1 to 5.

In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is a cross-linking reagent. In some embodiments, the cross-linking reagent is selected from tetramethylorthosilicate, trimethylmethoxyorthosilicate, trimethylethoxyorthosilicate, dimethyldimethoxyorthosilicate, dimethyldiethoxyorthosilicate, methyltrimethoxyorthosilicate, methyltriethoxyorthosilicate, tetramethoxyorthosilicate, tetraethoxyorthosilicate, methyldimethoxyorthosilicate, methyldiethoxyorthosilicate, dimethylethoxyorthosilicate, dimethylvinylmethoxyorthosilicate, dimethylvinylethoxyorthosilicate, tetraethylorthosilicate, methylvinyldimethoxyorthosilicate, methylvinyldiethoxyorthosilicate, diphenyldimethoxyorthosilicate, diphenyldiethoxyorthosilicate, phenyltrimethoxyorthosilicate, phenyltriethoxyorthosilicate, octadecyltrimethoxyorthosilicate and octadecyltriethoxyorthosilicate, 1,3-Disiloxanediol, 1,1,3,3-tetramethyl, 1,1,3,3-tetramethyldisiloxane-1,3-diol, 1,1,3,3-tetramethoxy-1,3-dimethyldisiloxane, tetraethoxy-1,3-dimethyldisiloxane, and 1,5-diethoxyhexamethyltrisiloxane

In one aspect, the disclosure provides a surface having a polymer of the disclosure or a compound of the disclosure grafted thereon. In some embodiments, the surface comprises a material selected from metals such as titanium and titanium alloys, iron, and steel; metal oxides; ceramics; polymers such as polyethylene (low and high reticulation for use in biomedical implants, after prior plasma activation), teflon (after prior plasma activation), polyethylene terephthalate (after prior plasma activation), and polypropylene (low and high density, after prior plasma activation), silicones, rubbers, latex, plastics, polyanhydrides, polyesters, polyorthoesters, polyamides, polyacrylonitrile, polyurethanes, polyethylene, polytetrafluoroethylene, polyethylenetetraphthalate and polyphazenes; paper; leather; textiles or textile materials such as cotton, jute, linen, hemp, wool, animals hair and silk, synthetic fabrics such as nylon and polyester; textile material comprising fibers comprising fiber material such as acrylic polymers, acrylate polymers, aramid polymers, cellulosic materials, cotton, nylon, polyolefins, polyester, polyamide, polypropylene, rayon, wool, spandex, silk, and viscose; silicon; wood; glass; cellulosic compounds; and gels and fluids not normally found within the human body.

In one aspect, the disclosure provides a method of controlling the growth of at least one bacteria, fungi, protozoa, or virus, the method comprising grafting a polymer of the disclosure or a compound of the disclosure onto a surface. In some embodiments, the bacteria is a gram-positive bacteria selected from M tuberculosis (including multi drug resistant TB and extensively drug resistant TB), M bovis, M typhimurium, M bovis strain BCG, BCG substrains, M avium, M intracellulare, M africanum, M kansasii, M marinum, M ulcerans, M avium subspecies paratuberculosis, Staphylococcus aureus (including Methicillin-resistant Staphylococcus aureus (MIRSA)), Staphylococcus epidermidis, Staphylococcus equi, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Listeria ivanovii, Bacillus anthraces, B. subtilis, Nocardia asteroides, and other Nocardia species, Streptococcus viridans group, Peptococcus species, Peptostreptococcus species, Actinomyces israelii and other Actinomyces species, Propionibacterium acnes, Clostridium tetani, Clostridium perfringens, Clostridium botulinum, other Clostridium species, and Enterococcus species. In some embodiments, the bacteria is a gram-negative bacteria selected from Pseudomonas aeruginosa, other Pseudomonas species, Campylobacter species, Vibrio cholerae, Ehrlichia species, Actinobacillus pleuropneumoniae, Pasteurella haemolytica, Pasteurella multocida, other Pasteurella species, Legionella pneumophila, other Legionella species, Salmonella typhi, other Salmonella species, Shigella species, Brucella abortus, other Brucella species, Chlamydi trachomatis, Chlamydia psittaci, Coxiella burnetti, Escherichia coli, Neiserria meningitidis, Neiserria gonorrhea, Haemophilus influenzae, Haemophilus ducreyi, other Hemophilus species, Yersinia pestis, Yersinia enterolitica, other Yersinia species, Escherichia coli, Escherichia hirae, and other Escherichia species, as well as other Enterobacteriacae, Burkholderia cepacia, Burkholderia pseudomallei, Francisella tularensis, Bacteroides fragilis, Fusobascterium nucleatum, Provetella species, Cowdria ruminantium, Klebsiella species, and Proteus species. In some embodiments, the virus is selected from influenza, Middle East respiratory syndrome-related coronavirus (MERS-CoV), rhinovirus, polio, measles, Ebola, Coxsackie, West Nile, yellow fever, Dengue fever, lassa, lymphocytic choriomeningitis, Junin, Machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), parainfluenza, Tacaribe, and Pichinde viruses.

In one aspect, the disclosure provides a coating comprising metal oxide nanoparticles and one or more polymers of the disclosure and/or one or more compounds of the disclosure. In some embodiments, a plurality of the metal oxide nanoparticles are substantially in contact with a surface. In some embodiments, the one or more polymers are grafted onto the surface of one or more of metal oxide nanoparticles. In some embodiments, the metal oxide nanoparticles comprise titanium oxide nanoparticles.

In one aspect, the disclosure provies a solution comprising an alcohol and at least one composition of the disclosure. In some embodiments, the alcohol is selected from ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the solution is stable for up to 1 day, up to 2 days, up to 3 days, up to 4 days, up to 5 days, up to 6 days, up to 7 days, up to 2 weeks, up to 3 weeks, up to 1 month, up to 2 months, up to 3 months, up to 4 months, up to 5 months, up to 6 months, up to 7 months, up to 8 months, up to 9 months, up to 10 months, up to 11 months, up to 1 year, or up to 2 years after preparation.

In one aspect, the disclosure provides a method of preparing the composition of the disclosure, the method comprising mixing at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, with at least one polymer and/or at least one compound of the disclosure.

In one aspect, the disclosure provides a method of preparing the solution of the disclosure, the method comprising adding at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, to a solution comprising an alcohol and at least one polymer and/or at least one compound of the disclosure.

In some embodiments, the composition, solution, and/or the method of the disclosure includes the polymer and/or the compound of the disclosure in an amount of about 99.9% to about 50% (v/v), about 99.9% to about 60% (v/v), about 99.9% to about 70% (v/v), or about 99.5% to about 75% (v/v), and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% to about 50% (v/v), about 0.1% to about 40% (v/v), about 0.1% to about 30% (v/v), or about 0.5% to about 25% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant.

In some embodiments, the composition, solution, or the method of the disclosure includes the polymer and/or the compound of the disclosure in an amount of about 99.9% (v/v), 99.8% (v/v), 99.7% (v/v), 99.6% (v/v), 99.5% (v/v), 99.4% (v/v), 99.3% (v/v), 99.2% (v/v), 99.1% (v/v), 99% (v/v), 98% (v/v), 97% (v/v), 96% (v/v), 95% (v/v), 94% (v/v), 93% (v/v), 92% (v/v), 91% (v/v), 90% (v/v), 85% (v/v), 80% (v/v), 75% (v/v), 70% (v/v), 65% (v/v), 60% (v/v), 55% (v/v), or 50% (v/v), and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% (v/v), 0.2% (v/v), 0.3% (v/v), 0.4% (v/v), 0.5% (v/v), 0.6% (v/v), 0.7% (v/v), 0.8% (v/v), 0.9% (v/v), 1% (v/v), 2% (v/v), 3% (v/v), 4% (v/v), 5% (v/v), 6% (v/v), 7% (v/v), 8% (v/v), 9% (v/v), 10% (v/v), 15% (v/v), 20% (v/v), 25% (v/v), 30% (v/v), 35% (v/v), 40% (v/v), 45% (v/v), or 50% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant. In some embodiments, the composition, solution, or the method of the disclosure includes the polymer and/or the compound of the disclosure and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, at a ratio between about 400:1 and about 1:1, between about 300:1 and about 2:1, or between about 200:1 and about 3:1.

In some embodiments, the composition, solution, or the method of the disclosure includes the polymer and/or the compound of the disclosure and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, at a ratio of about 400:1, about 350:1, about 300:1, about 250:1, about 200:1, about 150:1, about 100:1, about 50:1, about 40:1, about 30:1, about 20:1, about 10:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1.

In one aspect, the disclosure provides a method of preparing a conjugated biomolecule, the method comprising grafting a catechol moiety of formula (Ib) on to a surface, and reacting the compound of formula (Ib′) with a biomolecule of formula (XLb):

wherein in formula (Ib′):

X comprises a reactive group and/or a leaving group;

wherein in formula (XLb):

Z′ comprises a reactive group and/or a leaving group; and

B is a biomolecule.

In some embodiments, X comprises a reactive group and/or a leaving group selected from halo, —SH, —N₃,

wherein R is a linker. In some embodiments, R is selected from

wherein is an integer from 1 to 5,

wherein is an integer from 1 to 5, and

wherein is an integer from 1 to 5, optionally wherein R is

In some embodiments, Z′ comprises a reactive group and/or a leaving group selected selected from halo, —SH, —N₃,

In some aspects, the disclosure provides a solution comprising an alcohol and a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa), and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

wherein in formula (XIa):

each R³ is independently optionally substituted alkoxy, optionally methoxy; and

v is an integer from 3 to 10;

wherein the solution comprises at least one moiety of formula (XIa) in an amount of about 70% to about 80%, optionally about 75% by weight based on the weight of the solution, and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 20% to about 30% (v/v), optionally about 25% (v/v) of the solution. In some embodiments, the PEI polymer comprises one or more of the following moiety, wherein one R² is hexyl and one R² is methyl:

In some embodiments, each R³ is methoxy and v is 3. In some embodiments, the grafting enhancer and/or grafting adjuvant is a cross-linking reagent is or comprises tetraethoxyorthosilicate (tetraethoxysilane, TEOS). In some embodiments, the molecular weight of the PEI polymer is of a range of about 700 kDa to about 800 kDa, optionally about 750 kDa.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates a comparison between control and ODMcat-treated filter paper after sonicating and drying. The orange appearance of ODMcat-treated filter paper is due to the high number of counter ion of the fluorescein dye bound to the quaternary amino groups of the ODMcat moiety, which is covalently attached to the cotton.

FIG. 2 illustrates a comparison between control and ODMcat-treated cotton after vortexing, sonication and drying. The orange appearance of ODMcat-treated cotton is due to the extremely high number of counter ion of the fluorescein dye bound to the quaternary amino groups of the ODMcat moiety, which is covalently attached to the cotton.

FIG. 3 illustrates a comparison between control and C2-treated cotton after vortexing.

FIG. 4 illustrates a comparison between control and C2-treated cotton after vortexing, sonication and drying. The orange appearance of C2-treated cotton is due to the extremely high number of counter ion of the fluorescein dye bound to the quaternary amino groups of the C2 moiety, which is covalently attached to the cotton.

FIG. 5 illustrates a comparison between control and C2-treated filter paper after fluorescein test. The orange appearance of C2-treated filter paper is due to the extremely high number of fluorescein dye molecules bound to the quaternary amino groups of the C2 moiety, which is covalently attached to the cotton.

FIG. 6 illustrates the structure of a monomer of poly(vinylbenzyl chloride).

FIG. 7 illustrates the structure of a monomer of polyethylenimine.

FIG. 8 illustrates the structure of a fully methylated monomer of PEI.

FIG. 9 illustrates an exemplary synthesis to produce bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium compounds. In some embodiments, bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium compounds are both hydrophobic and hydrophilic.

FIG. 10 illustrates an exemplary synthesis of bis(3-trimethoxysilylpropyl)-N,N-methylalkylammonium bromide. In some embodiments, bis(3-trimethoxysilylpropyl)-N,N-methylalkylammonium compounds exhibit antimicrobial properties.

FIG. 11A illustrates an exemplary synthesis of bis(3-trimethoxysilylpropyl)dialkylammonium halide from bis(3-methoxysilylpropyl)amine and alkyl bromide (bromide may also be substituted for chloride or iodide). FIG. 11B illustrates an exemplary synthesis of bis(3-trimethoxysilylpropyl)difluoroalkylammonium bromide from bis(3-methoxysilylpropyl)amine and a perfluorinated alkyl bromide (bromide may also be substituted for chloride or iodide).

FIG. 12A illustrates an exemplary synthesis to prepare a polyvinylpyridine polymer comprising a monomer comprising a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety linked to the PVP polymer by a —CH₂-Ph-CH₂— linking group, and a monomer comprising a C₄-C₁₂ alkyl moiety (r=3-11), by reacting α,α′-Dibromo-p-xylene with bis(3-trimethyoxysilylpropyl)-N-methyamine, followed by treatment with polyvinylpyridine and then treatment with a C₄-C₂₂ alkyl halide, such as a C₄-C₂₂ alkyl bromide. x represents the molar ratio of the monomer comprising a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety, and (1-x) represents the molar ratio of the monomer comprising the alkylated quaternary pyridine moiety. FIG. 12B illustrates an exemplary synthesis to prepare a polymer comprising a monomer comprising a tertiary amine linked to a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety by a —C(CO)CH₂— linking group. x represents the molar ratio of the monomer comprising a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety, and (1-x) represents the molar ratio of the monomer comprising the quaternary trialkylamine moiety. FIG. 12C illustrates an exemplary synthesis to prepare a polyvinylpyridine polymer comprising a monomer comprising a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety linked to the PVP polymer by a —C(O)CH₂-linking group, and a monomer comprising a C₄-C₁₂ alkyl moiety (r=3-11), by reacting α,α′-Dibromo-p-xylene with bis(3-trimethoxysilylpropyl)-N-methylamine, followed by treatment with polyvinylpyridine and then treatment with a C₄-C₂₂ alkyl halide, such as a C₄-C₂₂ alkyl bromide. x represents the molar ratio of the monomer comprising a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety, and (1-x) represents the molar ratio of the monomer comprising the alkylated quaternary pyridine moiety. In a non-limiting embodiment, x is about 10, and 1-x is about 90.

FIG. 13 illustrates an exemplary synthesis of a polymer comprising a monomer comprising quaternary bis(3-trimethoxysilylpropyl)-N-methylalkylammonium moiety and a monomer comprising a quaternary dialkyl amine, such as (CH₃)₂N[(CH₂)_rCH₃], wherein r is 3-11.

FIG. 14 illustrates an IR spectrum of Octadecyl(4-catecholacetyl)dimethylammonium chloride. The bands at 2918 cm⁻¹ and 2852 cm⁻¹ correspond to the C—H stretching and show the successful introduction of the alkyl chain. 1684 cm⁻¹ bands are identical in the two spectra. They are due to the carbonyl aromatic stretching. The spectrum includes the comparative spectrum of 4-chloroacetylcatechol.

FIG. 15 illustrates an IR spectrum catecholacetyl-cobutyl PVP spectrum (blue line). The figure includes the comparative spectrum of 4-chloroacetylcatechol (pink line).

FIG. 16 illustrates an IR spectrum of poly(vinylbenzyl chloride) partially quaternized with bis(N-methyl)3propyltrimethoxysilane groups and N,N-dimethylbutyl groups compared to the commercial poly(vinylbenzyl chloride) (55 kDa). The solvent is still visible on the 3378 cm⁻¹ band. The three bands corresponding to v CH2, CH3 are the alkyl chains. Dotted line bands represent the v CH2 of the benzyl groups in polyvinylbenzylchloride. The CH2, CH3 bands of the alkyl chains show the appropriate quaternization of the polymer.

FIG. 17 illustrates an IR spectrum of bis(3-trimethoxysilyl)propyl-N,N-dioctadecyl ammonium bromide. The three bands at 2970 cm⁻¹, 2921 cm⁻¹ and 2853 cm⁻¹ are due to the CH2, CH3 stretching. The bands at 1034 cm⁻¹ and 888 cm⁻¹ are the fingerprint of the methoxysilane moiety.

FIG. 18 illustrates an IR spectrum of the catecholacetyl-cobutyl PVP co-polymer with non-quaternized PVP in the background.

FIG. 19 illustrates an IR spectrum of the catecholacetyl-cobutyl PVP co-polymer. The bands at 2935 cm⁻¹ and 2871 cm⁻¹ show the C—H stretching in the butyl chain. The spectrum shows the intense bands due to the C—N⁺ stretching in the polymer (1634 cm⁻¹). The band at 1680 cm⁻¹ is due to the aromatic carbonyl of the catechol which corresponds to the shoulder at the same frequency in the catechol moiety incorporated in the polymer.

FIG. 20 illustrates an IR spectrum of the catecholacetyl-codecyl PVP co-polymer with non-quaternized PVP in the background. The three bands at 2954 cm⁻¹, 2923 cm⁻¹, and 2853 cm⁻¹ are due to the CH2, CH3 stretching. The 1639 cm⁻¹ band represents the C—N⁺ stretching. The 1678 cm⁻¹ band represents the aromatic nu C═O of the catechol moiety.

FIG. 21 illustrates an IR spectrum of the poly(vinylbenzyl chloride) co-polymer partially quaternized with bis(N-methyl)3propyltrimethoxysilane groups and N,N-dimethylbutyl groups. The solvent is still visible on the 3373 cm⁻¹ band. The three bands corresponding to v CH2, CH3 are the alkyl chains. The band CH2, CH3 of the alkyl chains show the appropriate quaternization of the polymer.

FIG. 22 illustrates an IR spectrum of fully methylated quaternized PEI random copolymer partially grafted with acetylcatechol group and decyl group in ratio 1/9. The v CH aromatic band is located at 3009 cm⁻¹. The three bands CH3, CH2 represent the alkyl chains. There is a slight shoulder at 1674 cm⁻¹ due to the aromatic carbonyl stretching. The 1633 cm⁻¹ band is due to the C—N⁺ stretching.

FIG. 23 illustrates IR spectra of methylated hyperbranched PEI (750 kDa) and commercial PEI (750 kDa). The disappearance of the 3277 cm⁻¹ band in the methylated PEI random copolymer proves that the methylation was near complete compared with polyethylenimine.

FIG. 24 illustrates an IR spectrum of a dipodal quaternized PVP, which is a partially quaternized PVP random copolymer with a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety and a butyl moiety in 1/9 ratio.

FIG. 25 illustrates an IR spectrum of bis(3-trimethoxysilypropyl)-N-bromoacetylamine.

FIG. 26 illustrates an IR spectrum of dipodal quaternized PVP, which is a partially quaternized PVP random copolymer with a quaternary bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl moiety and a butyl moiety in 1/9 ratio compared to the intermediate product bis(3-trimethoxysilypropyl)-N-bromoacetylamine. The 1639 cm⁻¹ band shows the quaternization of PVP. The bands at 1063 cm⁻¹ and 903 cm⁻¹, and 913 cm⁻¹ correspond to the methoxysilane moiety that are both present in the bis(3-trimethoxysilypropyl)-N-bromoacetylamine compound and the dipodal quaternized PVP.

FIG. 27 illustrates an IR spectrum of poly(vinylbenzyl chloride) partially quaternized with bis(N-methyl)3propyltrimethoxysilane groups and N,N-dimethylbutyl groups compared to the commercial poly(vinylbenzyl chloride) (55 kDa). The solvent is still visible on the 3378 cm¹ band. The three bands corresponding to v CH2, CH3 are the alkyl chains. Dotted line bands represent the v CH2 of the benzyl groups in polyvinylbenzylchloride. The CH2, CH3 bands of the alkyl chains show the appropriate quaternization of the polymer.

FIG. 28A illustrates an exemplary scheme for the attachment of a biomolecule (e.g. protein, enzyme, peptide) containing a thiolated amino acid (e.g. R—SH) to a catechol moiety of the disclosure through azide-alkyne cycloaddition in two steps. In step A, the alkyne group is introduced in the biomolecule through a Michael addition. In step B, the biomolecule is attached to the catechol moiety through triazole formation between the alkyne and the azide groups. In step C, the catchol moiety can be grafted onto surfaces. FIG. 28B illustrates illustrates an exemplary scheme for the attachment of a biomolecule (e.g. protein, enzyme, peptide) containing a thiolated amino acid (e.g. R—SH) to a catechol moiety of the disclosure grafted to a surface through azide-alkyne cycloaddition in two steps.

FIG. 29 illustrates an exemplary scheme for the attachment of a biomolecule (e.g. protein, enzyme, peptide) containing a thiolated amino acid (e.g. R—SH) to a catechol moiety of the disclosure through a Michael addition. In step A, the maleimide is introduced in the catechol moiety. In step B, the biomolecule is attached to the maleimide through a Michael addition.

FIG. 30 illustrates an exemplary scheme for the attachment of a biomolecule (e.g. protein, enzyme, peptide) containing a thiolated amino acid (e.g. R—SH) to a catechol moiety through nucleophilic substitution. The thiol group of the biomolecule displaces the iodide group of the catechol moiety under buffered conditions to provide the conjugated product. A non-limiting example of buffered conditions include maintaining reaction nconditions at a pH of about 8.3 using a borate buffer.

FIG. 31 illustrates an exemplary scheme for the attachment of a biomolecule (e.g. protein, enzyme, peptide) containing a thiolated amino acid (e.g. R—SH) to a catechol moiety comprising two maleimide moieties, wherein the maleimide moieties are conjugated to each other by way of a linker R. The thiol group of the catechol moiety is first conjugated to one of the maleimide moieties, and then the biomolecule is conjugated to the second maleimie moiety by way of a thiol group. Non-limiting examples of the linker R are shown.

FIG. 32 illustrates a non-limiting example of a method of preparing a biocidal coating of the disclosure.

FIG. 33 illustrates an IR spectrum of bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium bromide. The three bands at 2950 cm⁻¹, 2921 cm⁻¹ and 2851 cm-1 are due to the CH2, CH3 stretching. The bands at 1040 cm⁻¹ and 886 cm⁻¹ are the fingerprint of the methoxysilane moiety.

FIG. 34 illustrates an IR spectrum of fully methylated quaternized PEI random copolymer partially grafted with propyltrimethoxysilane group and a hexyl group in ratio 1/9. The 1631 cm⁻¹ band represents the C—N⁺ stretching. The CH2, CH3 stretching bands are seen at 2956 cm⁻¹, 2927 cm⁻¹, and 2859 cm⁻¹.

FIG. 35 illustrates a comparison between control and L-cysteine-grafted filter paper using 4-iodoacetylcatechol as a linker after 1% aqueous ninhydrin treatment. The treated filter paper appears purple, demonstrating the successful grafting of L-cysteine.

FIG. 36 illustrates a comparison between control and L-cysteine-grafted glass slides using 4-iodoacetylcatechol as a linker after 1% aqueous ninhydrin treatment. The treated glass slides displays multiple blue/purple spots, demonstrating the successful grafting of L-cysteine.

FIG. 37 illustrates a comparison between control filter paper and treated filter paper with quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP. The orange appearance of the filter paper treated with bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP is due to the high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The polymer is covalently grafted to the filter paper (remained on the filter paper despite sonication).

FIG. 38 illustrates a comparison between control filter paper and treated filter paper with poly(vinylbenzyl chloride) partially quaternized with bis(N-methyl)3-propyltrimethoxysilane groups and N,N-dimethylbutyl groups. The orange appearance of the filter paper treated with poly(vinylbenzyl chloride) partially quaternized with bis(N-methyl)3-propyltrimethoxysilane groups and N,N-dimethylbutyl groups is due to the high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The polymer is covalently grafted to the filter paper (remained on the filter paper despite sonication).

FIG. 39 illustrates a comparison between control filter paper and treated filter paper with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI (from PEI at 750 kDa). The orange appearance of the filter paper treated with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI is due to the high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The polymer is covalently grafted to the filter paper (remained on the filter paper despite sonication).

FIG. 40 illustrates a comparison between control filter paper and treated filter paper with 3-trimethoxypropylsilyl-codecyl-PEI (from PEI at 25 kDa). The orange appearance of the filter paper treated with 3-trimethoxypropylsilyl-codecyl-PEI is due to the relatively high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The polymer is covalently grafted to the filter paper (remained on the filter paper despite sonication).

FIG. 41 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilypropyl)-N-bromoacetylamine. The orange appearance of the filter paper treated with bis(3-trimethoxysilypropyl)-N-bromoacetylamine is due to the high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The compound is covalently grafted to the filter paper (remained on the filter paper despite sonication).

FIG. 42 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide. The orange appearance of the filter paper treated with bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide is due to the relatively high number of fluorescein dye molecules bound to the quaternary amino groups of the quaternary ammonium compounds. The monomer is covalently attached to the filter paper (remained on the filter paper despite sonication). The orange color sometimes appears slightly more intense for monomers than polymers with filter paper due to the fact that fluorescein penetrates deeper into the paper when only monomers are grafted. This is not related to the charge density.

FIG. 43 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilylpropyl)-N,N-methylalkylammonium bromide. The orange appearance of the filter paper treated with bis(3-trimethoxysilylpropyl)-N,N-methylalkylammonium bromide is due to the relatively high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The monomer is covalently attached to the filter paper (remained on the filter paper despite sonication). The orange color sometimes appears slightly more intense for monomers than polymers with filter paper due to the fact that fluorescein penetrates deeper into the paper when only monomers are grafted. This is not related to the charge density.

FIG. 44 illustrates a comparison between control filter paper and treated filter paper with bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium. The orange appearance of the filter paper treated with bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium is due to the relatively high number of fluorescein dye molecules bound to the quaternary ammonium compounds. The monomer is covalently attached to the filter paper (remained on the filter paper despite sonication). The orange color sometimes appears slightly more intense for monomers than polymers with filter paper due to the fact that fluorescein penetrates deeper into the paper when only monomers are grafted. This is not related to the charge density.

FIG. 45 illustrates the relationship between the number of autoclaving cycles and sample cationic charge densities of stainless steel samples grafted with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI/TEOS. While the charge density initially varied between samples and significantly decreased between the first and 5th cycles, it was found that after 5 cycles, the charge density remained constant (6th through 9th), above the density threshold for biocidal activity (10¹⁵ charges/cm²).

FIG. 46 displays Lisogeny Broth (LB) agar plates and is clearly indicative of a high bactericidal activity (>4 log reduction) that persisted despite prior sterilization by gamma-irradiation of 3-trimethoxypropylsilyl-cohexyl-methylatedPEI-grafted titanium-alloy samples (no colonies visualized on plates corresponding to either 70% ethanol-sterilized samples or gamma-irradiated samples). The first two columns from the left correspond to plated dilutions of bacterial suspensions in contact with 70% ethanol-sterilized control titanium alloy plates. The third and fourth columns from the left correspond to plated dilutions of bacterial suspensions in contact with gamma-irradiated control titanium alloy plates. The first column on the right corresponds to plated dilutions of bacterial suspensions in contact with 70% ethanol-sterilized treated titanium plates. The second and third column from the right correspond to plated dilutions of bacterial suspensions in contact with gamma-irradiated treated titanium plates.

FIG. 47 illustrates the turbidity difference between BHI solutions inoculated and incubated at 37° C. with either control or 3-trimethoxypropylsilyl-cohexyl-methylatedPEI-grafted filter paper that had been in prior contact (1 hour) with a 10 μL Staphylococcus epidermidis bacterial suspension at 10⁶ CFU/mL. High turbidity is seen in the BHI solutions containing control filter paper (left two) while the BHI solutions containing treated filter paper appear perfectly clear (right two).

FIG. 48 illustrates a scheme showing a non-limiting example of deposition, covalent grafting, and cross-linking of a polymer of the disclosure (methylated PEI-based random copolymer quaternized with bromohexane (3-trimethoxypropylsilyl-cohexyl-methylatedPEI)) on hydroxylated or activated surfaces.

FIG. 49 illustrates a scheme showing a non-limiting example of the preparation of a grafted biomolecule. This non-limiting example shows click-chemistry involving the covalent grafting of 4-azidocatechol on a substrate, followed by the introduction of a propargyl-bearing biomolecule.

FIG. 50 illustrates body weight measurement (expressed as % body weight, mean±SD) in DBG21-treated and untreated mice up to 11 days post-implantation.

FIG. 51 illustrates clinical scores (expressed as % body weight, mean±SD) in DBG21-treated and untreated mice up to 11 days post-implantation.

FIGS. 52A-52K illustrate a biochemical assessment (median is presented) from animals receiving untreated or DBG21-treated implants at dl1 post-implantation. A: Urea, B: Creatinine, C: Total Protein, D: Serum albumin, E: Alkaline Phosphatase, F: Transaminases S.G.P.T, G: Glutamate dehydrogenase, H: Sodium, I: Potassium, J: Chlore, K: Glycaemia.

FIG. 53 is a representative picture of the control implant cavity with different magnifications in the absence of infection (implant tolerance). Presence of an optically empty cavity (*) in the subcutaneous adipose-connective location, circumscribed by a light fibrous densification (arrow). Slight leukocytic densification in the loose connective tissue at the periphery of the polymorphic cavity, predominantly mononuclear (o). Pictures from sample DGB1 are representative for the samples DGB3 and DGB4.

FIG. 54 is a representative picture of the treated implant cavity with different magnifications in the absence of infection (implant tolerance). Absence of cavitary lesion in the subcutaneous connective tissue. Minimal leukocyte densification in loose, predominantly mononuclear connective tissue (o). Pictures from sample DGB7 are representative for the samples DGB6, DGB8, and DGB10.

FIG. 55 is a representative picture of the implant tolerance. The left panel shows samples with neutral titanium implants, and the right panel shows samples with treated titanium implants.

FIGS. 56A-56D illustrate the titanium implant effects on the adjacent tissues at D11 in the absence of infection: inflammation rate (FIG. 56A); fibrosis rate (FIG. 56B); angiogenesis (FIG. 56C); necrosis rate (FIG. 56D).

FIGS. 57A-57B illustrate the antibacterial efficacy of DBG21-treated titanium implants versus controls against MRSA (ATCC 43300) biofilm in a mouse model of implant-associated infection after 7 and 14 days of infection in surrounding tissues (FIG. 57A) and on implants (FIG. 57B).

FIGS. 58A-58H illustrate the effect of titanium implants+bacterial inoculum on the adjacent tissues at two timepoints (D7 and D14). FIGS. 58A-58D illustrate the results observed after 7 days of implantation. FIGS. 58E-58H illustrate the results after 14 days of implantation. (FIGS. 58A, 58E) inflammation rate; (FIGS. 58B, 58F) fibrosis rate; (FIGS. 58C, 58G) angiogenesis rate; (FIGS. 58D, 58H) necrosis rate.

FIGS. 59A-59H illustrate the evolution of the implant effect on adjacent tissues over time. FIGS. 59A-59D: results observed with neutral implants. FIGS. 59E-59H show results observed with treated implants. FIGS. 59A and 59E show inflammation rate over time. FIGS. 59B and 59F show fibrosis rate over time. FIGS. 59C and 59G show angiogenesis rate over time. FIGS. 59D and 59H show necrosis rate over time.

DETAILED DESCRIPTION

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entireties.

Definitions

The term “biocide”, as used herein, means a chemical compound, a chemical composition, a chemical formulation which can kill or render harmless a microorganism exemplified by bacterium, yeast, protozoa, and fungi.

The term “statistical copolymer” as used herein is defined as a copolymer that is made up of more than one monomer, and in which the different monomer units are randomly distributed in the polymeric chain.

As used herein, the terms “graft” and “grafting” refer to the attachment of moieties onto a surface by forming covalent linkages between functional groups on the surface and the moiety.

Unless otherwise stated, the chemical structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds where one or more hydrogen atoms is replaced by deuterium or tritium, or wherein one or more carbon atoms is replaced by ¹³C- or ¹⁴C-enriched carbons, are within the scope of this invention.

When ranges are used herein to describe, for example, physical or chemical properties such as molecular weight or chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. Use of the term “about” when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range may vary. The variation is typically from 0% to 15%, preferably from 0% to 10%, more preferably from 0% to 5% of the stated number or numerical range. The term “comprising” (and related terms such as “comprise” or “comprises” or “having” or “including”) includes those embodiments such as, for example, an embodiment of any composition of matter, method or process that “consist of” or “consist essentially of” the described features.

“Alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to ten carbon atoms (e.g., (C_1-10)alkyl or C_1-10 alkyl). Whenever it appears herein, a numerical range such as “1 to 10” refers to each integer in the given range—e.g., “1 to 10 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms, although the definition is also intended to cover the occurrence of the term “alkyl” where no numerical range is specifically designated. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl isobutyl, tertiary butyl, pentyl, isopentyl, neopentyl, hexyl, septyl, octyl, nonyl and decyl. The alkyl moiety may be attached to the rest of the molecule by a single bond, such as for example, methyl (Me), ethyl (Et), n-propyl (Pr), 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (t-butyl) and 3-methylhexyl. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of substituents which are independently heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂ where each R^a is independently hydrogen, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

“Alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to ten carbon atoms (i.e., (C_2-10)alkynyl or C_2-10 alkynyl). Whenever it appears herein, a numerical range such as “2 to 10” refers to each integer in the given range—e.g., “2 to 10 carbon atoms” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms. The alkynyl may be attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl and hexynyl. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

“Carboxyl” refers to a —(C=O)OH radical.

“Cyano” refers to a —CN radical.

The term “alkoxy” refers to the group —O-alkyl, including from 1 to 8 carbon atoms of a straight, branched, cyclic configuration and combinations thereof attached to the parent structure through an oxygen. Examples include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy and cyclohexyloxy. “Lower alkoxy” refers to alkoxy groups containing one to six carbons.

The term “substituted alkoxy” refers to alkoxy wherein the alkyl constituent is substituted (i.e., —O-(substituted alkyl)). Unless stated otherwise specifically in the specification, the alkyl moiety of an alkoxy group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

“Amino” or “amine” refers to a —N(R^a)₂ radical group, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl, unless stated otherwise specifically in the specification. When a —N(R^a)₂ group has two R^a substituents other than hydrogen, they can be combined with the nitrogen atom to form a 4-, 5-, 6- or 7-membered ring. For example, —N(R^a)₂ is intended to include, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl. Unless stated otherwise specifically in the specification, an amino group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

The term “substituted amino” also refers to N-oxides of the groups —NHR^a, and NR^aR^a each as described above. N-oxides can be prepared by treatment of the corresponding amino group with, for example, hydrogen peroxide or m-chloroperoxybenzoic acid.

“Amide” or “amido” refers to a chemical moiety with formula —C(O)N(R)₂ or —NHC(O)R, where R is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon), each of which moiety may itself be optionally substituted. The R₂ of —N(R)₂ of the amide may optionally be taken together with the nitrogen to which it is attached to form a 4-, 5-, 6- or 7-membered ring. Unless stated otherwise specifically in the specification, an amido group is optionally substituted independently by one or more of the substituents as described herein for alkyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl. An amide may be an amino acid or a peptide molecule attached to a compound disclosed herein, thereby forming a prodrug. The procedures and specific groups to make such amides are known to those of skill in the art and can readily be found in seminal sources such as Greene and Wuts, Protective Groups in Organic Synthesis, 3^rd Ed., John Wiley & Sons, New York, N.Y., 1999, which is incorporated herein by reference in its entirety.

“Ester” refers to a chemical radical of formula —COOR, where R is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon). The procedures and specific groups to make esters are known to those of skill in the art and can readily be found in seminal sources such as Greene and Wuts, Protective Groups in Organic Synthesis, 3^rd Ed., John Wiley & Sons, New York, N.Y., 1999, which is incorporated herein by reference in its entirety. Unless stated otherwise specifically in the specification, an ester group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

“Halo,” “halide,” or, alternatively, “halogen” is intended to mean fluoro, chloro, bromo or iodo. The terms “haloalkyl,” “haloalkenyl,” “haloalkynyl,” and “haloalkoxy” include alkyl, alkenyl, alkynyl and alkoxy structures that are substituted with one or more halo groups or with combinations thereof. For example, the terms “fluoroalkyl” and “fluoroalkoxy” include haloalkyl and haloalkoxy groups, respectively, in which the halo is fluorine.

“Heteroaryl” or “heteroaromatic” or “HetAr” or “Het” refers to a 5- to 18-membered aromatic radical (e.g., C₅-C₁₃ heteroaryl) that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur, and which may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system. Whenever it appears herein, a numerical range such as “5 to 18” refers to each integer in the given range—e.g., “5 to 18 ring atoms” means that the heteroaryl group may consist of 5 ring atoms, 6 ring atoms, etc., up to and including 18 ring atoms. Bivalent radicals derived from univalent heteroaryl radicals whose names end in “-yl” by removal of one hydrogen atom from the atom with the free valence are named by adding “-idene” to the name of the corresponding univalent radical—e.g., a pyridyl group with two points of attachment is a pyridylidene. A N-containing “heteroaromatic” or “heteroaryl” moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom. The polycyclic heteroaryl group may be fused or non-fused. The heteroatom(s) in the heteroaryl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl may be attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzofurazanyl, benzothiazolyl, benzothienyl(benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furazanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, thiapyranyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl moiety is optionally substituted by one or more substituents which are independently: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

Substituted heteroaryl also includes ring systems substituted with one or more oxide (—O—) substituents, such as, for example, pyridinyl N-oxides.

“Heterocycloalkyl” refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Whenever it appears herein, a numerical range such as “3 to 18” refers to each integer in the given range—e.g., “3 to 18 ring atoms” means that the heterocycloalkyl group may consist of 3 ring atoms, 4 ring atoms, etc., up to and including 18 ring atoms. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems. The heteroatoms in the heterocycloalkyl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl may be attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, a heterocycloalkyl moiety is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, —OR^a, —SR^a, —OC(O)—R^a, —N(R^a)₂, —C(O)R^a, —C(O)OR^a, —OC(O)N(R^a)₂, —C(O)N(R^a)₂, —N(R^a)C(O)OR^a, —N(R^a)C(O)R^a, —N(R^a)C(O)N(R^a)₂, N(R^a)C(NR^a)N(R^a)₂, —N(R^a)S(O)_tR^a (where t is 1 or 2), —S(O)_tR^a (where t is 1 or 2), —S(O)_tOR^a (where t is 1 or 2), —S(O)_tN(R^a)₂ (where t is 1 or 2), or PO₃(R^a)₂, where each R^a is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

“Heterocycloalkyl” also includes bicyclic ring systems wherein one non-aromatic ring, usually with 3 to 7 ring atoms, contains at least 2 carbon atoms in addition to 1-3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, as well as combinations comprising at least one of the foregoing heteroatoms; and the other ring, usually with 3 to 7 ring atoms, optionally contains 1-3 heteroatoms independently selected from oxygen, sulfur, and nitrogen and is not aromatic.

“Oxa” refers to the —O— radical.

“Oxo” refers to the =O radical.

“Moiety” refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule.

A “leaving group or atom” is any group or atom that will, under selected reaction conditions, cleave from the starting material, thus promoting reaction at a specified site. Examples of such groups, unless otherwise specified, include halogen atoms and mesyloxy, p-nitrobenzensulphonyloxy and tosyloxy groups.

“Protecting group” is intended to mean a group that selectively blocks one or more reactive sites in a multifunctional compound such that a chemical reaction can be carried out selectively on another unprotected reactive site and the group can then be readily removed or deprotected after the selective reaction is complete. A variety of protecting groups are disclosed, for example, in T. H. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons, New York (1999).

“Substituted” means that the referenced group may have attached one or more additional groups, radicals or moieties individually and independently selected from, for example, acyl, alkyl, alkylaryl, cycloalkyl, aralkyl, aryl, carbohydrate, carbonate, heteroaryl, heterocycloalkyl, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, ester, thiocarbonyl, isocyanato, thiocyanato, isothiocyanato, nitro, oxo, perhaloalkyl, perfluoroalkyl, phosphate, silyl, sulfinyl, sulfonyl, sulfonamidyl, sulfoxyl, sulfonate, urea, and amino, including mono- and di-substituted amino groups, and protected derivatives thereof. The substituents themselves may be substituted, for example, a cycloalkyl substituent may itself have a halide substituent at one or more of its ring carbons. The term “optionally substituted” means optional substitution with the specified groups, radicals or moieties.

For the avoidance of doubt, it is intended herein that particular features (for example integers, characteristics, values, uses, diseases, formulae, compounds or groups) described in conjunction with a particular aspect, embodiment or example of the invention are to be understood as applicable to any other aspect, embodiment or example described herein unless incompatible therewith. Thus such features may be used where appropriate in conjunction with any of the definition, claims or embodiments defined herein. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of the features and/or steps are mutually exclusive. The invention is not restricted to any details of any disclosed embodiments. The invention extends to any novel one, or novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Moreover, as used herein, the term “about” means that dimensions, sizes, formulations, parameters, shapes and other quantities and characteristics are not and need not be exact, but may be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, a dimension, size, formulation, parameter, shape or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. It is noted that embodiments of very different sizes, shapes and dimensions may employ the described arrangements.

Furthermore, the transitional terms “comprising”, “consisting essentially of” and “consisting of”, when used in the appended claims, in original and amended form, define the claim scope with respect to what unrecited additional claim elements or steps, if any, are excluded from the scope of the claim(s). The term “comprising” is intended to be inclusive or open-ended and does not exclude any additional, unrecited element, method, step or material. The term “consisting of” excludes any element, step or material other than those specified in the claim and, in the latter instance, impurities ordinary associated with the specified material(s). The term “consisting essentially of” limits the scope of a claim to the specified elements, steps or material(s) and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. All embodiments of the invention can, in the alternative, be more specifically defined by any of the transitional terms “comprising,” “consisting essentially of,” and “consisting of.”

Compounds, Polymers and Compositions

The catechol moiety is known for ensuring covalent bonds with the majority of hydroxylated substrates, and has been utilized as a linker. However, the use of catecholamine has several drawbacks, especially its rapid polymerization at a basic pH and spontaneous oxidation to quinones.

As depicted in reaction sequence A of Scheme 1 below, reactions between a surface and a volume (eg. a solution comprising the bromide compound) usually occur according to an S_N2 mechanism with the nucleophile almost always localized on the surface while the electrophile is located in the volume.

In contrast, the reaction sequence B of Scheme 1 cannot be completed due to electrostatic repulsions. The only super nucleophiles capable of displacing Br are the N₃⁻ and thiocyanate (SCN⁻) groups. Using compositions and methods described herein, the reaction sequence B becomes possible due to the particular reactivity of the C—Cl bond because of the enhanced reactivity of the C—Cl bond due to the presence of the electron withdrawing group (CO) in the alpha position.

The disclosure includes a series of novel compounds useful for grafting a large variety of compositions, such as polymers, onto a variety of surfaces. The disclosure also includes a series of novel catechol compounds useful for grafting a large variety of compositions, such as biomolecules and polymers including antimicrobial polymers and biomacromolecules, onto a variety of surfaces. In some embodiments, the compounds are derived from the catechol family, and are more stable than catecholamine which exhibits a propensity to polymerize.

In one aspect, the disclosure also includes the use of novel dipodal silane compounds. In some embodiments, the dipodal silane compounds are further substituted with an alkyl chain following treatment with an alkyl halide in a single step reaction to provide highly hydrophobic/hydrophilic compounds that are ready-to graft on a variety of suraces, such as hydroxylated or activated surfaces, with the benefit of being much more stable and extremely resistant to hydrolysis compared to the conventional silanes. See U.S. Pat. No. 9,029,491, US 20050187400, U.S. Pat. Nos. 8,475,782, and 9,289,534, all of which are incorporated by reference herein in their entireties.

The disclosure also includes novel ready-to-graft biocidal polymers and compounds that can be covalently attached to surfaces. These polymers and compounds can be used in biocidal and antimicrobial compositions that are useful to combat healthcare-acquired infections (HAI) and virtually any type of environmental surface treatment. The biocidal polymers and compounds of the disclosure can be used to contain and control the spread of infectious pathogens in a variety of health and industrial applications.

Substrates, such as nanoparticles, antibodies, enzymes, and compositions and polymers comprising the moieties of the disclosure are easily graftable and provide bonds with improved stability and less sensitivity to hydrolysis than other moieties, such as silane linkers.

In one aspect of the disclosure, the polymers are prepared by covalently linking the chemical moieties to the polymer to produce polymers that can be easily grafted onto a variety of surfaces, including metal and wood. In one aspect of the disclosure, graftable substrates, including polymers, antibodies, enzymes, and peptides, are prepared by covalently linking the compounds of the disclosure to a substrate that can be easily grafted onto a variety of surfaces, including metal and wood. In some embodiments, the compounds of the disclosure are easily graftable to surfaces. In some embodiments, a ready-to-graft solution of the compounds of the invention is prepared in a one-pot synthesis. In some embodiments, the graftable substrates of the disclosure are prepared in a one-pot synthesis. In some embodiments, the polymers are prepared in a one-pot synthesis. In another aspect of the disclosure, compounds described herein can be easily grafted onto surfaces. When grafted, functional groups on the chemical moieties and compounds of the disclosure form covalent bonds with functional groups on the surface.

Over the past decade, there has been a tremendous need for self-cleaning surfaces that was exacerbated following the advent of the COVID-19 pandemic. Indeed, transient solutions such as disinfecting wipes are labor-intensive, costly and not sustainable in the long term. In order to address the shortcomings of existing temporary solutions, numerous surface coating strategies were developed to confer long-lasting antimicrobial properties to environmental surfaces.

While metal-ion-based coatings have been shown to be effective, they raise concerns of durability, toxicity and sustainability. In contrast, quaternary ammonium compounds (QAC) have long been known as potent and stable antimicrobial products when used as surface coatings.

In the category of QAC, polymers were shown to be superior to monomers (classically C₁₈ quaternized alkyl chain such as 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride). The latter class of molecules was described in the early 1970s and sold by Dow-Corning from the late 1970s. The main reason for the low effectiveness of quaternary ammonium monomers is likely due to a surface charge density difference between monomers and polymers.

Indeed, quaternary ammonium polymers can be turned into high-density QACs, exceeding 10¹⁵ charges/cm², which is the most commonly described threshold to achieve biocidal activity of surfaces. These compounds kill bacteria, viruses, and fungi even as a monolayer, provided that the charge density threshold is reached. This is not the case with simple quaternary alkyl-ammonium compounds.

While numerous products are currently marketed as spray-on coatings, their active ingredient is almost always 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride or any similar compound that is a C₁₈ quaternized alkyl chain. It is now well established in the literature that these compounds are poorly effective. On a monolayer, they typically display only a bacteriostatic effect due to their low charge density. In order to overcome their weak efficiency on surfaces, they are often used in volume such as in blending techniques which typically ensure that the compounds are found throughout the entire thickness of the substrate. Coatings with thick multilayers of C₁₈ quaternized alkyl chains can kill bacteria due to their increased charge densities. In contrast, biocidal polymers typically kill bacteria, viruses, and fungi regardless of the coating thickness due to their spatial conformation as a polymer brush.

Bacterial infections, especially when associated with biofilm, represent one of the most serious complications following the implantation of medical devices. Surgical-site infections (SSIs) and periprosthetic joint injections (PJIs) are particularly devastating for orthopaedic patients as antibiotics can hardly reach dormant bacteria in low-nutrient microenvironment such as implant surfaces and bone. Biofilm is an exopolysaccharidic matrix comprising bacteria with reduced antibiotic sensitivity and poor mechanical accessibility. Biofilm formation plays a central role in the failure of conservative treatments (antibiotic use, irrigation, and debridement without implant removal) for implant-related infections (IRIs). Preventing biofilm formation has been recognized as a key element of surgical-site infections (SSI) and IRI prevention. Yet, in most medical disciplines, nothing new has been implemented in clinical practice that effectively reduces biofilm formation at the surface of implants. Bacterial biofilm is strongly associated with failure of infection control, infection recurrence, surgical revisions, poor patient outcomes (morbidity and mortality), and the development of chronic infections.

Despite significant improvements in hand-hygiene, the generalization of sterile personal protective equipment (PPE), and the systematic use of perioperative antiseptics and antibiotics, SSIs remain the most frequent complication reported after surgery even in industrialized nations. To this date, IRIs represent a major impediment to successful clinical outcomes. Overall, the catastrophic consequences of healthcare-acquired infections (HAIs) associated with surgical implants still represent a heavy burden on both patients and healthcare systems worldwide. Indeed, the implantation of medical devices has been growing steadily for the past few decades. In the same timeframe, the incidence of HAIs has been stable. Given that HAI incidence is tied to the total number of implantations, that demographic projections highlight the fast rise of obesity and diabetes (comorbidities that are known risk factors of SSIs) in aging industrialized nations, IRIs and SSIs are likely to become a “ticking time-bomb” for healthcare systems and a major obstacle to the use of medical devices in the near future. Patient risk profiles have also dramatically evolved over the past three decades. Indeed, there has been a significant surge in implantation rates even in elderly and cancer patients due to the improved safety of anesthesia and medical comorbidity optimization in the perioperative period. Due to the rapidly aging populations in industrialized countries, combined with the rising burden of obesity and diabetes, orthopaedic surgery procedures, especially in cancer patients, have been associated with persistently high SSI rates. Indeed, they range between 1% to 2% for elective joint reconstructions in healthy patients to up to 30% for orthopaedic oncology procedures. Another significant public health problem is the growing number of patients with permanent medical devices with numerous comorbidities. Indeed, having a “permanent” implant such as a total hip or knee replacement, cardiac valve, or spine instrumentation, can be seen as a lifetime risk to live with: the risk of late-onset infections or hematogenous spread of infection is real. Any urinary tract infection, dental procedure, or pneumonia, can become a life-changing event with serious and potentially fatal consequences. This is the rationale behind the clinical need for permanent antimicrobial protection of surfaces which transient eluting coatings cannot fully address by definition.

Although some progress has been made in preventing periprosthetic joint infections (PJI), their impact is dramatic and represents a turning point in patients' quality of life. In North America, the gold standard treatment for PJI is a two-stage exchange protocol where all the infected implants and surrounding soft tissues are removed and replaced by a temporary joint replacement (spacer). Antibiotic spacers have failed to drastically affect the landscape of PJI. Studies have raised concern regarding the following: (a) increasing microbial resistance, (b) insufficient antibiotic dose, (c) additional unnecessary costs, and (d) reduced mechanical properties of the commercial preparations. Moreover, there is evidence that the majority of bacteria are able to form biofilm on the surface of cement spacers. For infected total knee replacement (TKR), it has been shown that there was a cumulative incidence of reinfection of 14% at 5 years after reimplantation and a cumulative risk of revision of 22% at 10 years. Furthermore, when a two-stage protocol fails, the rate of success at definitively eradicating the infection dramatically falls, down to 0%, as shown in patients with comorbidities. Similarly, data showed that the cumulative risk of reinfection after a two-stage protocol exchange for infected total hip replacement (THR) was 14% at 5 years and the rate of death at final follow-up was 44%.

It has been shown that, in case of an infected THR, when a second two-stage protocol was performed after the first one failed, the rate of re-infection was as high as 42%. In case of a fungal infection, results are even worse. Data has shown a survivorship free of infection of 38% only. Latest data showed that hip and knee PJI are increasing in the United States. In 2017, the annual number of infected THR and TKR was 12,000 and 28,000, respectively. By 2030, the annual number of infected THR and TKR is expected to grow up to 20,000 and 40,000 respectively. The societal economic burden is tremendous and estimated to be $1.85 billion by 2030. Data from the American Joint Replacement Registry (AJRR) showed that infection is the number one cause of early and late failure for both hip and knee replacement. Lastly, recent data has shown that PJJ is estimated to be responsible for 15% of all revision hip and 25% of all revision knee procedures and is associated with a 5-year mortality rate higher than that of breast cancer, melanoma, Hodgkin's lymphoma, and several other common cancers. Therefore, despite best efforts of prevention, the number of primary THR and TKR leading to infection is still on the rise and dramatically affects patient quality of life with multiple revision surgeries, complications, long-term antibiotic therapy with associated side-effects, chronic pain, risk of infection recurrence, amputation, and death.

As every PJJ starts with a primary procedure, it appears appropriate to use a technology that can permanently modify the surface of primary implants in order to prevent infections from occurring in the first place. Useful antimicrobial surface protections should be able to support the following claims: prevention of implant-related infections, long-lasting protection of implant surfaces from late onset bacterial hematogenous spread, indirect decrease of surrounding tissue bacterial load by drastic biofilm inhibition, excellent local and systemic biocompatibility profile, stability (no release of potentially toxic compounds), full sterilizability, scalability, cost-effectiveness. Thus, in some aspects, the present disclosure provides materials, including polymers and compounds, useful for grafting on the surface of implants, including medical device implants for orthopaedic use.

Compounds

In one aspect, the disclosure provides a compound of formula (Ib):

wherein in formula (Ib):

X is halogen, optionally substituted amine, azido, or C(O)OR⁴; SR⁴, and

R⁴ is selected from hydrogen and optionally substituted alkyl.

In some embodiments, the compound of formula (Ib) is selected from:

In another aspect, the disclosure describes a compound of formula (XV):

wherein in formula (XV):each R⁵ is independently optionally substituted alkyl.

In some embodiments, each R⁵ is independently C₄-C₂₂ alkyl. In some embodiments, each R⁵ is independently C₁-C₂₂ alkyl.

In some embodiments, the compound of formula (XV) is a compound of formula (XVI):

wherein in formula (XVI):

each R⁵ is independently optionally substituted alkyl; and

n is an integer from 3 to 21.

In some embodiments, n is an integer from 15 to 19. In some embodiments, n is 17. In some embodiments, each R⁵ is methyl.

In some embodiments, the compound is a compound of formula (XVa):

In another aspect, the disclosure describes a compound of formula (XVII):

wherein in formula (XVII):

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl, optionally substituted aryl, optionally substituted alkenyl, or optionally substituted alkynyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, one R⁴ is methyl and one R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, each R⁴—CH₂(CH₂)₁₄CH₃. In some embodiments, each R⁴—CH₂(CH₂)₁₆CH₃. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, each R⁴ is independently selected from —CH₂CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19.

In another aspect, the disclosure describes a compound of formula (XVIIa):

wherein in formula (XVIIa):

n is an integer between 16 and 20; and

X is Br, Cl, or I.

In some embodiments, the compound of formula (XVIIa) is:

wherein X is a counterion. In some embodiments, X is Br.

In some embodiments, the compound of formula (XVIIa) is:

wherein X is a counterion. In some embodiments, X is Br.

In another aspect, the disclosure describes a compound of formula (XVIIb):

wherein in formula (XVIIb):

n is an integer between 15 and 19; and

X is Br, Cl, or I.

In another aspect, the disclosure describes a compound of formula (XVIIc):

wherein in formula (XVIIc):

each R⁴ is independently selected from optionally substituted alkyl, optionally substituted aryl, optionally substituted alkenyl, and optionally substituted alkynyl;

X is Br, Cl, or I. In some embodiments, each R⁴ is independently optionally substituted C₁₈-C₂₂ alkyl. In some embodiments, each R⁴—CH₂(CH₂)₁₄CH₃. In some embodiments, each R⁴—CH₂(CH₂)₁₆CH₃.

In another aspect, the disclosure describes a compound of formula (XVIII):

wherein in formula (XVIII):

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl, optionally substituted aryl, optionally substituted alkenyl, or optionally substituted alkynyl; v is an integer from 3 to 10;

w is an integer from 3 to 10; and

x is an integer from 1 to 4.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, x is 2. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, each R⁴ is independently C₁—C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, two R⁴ are methyl and two R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ and —CH₂(CF₂)_nCF₃, wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, each R⁴ is independently selected from —CH₂CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, each R⁴ is independently selected from —CH₂CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19.

In some embodiments, the compound of formula (XVIII) is a compound of formula (XVIIIa):

In another aspect, the disclosure describes a compound of formula (XIX):

wherein in formula (XIX):

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl, optionally substituted aryl, optionally substituted alkenyl, or optionally substituted alkynyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, In some embodiments, each R³ is methoxy. In some embodiments, R⁴ is C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, R⁴ is selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17. In some embodiments, R⁴ is selected from

In another aspect, the disclosure describes a compound of formula (XIXa):

wherein in formula (XIXa):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, In some embodiments, each R³ is methoxy.

In another aspect, the disclosure describes a compound of formula (XIXb):

In another aspect, the disclosure describes a compound of formula (XIXc):

wherein in formula (XIXc):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, In some embodiments, each R³ is methoxy.

In another aspect, the disclosure describes a compound of formula (XIXd):

In another aspect, the disclosure describes a compound of formula (XX):

wherein in formula (XX):

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl, optionally substituted aryl, optionally substituted alkenyl, or optionally substituted alkynyl;

v is an integer from 3 to 10;

w is an integer from 3 to 10; and

x is an integer from 1 to 4.

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, x is 2. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, two R⁴ are methyl and two R⁴ are independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, n is 16. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17.

In another aspect, the disclosure describes a compound of formula (XXa):

wherein in formula (XXa):

n is an integer from 16-20.

In one aspect, the disclosure describes compositions comprising at least one compound of the disclosure. In some embodiments, the compound is any one of a compound of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa). In some embodiments, the composition is an antibacterial composition. In some embodiments, the composition is a biocidal composition (eg. DBG21). In some embodiments, the composition is an antiviral composition. In some embodiments, the composition is an antifungal composition. In some embodiments, the composition is an antiprotozoal composition.

In one aspect, the disclosure describes a solution comprising an alcohol and at least one compound of the disclosure. In some embodiments, the compound is any one of a compound of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa). Any alcohol can be used, as understood by one of ordinary skill in the art. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the solution is an antibacterial solution. In some embodiments, the solution is a biocidal solution. In some embodiments, the solution is an antiviral solution. In some embodiments, the solution is an antifungal solution. In some embodiments, the solution is an antiprotozoal solution. In some embodiments, the solution is a ready-to-use solution for grafting.

Graftable Compounds and Substrates

In one aspect, the disclosure provides a graftable substrate comprising compounds and/or moieties of the invention. In some embodiments, the graftable substrate comprises at least one compound of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa). In some embodiments, the graftable substrate comprises at least one moiety of any one of formula (I) or formula (Ia). In some embodiments, the compound of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa) is grafted onto a substrate.

As would be understood by one of ordinary skill in the art, any substrate is contemplated by the disclosure. Non-limiting examples of substrates include polymers, antibodies, enzymes, peptides, and proteins.

In one aspect of the disclosure, the graftable substrate comprises at least one moiety of formula (I):

wherein in formula (I):

L is a single bond or a linking group.

In some embodiments, L is a single bond. In some embodiments, L is a linking group. The linking group may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group comprises optionally substituted amino, optionally substituted heterocyclyl, carboxyl, or optionally substituted thiol. In some embodiments, the linking group comprises a primary amino group, a secondary amino group, or a tertiary amino group. In some embodiments, the organic linker comprises dimethylamino, diethylamino, —C(O)O—, —S—, diethylcarboxylate, acetyl, optionally substituted triazole group, or optionally substituted tetrazole group.

In some embodiments, the moiety of formula (I) is a moiety of formula (Ia):

In another aspect, the graftable substrate comprises at least one moiety of formula (XVIa):

wherein in formula (XVIIa):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In another aspect, the graftable substrate comprises at least one moiety of formula (XVIIIa):

wherein in formula (XVIIIa):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10;

w is an integer from 3 to 10; and

x is an integer from 1 to 4.

In some embodiments, G is a single bond. In some embodiments, G is a linking group. The linking group G may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group comprises

In some embodiments, the linking group comprises

wherein each R⁴ is independently optionally substituted alkyl. In some embodiments, each R⁴ is independently selected from C₁-C₄ alkyl and

wherein each R³ is independently optionally substituted alkoxy, and v is an integer from 3 to 10. In some embodiments, each R⁴ is independently selected from methyl and

In some embodiments, one R₄ is methyl and one R⁴ is

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, x is 2. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, two R⁴ are methyl and two R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17.

In one aspect, the disclosure describes compositions comprising at least one graftable substrate of the disclosure. In some embodiments, the composition is an antibacterial composition. In some embodiments, the composition is a biocidal composition. In some embodiments, the composition is an antiviral composition. In some embodiments, the composition is an antifungal composition. In some embodiments, the composition is an antiprotozoal composition.

In one aspect, the disclosure describes a solution comprising an alcohol and at least one graftable substrate of the disclosure. Any alcohol can be used, as understood by one of ordinary skill in the art. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the solution is an antibacterial solution. In some embodiments, the solution is a biocidal solution. In some embodiments, the solution is an antiviral solution. In some embodiments, the solution is an antifungal solution. In some embodiments, the solution is an antiprotozoal solution. In some embodiments, the solution is a ready-to-use solution for grafting.

In one aspect, the disclosure provides methods for preparing a graftable substrate. In some embodiments, the disclosure includes methods for preparing a graftable substrate comprising a compound of any one of formula (XV), formula (XVI), or formula (XVa). In some embodiments, the disclosure includes methods for preparing a graftable substrate comprising a moiety of any one of formula (I) or formula (Ia).

In some embodiments, the method includes treating a substrate with a compound of formula (Ib):

wherein in formula (Ib):

X is halogen, optionally substituted amine, azido, cyano, —C(O)OR⁴; or —SR⁴, and

R⁴ is selected from hydrogen and optionally substituted alkyl.

In some embodiments, the compound of formula (Ib) is selected from:

In some embodiments, the method includes treating a substrate with one or more compounds of any one of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa).

In some embodiments, the substrate is selected from a polymer, an antibody, an enzyme, a peptide, and a protein. In some embodiments, the precursor polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide), poly(diallyldimethylammonium), or a C₃-C₂₂ alkyne. In some embodiments, the method further includes treating the precursor polymer with the compound of formula (Ib) in a solvent selected from ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the method further includes treating the precursor polymer with at least one optionally substituted C₄-C₂₂ alkyl halide.

Polymers

In one aspect, the disclosure provides polymers comprising a compound of the disclosure. In one aspect, the disclosure provides polymers comprising a moiety of the disclosure.

In one aspect, the disclosure describes a polymer comprising at least one moiety of formula (I):

wherein in formula (I):

L is a single bond or a linking group.

In some embodiments, L is a single bond. In some embodiments, L is a linking group. The linking group may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group comprises optionally substituted amino, optionally substituted heterocycle, optionally substituted thiol, or carboxylate. In some embodiments, the linking group comprises a primary amino group, a secondary amino group, or a tertiary amino group. In some embodiments, the organic linker comprises dimethylamino, diethylamino, —C(O)O—, —S—, diethylcarboxylate, acetyl, optionally substituted triazole group, optionally substituted maleic anor optionally substituted tetrazole group.

Any polymer is contemplated for use within the disclosure, as would be understood by one of ordinary skill in the art. In some embodiments, the polymer is a random copolymer. In some embodiments, the polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide) and poly(diallyldimethylammonium). In some embodiments, the polymer further comprises polyvinylpyridine (PVP) or polyethylenimine (PEI). In some embodiments, the polymer further comprises an optionally substituted C₄-C₂₂ alkyl group. In some embodiments, the polymer further comprises an optionally substituted C₃-C₂₂ alkyne. In some embodiments, the polymer further comprises an optionally substituted C₃-C₂₂ terminal alkyne. In some embodiments, the polymer is fully quaternized. In some embodiments, the polymer is partially quaternized. In some embodiment, the ratio of quaternized amines to non-quaternized amines is about 30% to about 50%. In some embodiments, the N+/N ratio is about 30% to about 50%.

In one embodiment, the moiety of formula (I) is a moiety of formula (Ia):

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (II):

In some embodiments, the polymer further comprises at least one moiety of formula (III):

wherein r is an integer from 3 to 20. In some embodiments, r is an integer from 3 to 11. In some embodiments, r is 3. In some embodiments, r is 9. In some embodiments, the polymer consists of moieties of formula (II) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (II) and moieties of formula (III).

In some embodiments, the polymer further comprises at least one fragment of formula (IV):

wherein in formula (IV):

r is an integer from 3 to 11. In some embodiments, r is 3. In some embodiments, r is 9.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (V):

wherein in formula (V):

each R² is independently optionally substituted alkyl. In some embodiments, each R² is independently a C₁-C₄ alkyl. In some embodiments, each R² is methyl. In some embodiments, the polymer comprises a mixture of meta and para substituents of formula (V).

In some embodiments, the moiety of formula (V) is a moiety of formula (VI):

In some embodiments, the polymer comprises a mixture of meta and para substituents of formula (VI).

In some embodiments, the polymer further comprises a moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl. In some embodiments, each R⁶ is independently a C₄-C₁₂ alkyl. In some embodiments, two R⁶ are methyl and one R⁶ is decyl. In some embodiments, the polymer comprises a mixture of meta and para substituents of formula (VII).

In some embodiments, the polymer consists of moieties of formula (V) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (V) and moieties of formula (VII). In some embodiments, the polymer consists of moieties of formula (VI) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (VI) and moieties of formula (VII).

In some embodiments, the polymer further comprises at least one moiety of formula (VIII):

wherein in formula (VIII):

each R⁶ is independently optionally substituted alkyl.

In some embodiments, each R⁶ is independently a C₄-C₁₂ alkyl. In some embodiments, two R⁶ are methyl and one R⁶ is decyl.

In another aspect, the disclosure describes a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXa), formula (IXb), or formula (IXh):

wherein in formula (IXa) and formula (IXb):

each R² is independently optionally substituted alkyl.

In some embodiments, each R² is independently methyl.

In some embodiments, the moiety of formula (IXa) is a moiety of formula (IXc):

In some embodiments, the moiety of formula (IXb) is a moiety of formula (IXd):

In some embodiments, the PEI polymer comprises moieties of formula (IXc) and moieties of formula (IXd). In some embodiments, the PEI polymer comprises moieties of formula (IXc), moieties of formula (IXd), and moieties of formula (IXh). In some embodiments, the polymer is branched, hyperbranched or linear. In some embodiments, the PEI polymer is fully alkylated. In some embodiments, the PEI polymer is fully methylated. An example of a fully methylated monomer is illustrated in FIG. 8. As would be understood by one of ordinary skill in the art, in a non-limiting example a PEI polymer comprises primary and secondary nitrogen atoms, and when fully methylated, all primary and secondary nitrogens are converted to tertiary nitrogens comprising two and one methyl groups, respectively. In a non-limiting embodiment, the tertiary nitrogens can be quaternized following treatment with catechol compounds described herein (such as Compounds 1001-1003), resulting in mixture of moieties of formula (IXc) and/or moieties of formula (IXd) and/or moieties of formula (IXh). In a non-limiting example, remaining tertiary nitrogens can be converted into quaternary nitrogens comprising an optionally substituted C₄-C₂₂ alkyl group, as would be understood by one of ordinary skill in the art. In some embodiments, the PEI polymer further comprises at least one optionally substituted C₄-C₂₂ alkyl group. In some embodiments, the PEI polymer is partially quaternized. In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the molar ratio of the total moieties of formula (IXa) and moieties of formula (IXb) to the optionally substituted C₄-C₂₂ alkyl group is about 0.05≤x≤0.5:(1-x). In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the molar ratio of the total moieties of formula (IXa) and moieties of formula (IXb) and moieties of formula (IXh) to the optionally substituted C₄-C₂₂ alkyl group is about 0.05≤x≤0.5:(1-x). In some embodiments, the PEI polymer consists of fully methylated monomers, wherein each monomer is fully quaternized and consists of moieties of formula (IXa), moieties of formula (IXb), and optionally substituted C₄-C₂₂ alkyl groups. In some embodiments, the PEI polymer consists of fully methylated monomers, wherein each monomer is fully quaternized and consists of moieties of formula (IXa), moieties of formula (IXb), moieties of formula (IXh), and optionally substituted C₄-C₂₂ alkyl groups. In some embodiments, the molar ratio of the total moieties of formula (IXa) and moieties of formula (IXb) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, the molar ratio of the total moieties of formula (IXa) and moieties of formula (IXb) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.1:0.9. In some embodiments, the molar ratio of the total moieties of formula (IXa), moieties of formula (IXb), and moieties of formula (IXh) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, the molar ratio of the total moieties of formula (IXa), moieties of formula (IXb), and moieties of formula (IXh) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.1:0.9. In some embodiments, the PEI polymer consists of fully methylated monomers, wherein each monomer is fully quaternized and consists of moieties of formula (IXc), moieties of formula (IXd), and optionally substituted C₄-C₂₂ alkyl groups. In some embodiments, the molar ratio of the total moieties of formula (IXc) and moieties of formula (IXd) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, the molar ratio of the total moieties of formula (IXc) and moieties of formula (IXd) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.1:0.9. In some embodiments, the PEI polymer consists of fully methylated monomers, wherein each monomer is fully quaternized and consists of moieties of formula (IXc), moieties of formula (IXd), moieties of formula (IXh), and optionally substituted C₄-C₂₂ alkyl groups. In some embodiments, the molar ratio of the total moieties of formula (IXc), moieties of formula (IXd), and moieties of formula (IXh) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, the molar ratio of the total moieties of formula (IXc), moieties of formula (IXd), and moieties of formula (IXh) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.1:0.9.

In another aspect, the disclosure describes a PEI polymer comprising at least one moiety of formula (IXe), or substructures thereof:

wherein in formula (IXe):

each R⁴ is independently optionally substituted alkyl; and

each R⁵ is independently optionally substituted alkyl or a moiety of formula (Ia):

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In some embodiments, each R⁴ is independently C₁-C₃ alkyl. In some embodiments, each R⁴ is methyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₅-C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₆ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₁₂ alkyl.

Non-limiting examples of substructures of formula (IXe) include:

In some embodiments, in formula (IXe), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ optionally substituted alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, in formula (IXe), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ optionally substituted alkyl groups is about 0.08≤x≤0.12:(1-x). In some embodiments, in formula (IXe), the PEI polymer is fully quaternized. In some embodiments, in formula (IXe), the molar ratio of number of R⁵ moieties of formula (Ia) to the number of R⁵ optionally substituted alkyl groups are is about 0.1:0.9. In some embodiments, in formula (IXe), the alkyl group is a C₁₀ group. In some embodiments, in formula (IXe), the alkyl group is a C₆ alkyl group.

In another aspect, the disclosure describes a PEI polymer comprising at least one moiety of formula (IXe1), or substructures thereof:

wherein in formula (IXe1):

each R⁴ is independently optionally substituted alkyl, or is absent; and

each R⁵ is independently optionally substituted alkyl, a moiety of formula (Ia)

or absent;with the proviso that at least one R⁵ is a moiety of formula (Ia):

and each nitrogen atom is trivalent or a quaternary nitrogen.

Non-limiting examples of substructures of formula (IXe1) include:

In some embodiments, each R⁴ is independently C₁-C₃ alkyl. In some embodiments, each R⁴ is methyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₅-C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₆ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₁₂ alkyl.

In another aspect, the disclosure describes a PEI polymer comprising at least one moiety of formula (IX), or a substructure thereof:

wherein in formula (IXf):

each R⁵ is independently C₁₀ alkyl or

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₁₀ alkyl. In some embodiments, in formula (IXf), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ C₁₀ group groups is about 0.05≤x≤0.5:(1-x). In some embodiments, in formula (IXf), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ C₁₀ alkyl groups is about 0.06≤x≤0.12:(1-x). In some embodiments, in formula (IXf), the PEI polymer is fully quaternized. In some embodiments, in formula (IXf), the molar ratio of number of R⁵ moieties of formula (Ia) to the number of R⁵ C₁₀ alkyl groups are is about 0.1:0.9.

Non-limiting examples of substructures of formula (IXf) include:

In some embodiments, PEI polymer comprises one or more of the following moieties, and one R² is methyl and one R² is hexyl:

In another aspect, the disclosure describes a PEI polymer comprising at least one moiety of formula (IXg):

wherein in formula (IXg):

each R⁵ is independently C₆ alkyl or

with the proviso that at least one R⁵ is a moiety of formula (Ia):

In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (Ia):

and the remaining R⁵ are C₆ alkyl. In some embodiments, in formula (IXg), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ C₆ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, in formula (IXg), the molar ratio of the number of R⁵ moieties of formula (Ia) to the number of R⁵ C₆ alkyl groups is about 0.06≤x≤0.12:(1-x). In some embodiments, in formula (IXg), the PEI polymer is fully quaternized. In some embodiments, in formula (IXg), the molar ratio of number of R⁵ moieties of formula (Ia) to the number of R⁵ C₆ alkyl groups is about 0.1:0.9.

Non-limiting examples of substructures of formula (IXg) include:

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XI):

wherein in formula (XI):

G is a single bond or linking group;

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10.

In some embodiments, G is a single bond. In some embodiments, G is a linking group. The linking group may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group comprises optionally substituted amino, optionally substituted heterocyclyl, or carboxylate. In some embodiments, the linking group comprises a primary amino group, a secondary amino group, or a tertiary amino group. In some embodiments, the organic linker comprises dimethylamino, diethylamino, —C(O)O—, diethylcarboxylate, acetyl, optionally substituted triazole group, or optionally substituted tetrazole group. In some embodiments, the linking group comprises

In some embodiments, the linking group comprises

wherein each R⁴ is independently optionally substituted alkyl. In some embodiments, each R⁴ is independently selected from C₁-C₄ alkyl and

wherein each R³ is independently optionally substituted alkoxy, and v is an integer from 3 to 10. In some embodiments, each R⁴ is independently selected from methyl and

In some embodiments, one R₄ is methyl and one R⁴ is

In some embodiments, the polymer is a random copolymer. In some embodiments, the polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide) and poly(diallyldimethylammonium). In some embodiments, the polymer further comprises polyvinylpyridine (PVP) or polyethylenimine (PEI). In some embodiments, the polymer further comprises an optionally substituted C₄-C₂₂ alkyl group. In some embodiments, the polymer further comprises an optionally substituted C₃-C₂₂ alkyne. In one embodiment, the optionally substituted C₃-C₂₂ alkyne is a terminal alkyne. In some embodiments, the polymer is partially quaternized. In some embodiments, the polymer is fully quaternized.

In some embodiments, v is 3.

In some embodiments, R³ is methoxy.

In another aspect, the disclosure describes polymer comprising at least one moiety of formula (XII) and at least one moiety of formula (XIII):

wherein in formula (XII):

r is an integer from 3 to 11;

wherein in formula (XIII):

each R³ is independently optionally substituted alkoxy; andv is an integer from 3 to 10;

with the proviso that when in formula (XIII) v is 3 and each R³ is methoxy, then in formula (XII) r is not 3.

In some embodiments, r is an integer from 4 to 11. In some embodiments, r is 9. In some embodiments, v is 3. In some embodiments, each R³ is methoxy. In some embodiments, the polymer consists of moieties of formula (XII) and moieties of formula (XIII). In some embodiments, the polymer is partially quaternized. In some embodiments, the polymer is fully Si(OMe)₃ quaternized. In some embodiments,

In some embodiments, the polymer comprises at least one moiety of formula (XIV):

In some embodiments, when v is 3 and each R³ is methoxy, then r is not 3.

In some embodiments, r is an integer from 3 to 11. In some embodiments, r is an integer from 4 to 11. In some embodiments, r is 9. In some embodiments, v is 3. In some embodiments, each R³ is methoxy. In some embodiments,

In another aspect, the disclosure describes a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa):

wherein in formula (XIa):

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10. In some embodiments, v is 3. In some embodiments, each R³ is methoxy. In some embodiments, is

In another aspect, the disclosure describes a polyethylenimine (PEI) polymer comprising at least one of the following moieties of formula (XIa):

wherein each R² is independently optionally substituted alkyl. In some embodiments, R² is methyl. In some embodiments, each R² is independently selected from methyl and hexyl. In some embodiments, the polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa) is fully quaternized. In some embodiments, the polyethylenimine (PEI) polymer comprises at least one of the following moieties of formula (XIa):

wherein R² is independently optionally substituted alkyl, optionally wherein R² is hexyl. In some embodiments, fully quaternized refers to a polymer wherein at least 95%, 96%, 97%, 98%, 99%, or greater than 99% of nitrogen atoms are quaternized.

In some embodiments, the PEI polymer comprises at least one moiety of formula (XIa) and at least one hexyl moiety and the molar ratio of the number of moieties of formula (XIa) to the number of hexyl moieties is about 0.05≤x≤0.5:(1-x) or about 0.06≤x≤0.12:(1-x). In some embodiments, the PEI polymer comprises at leat one moiety of formula (XIa) and at least one hexyl moiety and the molar ratio of the number of moieties of formula (XIa) to the number of hexyl moieties is about 0.1:0.9. In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the PEI polymer is fully quaternized with methyl moieties.

In some embodiments, the PEI polymer comprises one or more of the following moiety, wherein one R² is hexyl and one R² is methyl:

In another aspect, the moiety of formula (XIa) is a moiety of formula (XIb):

wherein in formula (XIb):

each R⁴ is independently optionally substituted alkyl; and

each R⁵ is independently optionally substituted alkyl or a moiety of formula (XIa):

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10,

with the proviso that at least one R⁵ is a moiety of formula (XIa):

In some embodiments, v is 3. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁-C₃ alkyl. In some embodiments, each R⁴ is methyl. In some embodiments, each moiety of formula (XIa) is

In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (XIa):

and the remaining R⁵ are C₅-C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are moieties of formula (XIa):

and the remaining R⁵ are C₆ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are

and the remaining R⁵ are C₆ alkyl.

Non-limiting examples of substructures of formula (IXb) include:

In some embodiments, the polyethylenimine (PEI) polymer comprises one or more substructures of formula (IXb).

In some embodiments, in formula (XIb), the molar ratio of the number of R⁵ moieties of formula (XIa) to the number of R⁵ optionally substituted alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, in formula (XIb), the molar ratio of the number of R⁵ moieties of formula (XIa) to the number of R⁵ optionally substituted alkyl groups is about 0.06≤x≤0.12:(1-x). In some embodiments, in formula (XIb), the PEI polymer is fully quaternized. In some embodiments, in formula (XIb), the molar ratio of number of R⁵ moieties of formula (XIa) to the number of R⁵ optionally substituted alkyl groups are is about 0.1:0.9. In some embodiments, in formula (XIb), the alkyl group is C₆ alkyl.

In another aspect, the disclosure describes a PEI polymer comprising at least one moiety of formula (IXb1), or substructures thereof:

wherein in formula (IXb1):

each R⁴ is independently optionally substituted alkyl, or absent; and

each R⁵ is independently optionally substituted alkyl, a moiety of formula (XIa):

or absent;

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10;

with the proviso that at least one R⁵ is a moiety of formula (XIa):

and each nitrogen atom is trivalent or a quaternary nitrogen.

Non-limiting examples of substructures of formula (IXb1) include:

In some embodiments, the polyethylenimine (PEI) polymer comprises one or more substructures of formula (IXb1).

In another aspect, the moiety of formula (XIa) is a moiety of formula (XIc):

wherein in formula (XIc):

each R⁵ is independently C₆ alkyl or

each R³ is independently optionally substituted alkoxy; and

v is an integer from 3 to 10,

with the proviso that at least one R⁵ is

In some embodiments, v is 3. In some embodiments, each R³ is methoxy. In some embodiments,

In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are

and the remaining R⁵ are C₅-C₁₀ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are

and the remaining R⁵ are C₆ alkyl. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 R⁵ are

and the remaining R⁵ are C₆ alkyl.

Non-limiting examples of substructures of formula (IXf) include:

In some embodiments, the polyethylenimine (PEI) polymer comprises one or more substructures of formula (IXf).

In some embodiments, in formula (XIc), the molar ratio of the number of R⁵ moieties of formula (XIa) to the number of R⁵ C₆ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, in formula (XIc), the molar ratio of the number of R⁵ moieties of formula (XIa) to the number of R⁵ C₆ alkyl groups is about 0.06≤x≤0.12:(1-x). In some embodiments, in formula (XIc), the PEI polymer is fully quaternized. In some embodiments, in formula (XIc), the molar ratio of the number of R⁵ moieties of formula (XIa) to the number of R⁵ C₆ alkyl groups is about 0.1:0.9.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIa):

wherein in formula (XVIIa):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIIIa):

wherein in formula (XVIIIa):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

each R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10;

w is an integer from 3 to 10; and

x is an integer from 1 to 4.

In some embodiments, G is a single bond. In some embodiments, G is a linking group. The linking group may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group comprises

In some embodiments, the linking group comprises

In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, x is 2. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, each R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, two R⁴ are methyl and two R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, each R⁴ is independently selected from —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, each R⁴ is independently selected from —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIIh):

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIIb):

wherein in formula (XVIIb):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, the linking group comprises

In some embodiments, the linking group comprises

In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, R⁴ is C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is methyl. In some embodiments, R⁴ is selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17. In some embodiments, w is 3. In some embodiments, v is 3.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIIj):

wherein in formula (XVIIj):

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, each R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, each R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, R⁴ is methyl. In some embodiments, R⁴ is selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17. In some embodiments, w is 3. In some embodiments, v is 3.

In some embodiments, the polymer further comprises at least one moiety of formula (III):

wherein r is an integer from 3 to 20. In some embodiments, r is an integer from 3 to 11. In some embodiments, r is 3. In some embodiments, the polymer consists of moieties of formula (XVIIb) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (XVIIb) and moieties of formula (III). In some embodiments, the polymer consists of moieties of formula (XVIIj) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (XVIIj) and moieties of formula (III).

In some embodiments, the polymer comprises at least one moiety of of formula (XVIId):

wherein in formula (XVIIc):

G is a single bond or a linking group;

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

r is an integer from 3 to 11;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, the linking group comprises

In some embodiments, the linking group comprises

In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, R⁴ is methyl. In some embodiments, R⁴ is selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17. In some embodiments, w is 3. In some embodiments, v is 3.

In some embodiments, the moiety of formula (XVIIb) is a moiety of formula (XVIId):

In some embodiments, the polymer consists of moieties of formula (XVIId) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (XVIId) and moieties of formula (III).

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XVIIe):

wherein in formula (XVIIe):

each R³ is independently optionally substituted alkoxy;

R⁴ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, R⁴ is independently C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is C₁-C₂₂ alkyl or C₁-C₂₂ haloalkyl. In some embodiments, R⁴ is independently C₁₈ alkyl or C₁₈ haloalkyl. In some embodiments, R⁴ is independently C₁₆ alkyl or C₁₆ haloalkyl. In some embodiments, R⁴ is methyl. In some embodiments, R⁴ is selected from —CH₂(CH₂)_nCH₃ and —CH₂CH₂(CF₂)_nCF₃, wherein n is an integer from 15 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is an integer from 14 to 20. In some embodiments, R⁴ is —CH₂(CH₂)_nCH₃ wherein n is 14, 16, 18, or 20. In some embodiments, n is 14. In some embodiments, n is 16. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is an integer from 15 to 19. In some embodiments, R⁴ is —CH₂CH₂(CF₂)_nCF₃ wherein n is 15, 17, or 19. In some embodiments, n is 15. In some embodiments, n is 17. In some embodiments, w is 3. In some embodiments, v is 3.

In some embodiments, the moiety of formula (XVIIe) is a moiety of formula (XVIIf):

wherein in formula (XVIIf):

each R² is independently optionally substituted alkyl. In some embodiments, each R² is independently a C₁-C₄ alkyl.

In some embodiments, the polymer further comprises a moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl. In some embodiments, each R⁶ is independently a C₄-C₁₂ alkyl. In some embodiments, two R⁶ are methyl and one R⁶ is decyl.

In some embodiments, the polymer further comprises at least one moiety of formula (XVIIg):

wherein in formula (XVIIg):

each R³ is independently optionally substituted alkoxy;

each R⁴ and R⁶ is independently optionally substituted alkyl;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, each R³ is independently a C₄-C₁₂ alkyl. In some embodiments, two R³ are methyl and one R³ is decyl. In some embodiments, w is 3. In some embodiments, v is 3.

In some embodiments, the polymer consists of moieties of formula (XVIIe) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (XVIIe) and moieties of formula (VII). In some embodiments, the polymer consists of moieties of formula (XVIIf) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (XVIIf) and moieties of formula (VII).

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XXI):

wherein in formula (XXI):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, the at least one moiety of formula (XXI) is covalently bonded to an amine moiety of the polymer. In some embodiments, the at least one moiety of formula (XXI) is covalently bonded to a quaternizable amine moiety of the polymer. In some embodiments, the at least one moiety of formula (XXI) is covalently bonded to a tertiary amine moiety of the polymer. Any polymer comprising one or more tertiary amine moieties and/or one or more quaternizable nitrogens can further comprise a moiety of formula (XXI), thereby forming a quaternary amine moiety. Non-limiting examples of suitable polymers comprising tertiary amines include polyvinylpyridine and alkylated polyethylenimine (PEI) (e.g. methylated PEI), poly(n-vinyl imidazole), polylysine, poly[2 (dimethylamino)ethyl methacrylate], Poly(vinyl benzyl amine), poly(vinyl methyl benzylamine), polyvinyldimethylbenzylamine, and hydrolyzed polyvinylpyrrolidone.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XXIa):

wherein in formula (XXIa):

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10.

In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, w is 3. In some embodiments, v is 3.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XXIb):

In some embodiments, the polymer further comprises at least one moiety of formula (III):

wherein r is an integer from 3 to 20. In some embodiments, r is an integer from 3 to 11. In some embodiments, r is 3. In some embodiments, the polymer consists of moieties of formula (XXIa) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (XXIa) and moieties of formula (III). In some embodiments, the polymer consists of moieties of formula (XXIb) and moieties of formula (III). In some embodiments, the polymer comprises moieties of formula (XXIb) and moieties of formula (III).

In some embodiments, the polymer comprises at least one moiety of formula (XXId):

wherein in formula (XXId):

r is an integer from 3 to 11. In some embodiments, w is 3. In some embodiments, v is 3. In some embodiments, r is 3. In some embodiments, r is 9.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (XXII):

wherein in formula (XXII):

each R² is independently optionally substituted alkyl;

each R³ is independently optionally substituted alkoxy;

v is an integer from 3 to 10; and

w is an integer from 3 to 10. In some embodiments, each R² is independently a C₁-C₄ alkyl. In some embodiments, each R² is methyl. In some embodiments, the polymer comprises a mixture of meta and para substituents of formula (XXII). In some embodiments, each R³ is independently optionally substituted methoxy. In some embodiments, each R³ is methoxy. In some embodiments, w is 3. In some embodiments, v is 3.

In some embodiments, the moiety of formula (XXII) is a moiety of formula (XXIIa):

wherein in formula (XXII):

each R² is independently optionally substituted alkyl. In some embodiments, each R² is independently a C₁-C₄ alkyl. In some embodiments, each R² is methyl.

In some embodiments, the moiety of formula (XXII) is a moiety of formula (XXIIb):

In some embodiments, the polymer further comprises a moiety of formula (VII):

wherein in formula (VII):

each R⁶ is independently optionally substituted alkyl. In some embodiments, each R⁶ is independently a C₄-C₁₂ alkyl. In some embodiments, two R⁶ are methyl and one R³ is decyl.

In some embodiments, the polymer consists of moieties of formula (XXII) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (XXII) and moieties of formula (VII). In some embodiments, the polymer consists of moieties of formula (XXIIa) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (XXIIa) and moieties of formula (VII). In some embodiments, the polymer consists of moieties of formula (XXIIb) and moieties of formula (VII). In some embodiments, the polymer comprises moieties of formula (XXIIb) and moieties of formula (VII).

In some embodiments, the polymer further comprises at least one moiety of formula (XXIIc):

In some embodiments, each R³ is independently a C₄-C₁₂ alkyl. In some embodiments, two R³ are methyl and one R³ is decyl.

In some embodiments, the PEI polymer is branched, hyperbranched or linear. In some embodiments, the PEI polymer is fully methylated. An example of a fully methylated monomer is illustrated in FIG. 8. In some embodiments, the PEI polymer further comprises at least one optionally substituted C₄-C₂₂ alkyl group. In some embodiments, the polymer is partially quaternized. In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the molecular weight of the PEI polymer has a molecular weight in a range of about 160 kDa and about 750 kDa. In some embodiments, the molecular weight of the PEI polymer has a molecular weight of about 160 kDa, about 170 kDa, about 180 kDa, about 190 kDa, about 200 kDa, about 210 kDa, about 220 kDa, about 230 kDa, about 240 kDa, about 250 kDa, about 260 kDa, about 270 kDa, about 280 kDa, about 290 kDa, about 300 kDa, about 310 kDa, about 320 kDa, about 330 kDa, about 340 kDa, about 350 kDa, about 360 kDa, about 370 kDa, about 380 kDa, about 390 kDa, about 400 kDa, about 410 kDa, about 420 kDa, about 430 kDa, about 440 kDa, about 450 kDa, about 460 kDa, about 470 kDa, about 480 kDa, about 490 kDa, about 400 kDa, about 510 kDa, about 520 kDa, about 530 kDa, about 540 kDa, about 550 kDa, about 560 kDa, about 570 kDa, about 580 kDa, about 590 kDa, about 600 kDa, about 610 kDa, about 620 kDa, about 630 kDa, about 640 kDa, about 650 kDa, about 660 kDa, about 670 kDa, about 680 kDa, about 690 kDa, about 700 kDa, about 710 kDa, about 720 kDa, about 730 kDa, about 740 kDa, or about 750 kDa.

In some embodiments, the molar ratio of the moieties of formula (XIa) to the optionally substituted C₄-C₂₂ alkyl group is about 0.05≤x≤0.5:(1-x). In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the PEI polymer consists of fully methylated monomers, wherein each monomer is fully quaternized and consists of moieties of formula (XIa) and optionally substituted C₄-C₂₂ alkyl groups. In some embodiments, the ratio of the total moieties of formula (XIa) to the optionally substituted C₄-C₂₂ alkyl groups is about 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XIa) to the optionally substituted C₄-C₂₂ alkyl groups are present in a molar ratio of about 0.1:0.9. In some embodiments, the C₄-C₂₂ alkyl group is a C₁₀ group. The amount of a particular moiety or monomer, whether the relative amount or a quantitative amount, present in a polymer or copolymer as described herein, can be determined and described using methods as understood by one of ordinary skill in the art. In one embodiment, the amount of each moiety present in a polymer is described by its molar ratio. In some embodiments, the molar ratio is 0.05, 0.06, 0.07, 0.08, 0.09, 0.11, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17. 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.40, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49, or 0.50. In some embodiments, the molar ratio is 0.05≤x≤0.5. In some embodiments, the molar ratio is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (I) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (II) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (III) is 0.5≤x≤0.95. In some embodiments, the molar ratio of formula (V) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (VI) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (VII) is 0.5≤x≤0.95. In some embodiments, the molar ratio of formula (IX) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (IXa) is 0.05≤x≤0.5. In some embodiments, the molar ratio of formula (XI) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XII) is 0.8≤x≤0.95. In some embodiments, the molar ratio of formula (XIII) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XIa) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XXIa) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XXIb) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XXII) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XXIIa) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XXIIb) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XVIIe) is 0.05≤x≤0.2. In some embodiments, the molar ratio of formula (XVIIf) is 0.05≤x≤0.2. In some embodiments, a polymer comprises two different moieties, and the moieties are present in a ratio of 0.05≤x≤0.5:(1-x) or 0.05≤x≤0.2:(1-x). In some embodiments, x is 0.05, 0.06, 0.07, 0.08, 0.09, 0.11, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17. 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.40, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49, or 0.50. In some embodiments, the moieties of formula (II) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In one embodiment, the moieties of formula (II) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.2:(1-x). In one embodiment, the moieties of formula (II) and moieties of formula (III) are present in a molar ratio of about 0.06:0.94. In some embodiments, the moieties of formula (V) and moieties of formula (VII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In one embodiment, the moieties of formula (V) and moieties of formula (VII) are present in a molar ratio of 0.05≤x≤0.2:(1-x). In one embodiment, the moieties of formula (V) and moieties of formula (VII) are present in a molar ratio of about 0.1:0.9. In some embodiments, the moieties of formula (VI) and moieties of formula (VII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In one embodiment, the moieties of formula (VI) and moieties of formula (VII) are present in a molar ratio of 0.05≤x≤0.2:(1-x). In one embodiment, the moieties of formula (VI) and moieties of formula (VII) are present in a molar ratio of about 0.1:0.9. In some embodiments, the moieties of formula (XII) and moieties of formula (XIII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XII) and moieties of formula (XIII) are present in a molar ratio of about 0.05:0.95. In one embodiment, the moieties of formula (XII) and moieties of formula (XIII) are present in a molar ratio of 0.05≤x≤0.2:(1-x). In some embodiments, the molar ratio is 0.05:0.95. In some embodiments, the molar ratio is about 0.1:0.9. In some embodiments, the molar ratio is about 0.06:0.94. In some embodiments, the moieties of formula (XXIa) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIb) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIa) and moieties of formula (III) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXIb) and moieties of formula (III) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXII) and moieties of formula (VIII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIIa) and moieties of formula (VIII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIIb) and moieties of formula (VIII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXII) and moieties of formula (VIII) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXII) and moieties of formula (VIII) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXIIb) and moieties of formula (VIII) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XVIIb) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XVIIb) and moieties of formula (III) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XVIId) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XVIId) and moieties of formula (III) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XVIIe) and moieties of formula (VII) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XVIIe) and moieties of formula (VII) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXIa) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIa) and moieties of formula (III) are present in a molar ratio of about 0.10:0.90. In some embodiments, the moieties of formula (XXIb) and moieties of formula (III) are present in a molar ratio of 0.05≤x≤0.5:(1-x). In some embodiments, the moieties of formula (XXIb) and moieties of formula (VII) are present in a molar ratio of about 0.10:0.90.

In some embodiments, each R⁵ is independently C₄-C₂₂ alkyl.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (Ie):

wherein in formula (Ie):

L is a single bond or an organic linker;

each R¹ is OH; and

s is an integer from 0 to 3.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (IIb):

wherein in formula (II):

R¹ OH; and

s is an integer from 0 to 3.

In another aspect, the disclosure describes a polymer comprising at least one moiety of formula (VIa):

wherein in formula (VIa):

R¹ is OH;

each R² is independently optionally substituted alkyl; and

s is an integer from 0 to 3.

In another aspect, the disclosure describes a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXaa):

wherein in formula (IXaa):

R¹ is OH;

each R² is independently optionally substituted alkyl; and

s is an integer from 0 to 3.

In one aspect, the disclosure describes a compound of formula (Ic):

wherein in formula (Ic):

X is halogen, optionally substituted amine, azido, cyano, or —C(O)OR⁴; and

R¹ is OH;

R⁴ is selected from hydrogen and optionally substituted alkyl; and

s is an integer from 0 to 3.

In one aspect, the disclosure describes a method for preparing a polymer of the disclosure, the method comprising treating a precursor polymer with a compound of formula (Ic).

In one aspect, the disclosure describes a method for preparing a graftable substrate, the method comprising treating a substrate with a compound of formula (Ic).

In one aspect, the disclosure describes a compound of formula (XVa):

wherein in formula (XVa):

R¹ is OH;

each R⁵ is independently optionally substituted alkyl; and

s is an integer from 0 to 3.

In some embodiments, the polymer is a random copolymer. In some embodiments, the polymer comprises polyvinylpyridine or polyvinylbenzyl chloride. In one aspect, the disclosure describes compositions comprising at least one polymer of the disclosure. In one aspect, the disclosure describes compositions comprising at least one compound of the disclosure. In some embodiments, the composition is an antibacterial composition. In some embodiments, the composition is a biocidal composition. In some embodiments, the composition is an antiviral composition. In some embodiments, the composition is an antifungal composition. In some embodiments, the composition is an antiprotozoal composition.

In one aspect, the disclosure describes a solution comprising an alcohol and at least one polymer of the disclosure. In one aspect, the disclosure describes a solution comprising an alcohol and at least one compound of the disclosure. Any alcohol can be used, as understood by one of ordinary skill in the art. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the solution is an antibacterial solution. In some embodiments, the solution is a biocidal solution. In some embodiments, the solution is an antiviral solution. In some embodiments, the solution is an antifungal solution. In some embodiments, the solution is an antiprotozoal solution. In some embodiments, the solution is a ready-to-use solution for grafting.

In one aspect of the disclosure, methods for preparing the polymers described herein are provided. In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa).

In one aspect of the disclosure, methods for preparing the compounds described herein are provided. In some embodiments, the compound is a compound of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa).

In one aspect, the disclosure describes a method for preparing a polymer of the disclosure, the method comprising treating a precursor polymer with a compound of formula (Ib):

wherein in formula (Ib):

X is halogen, optionally substituted amine, azido, cyano, —SR⁴—, or —C(O)OR⁴; and

R⁴ is selected from hydrogen and optionally substituted alkyl.

In some embodiments, R⁴ is methyl or ethyl.

In some embodiments, the compound of formula (Ib) is selected from:

The precursor polymer is not limited, as would be understood by one of ordinary skill in the art. In some embodiments, the precursor polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide), poly(diallyldimethylammonium), or a C₃-C₂₂ alkyne. In one embodiment, the precursor polymer is fully methylated PEI.

In some embodiments, the polymer is selected from polyvinylpyridine (PVP) and polyethylenimine (PEI), and the compound of formula (Ib) is selected from Compound 1001, Compound 1002, and Compound 1003.

In some embodiments, the polymer is polyvinylbenzylchloride, and the compound of formula (Ib) is selected from Compound 1005 and Compound 1006.

In some embodiments, the polymer comprises a C₃-C₂₂ alkyne, and the compound of formula (Ib) is Compound 1004.

In some embodiments, the polymer comprises a cyano group, and the compound of formula (Ib) is Compound 1004.

In some embodiments, the polymer comprises a carboxyl group, and the compound of formula (Ib) is Compound 1005.

In some embodiments, the polymer comprises an azido group, and the compound of formula (Ib) is Compound 1007.

In some embodiments, the polymer comprises an amino group, and the compound of formula (Ib) is Compound 1008.

In some embodiments, the polymer comprises a thio group, and the compound of formula (Ib) is Compound 1009.

In some embodiments, the method further comprises treating the precursor polymer with the compound of formula (Ib) in a solvent. In some embodiments, the solvent is an alcohol. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

In some embodiments, the method further comprises treating the precursor polymer with at least one optionally substituted C₄-C₂₂ alkyl halide. In some embodiments, the C₄-C₂₂ alkyl halide is a C₄ alkyl halide. In some embodiments, the C₄-C₂₂ alkyl halide is a C₆ alkyl halide In some embodiments, the C₄-C₂₂ alkyl halide is a C₁₀ alkyl halide.

In another aspect, the disclosure describes a method for preparing polymers disclosed herein. In one aspect, the disclosure describes a method for preparing a polymer comprising treating a precursor polymer with a compound of formula (XIa):

Y—(CH₂)_vSi(R³)₃   formula (XIa)

wherein in formula (XIa):

Y is halogen, optionally substituted amine, cyano, azido, or —C(O)OR⁴;

each R³ is independently optionally substituted optionally substituted alkoxy;

R⁴ is selected from hydrogen and optionally substituted alkyl; and

v is an integer from 3 to 10.

In some embodiments, R³ is methoxy. In some embodiments, R⁴ is methyl or ethyl. In some embodiments, v is 3. In some embodiments, Y is

In some embodiments, the compound of formula (XIa) is selected from I(CH₂)₃Si(OMe)₃, N₃(CH₂)₃Si(OMe)₃, H₂N(CH₂)₃Si(OMe)₃, or (CH₃)₂N(CH₂)₃Si(OMe)₃.

In another aspect, the disclosure describes a method for preparing polymers disclosed herein. In one aspect, the disclosure describes a method for preparing a polymer comprising treating a precursor polymer with a compound of any one of formula (XVII), formula (XVIII), formula (XIX), or formula (XX).

The precursor polymer is not limited, as would be understood by one of ordinary skill in the art. In some embodiments, the precursor polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide), poly(diallyldimethylammonium), or a C₃-C₂₂ alkyne. In one embodiment, the precursor polymer is fully methylated PEI.

In some embodiments, the polymer is selected from polyvinylpyridine (PVP) and polyethylenimine (PEI), and the compound of formula (XIa) is I(CH₂)₃Si(OMe)₃.

In some embodiments, the polymer is polyvinylbenzylchloride, and the compound of formula (XIa) is selected from H₂N(CH₂)₃Si(OMe)₃ and (CH₃)₂N(CH₂)₃Si(OMe)₃.

In some embodiments, the polymer comprises a C₃-C₂₂ alkyne, and the compound of formula (XIa) is N₃(CH₂)₃Si(OMe)₃.

In some embodiments, the polymer comprises a cyano group, and the compound of formula (XIa) is N₃(CH₂)₃Si(OMe)₃.

In some embodiments, the polymer comprises a carboxyl group, and the compound of formula (XIa) is H₂N(CH₂)₃Si(OMe)₃.

In some embodiments, the method further comprises treating the precursor polymer with the compound of formula (XIa) in a solvent. In some embodiments, the solvent is an alcohol. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

In some embodiments, the method further comprises treating the precursor polymer with at least one optionally substituted C₄-C₂₂ alkyl halide. In some embodiments, the C₄-C₂₂ alkyl halide is a C₁₀ alkyl halide.

In another aspect, the disclosure describes a method for preparing a compound of the disclosure. In some embodiments, the method comprising treating (R⁵)₃N with a compound of formula (Ib), wherein each R⁵ is independently optionally substituted alkyl:

wherein in formula (Ib):

X is halogen;

and wherein in (RS)₃N, each R⁵ is independently optionally substituted alkyl.

In some embodiments, the compound of formula (Ib) is selected from:

Grafting Enhancers and Grafting Adjuvants

The disclosure provides in one aspect grafting enhancers and/or grafting adjuvants. In some embodiments, the grafting enhancers and/or grafting adjuvants are useful to maximize the number of grafting sites for deposition of a graftable substrate, polymer, and/or compound on a surface, and also to improve the grafting robustness of the graftable substrate, polymer, and/or compound. some embodiments, the grafting enhancers and grafting adjuvants include cross-linking agents. See, for example, FIG. 48, which shows a schematic of a non-limiting example of deposition, covalent grafting, and cross-linking of a polymer (e.g. 3-trimethoxypropylsilyl-cohexyl-methylatedPEI) with a grafting enhancer and/or grafting adjuvant (e.g. a cross-linking reagent) on hydroxylated or activated surfaces. As shown in FIG. 48, the polymeric chain can form covalent bonds (for example, at a silane group of the polymeric chain) with the grafting enhancer and/or grafting adjuvant to provide additional grafting sites for the polymer (or graftable substrate or compound) to covalently bond to the surface. As would be understood by one of ordinary skill in the art, this exemplary scheme could be used with any graftable substrate, polymer, compound, or composition disclosed herein and any grafting enhancers and/or grafting adjuvants. In a non-limiting embodiment, the polymer is a partially silanized polymer. In some embodiments, a partially silainzed polymer refers to a polymer comprising silanized monomers in an amount of about 90%, about 85%, about 80%, 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% or less of the total monomers. In some embodiments, the cross-linking reagent is a silicate and/or a silane compound. Non-limiting examples of silicate compounds include tetramethylorthosilicate (tetramethoxysilane), trimethylmethoxyorthosilicate, trimethylethoxyorthosilicate, dimethyldimethoxyorthosilicate, dimethyldiethoxyorthosilicate, methyltrimethoxyorthosilicate, methyltriethoxyorthosilicate, tetramethoxyorthosilicate, tetraethoxyorthosilicate (tetraethoxysilane), methyldimethoxyorthosilicate, methyldiethoxyorthosilicate, dimethylethoxyorthosilicate, dimethylvinylmethoxyorthosilicate, dimethylvinylethoxyorthosilicate, tetraethylorthosilicate, methylvinyldimethoxyorthosilicate, methylvinyldiethoxyorthosilicate, diphenyldimethoxyorthosilicate, diphenyldiethoxyorthosilicate, phenyltrimethoxyorthosilicate, phenyltriethoxyorthosilicate, octadecyltrimethoxyorthosilicate, octadecyltriethoxyorthosilicate, 1,3-Disiloxanediol, 1,1,3,3-tetramethyl, 1,1,3,3-tetramethyldisiloxane-1,3-diol, 1,1,3,3-tetramethoxy-1,3-dimethyldisiloxane, tetraethoxy-1,3-dimethyldisiloxane, and 1,5-diethoxyhexamethyltrisiloxane. In some embodiments, the grafting enhancer and/or grafting adjuvant is a compound of the following formula:

wherein R¹ is at each occurrence independently selected from —OH, —C₁-C₁₀alkyl, and —C₁-C₁₀alkoxy; and n is an integer from 0-10.

In some embodiments, the grafting enhancer is a compound of the following structure, wherein R is a spacer:

In one aspect, the disclosure provides a composition comprising a compound, polymer and/or graftable substrate of the disclosure and at least one grafting enhancer and/or grafting adjuvant. In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is a cross-linking reagent. In some embodiments, the polymer and/or the compound of the disclosure is cross-linked with the grafting enhancer and/or grafting adjuvant. In some embodiments, the compound, polymer and/or graftable substrate is selected from formula (XVIIa), formula (XVIIIa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (III), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), optionally selected from any one of formula (XVII), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), or optionally any one of formula (I), formula (Ia), formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (II), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XVa).

In one aspect, the disclosure describes a solution comprising at least one grafting enhancer and/or grafting adjuvant, and at least one polymer, compound, and/or graftable substrate of the disclosure. In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is a cross-linking reagent. In some embodiments, the solution further comprises an alcohol. Any alcohol can be used, as understood by one of ordinary skill in the art. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the solution is an antibacterial solution. In some embodiments, the solution is a biocidal solution. In some embodiments, the solution is an antiviral solution. In some embodiments, the solution is an antifungal solution. In some embodiments, the solution is an antiprotozoal solution. In some embodiments, the solution is a ready-to-use solution for grafting. In some embodiments, the compound, polymer and/or graftable substrate is selected from formula (XVIIa), formula (XVIIIa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (III), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), optionally selected from any one of formula (XVII), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), or optionally any one of formula (I), formula (Ia), formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (II), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (XVa).

Methods of preparing a solution comprising an alcohol, at least one grafting enhancer and/or grafting adjuvant, and at least one polymer, compound, and/or graftable substrate of the disclosure are understood by one of ordinary skill in the art. In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is a cross-linking reagent. In some embodiments, the solution comprises an alcohol and at least one composition comprising at least one polymer, compound, and/or graftable substrate of the disclosure and at least one grafting enhancer and/or grafting adjuvant. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In a non-limiting example, the solution is prepared by adding the at least one grafting enhancer and/or grafting adjuvant to a solution comprising an alcohol and at least one polymer, compound, and/or graftable substrate of the disclosure. In some embodiments, the solution is stable after preparation and can be stored for a period of time after which the solution can be deposited on a surface in order to graft the polymer, compound, and/or graftable substrate of the disclosure onto the surface. In some embodiments, the solution comprising an alcohol, at least one grafting enhancer and/or grafting adjuvant, and at least one polymer, compound, and/or graftable substrate of the disclosure is stable for up to 1 day, up to 2 days, up to 3 days, up to 4 days, up to 5 days, up to 6 days, up to 7 days, up to 2 weeks, up to 3 weeks, up to 1 month, up to 2 months, up to 3 months, up to 4 months, up to 5 months, up to 6 months, up to 7 months, up to 8 months, up to 9 months, up to 10 months, up to 11 months, up to 1 year, or up to 2 years after preparation, or more. In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is added to a solution comprising an alcohol and at least one polymer, compound, and/or graftable substrate of the disclosure and deposited onto a surface without storing the solution prior to grafting.

In some embodiments, the composition and/or solution comprises the at least one polymer, compound, and/or graftable substrate of the disclosure in an amount of about 99.9% to about 50% (v/v), about 99.9% to about 60% (v/v), about 99.9% to about 70% (v/v), or about 99.5% to about 75% (v/v), and the at least one grafting enhancer and/or grafting adjuvant in an amount of about 0.1% to about 50% (v/v), about 0.1% to about 40% (v/v), about 0.1% to about 30% (v/v), or about 0.5% to about 25% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant. In some embodiments, the composition and/or solution comprises the at least one polymer, compound, and/or graftable substrate of the disclosure in an amount of about 99.9% (v/v), 99.8% (v/v), 99.7% (v/v), 99.6% (v/v), 99.5% (v/v), 99.4% (v/v), 99.3% (v/v), 99.2% (v/v), 99.1% (v/v), 99% (v/v), 98% (v/v), 97% (v/v), 96% (v/v), 95% (v/v), 94% (v/v), 93% (v/v), 92% (v/v), 91% (v/v), 90% (v/v), 85% (v/v), 80% (v/v), 75% (v/v), 70% (v/v), 65% (v/v), 60% (v/v), 55% (v/v), or 50% (v/v), and the at least one grafting enhancer and/or grafting adjuvant in an amount of about 0.1% (v/v), 0.2% (v/v), 0.3% (v/v), 0.4% (v/v), 0.5% (v/v), 0.6% (v/v), 0.7% (v/v), 0.8% (v/v), 0.9% (v/v), 1% (v/v), 2% (v/v), 3% (v/v), 4% (v/v), 5% (v/v), 6% (v/v), 7% (v/v), 8% (v/v), 9% (v/v), 10% (v/v), 15% (v/v), 20% (v/v), 25% (v/v), 30% (v/v), 35% (v/v), 40% (v/v), 45% (v/v), or 50% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant. In some embodiments, the grafting enhancer and/or grafting adjuvant is a cross-linking reagent.

In some embodiments, the composition and/or solution comprises the at least one polymer, compound, and/or graftable substrate of the disclosure and the at least one grafting enhancer and/or grafting adjuvant at a ratio between about 400:1 and about 1:1, between about 300:1 and about 2:1, or between about 200:1 and about 3:1. In some embodiments, the composition and/or solution comprises the at least one polymer, compound, and/or graftable substrate of the disclosure and the at least one grafting enhancer and/or grafting adjuvant at a ratio of about 400:1, about 350:1, about 300:1, about 250:1, about 200:1, about 150:1, about 100:1, about 50:1, about 40:1, about 30:1, about 20:1, about 10:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the grafting enhancer and/or grafting adjuvant is a cross-linking reagent.

In one aspect, the grafting enhancer and/or grafting adjuvant is phosphoric acid. In a non-limiting example, a metallic surface, for example a titanium surface, is treated with phosphoric acid prior to grafting the one or more compositions, polymers, graftable substrates, and/or compounds of the disclosure on the surface. In some embodiments, treating the surface of metal M with phosphoric acid provides M-O—P—OH layers, such as Ti—O—P—OH layers when the metal is titanium, which can increase the density of hydroxy groups at the surface of the metal and thus increase the grafting robustness. In some embodiments, the density of the hydroxy groups on a metal, such as but not limited to titanium, can be increased by treating the surface with phosphoric acid at temperature ranging from about 100° C. or greater, 110° C. or greater, 120° C. or greater, 130° C. or greater, or 140° C. or greater, in order to create a layer of M-O—P—OH (e.g. Ti—O—P—OH). In some embodiments, the compositions, polymers, graftable substrates, and/or compounds comprise one or more catechol moieties.

Surfaces

The disclosure provides in one aspect a surface grafted to a graftable substrate of the disclosure.

In one aspect of the disclosure, a compound of the disclosure is grafted onto a surface.

In some embodiments, the compound is a compound of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa). In some embodiments, the compound is a compound of any one of formula (Ib), formula (XV), formula (XVI), or formula (XVa). In some embodiments, the compound is a compound of any one of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa).

In one aspect of the disclosure, a polymer of the disclosure is grafted onto a surface. In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), formula (XVa), formula (XL), or formula (XLa). In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), or formula (XVa). In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), or formula (XLa).

When grafted, functional groups attached to the surface are covalently linked to moieties of the polymer or compound, such as catechol or silyl moieties. Grafting provides a stronger interaction between the surface and the polymer or compound than coating because in a coating, the interaction between the surface and the coated substrate is limited to electrostatic interactions rather than covalent linkages. Scheme 2 below shows an example of a polymer and compound of the disclosure grafted to a hydroxylated surface:

Any surface is contemplated by the disclosure, as understood by one of ordinary skill in the art. In a non-limiting example, the surface comprises a nanoparticle. Any nanoparticle is contemplated by the invention, as would be understood by one of ordinary skill in the art. In a non-limiting example, nanoparticles comprise any of Fe, Al, Cu, Zn, Mg, Mn, or other metal atoms. Non-limiting examples of surfaces include metals such as titanium and titanium alloys, iron, and steel; metal oxides; ceramics; polymers such as polyethylene (low and high reticulation for use in biomedical implants, after prior plasma activation), teflon (after prior plasma activation), polyethylene terephthalate (after prior plasma activation), and polypropylene (low and high density, after prior plasma activation), silicones, rubbers, latex, plastics, polyanhydrides, polyesters, polyorthoesters, polyamides, polyacrylonitrile, polyurethanes, polyethylene, polytetrafluoroethylene, polyethylenetetraphthalate and polyphazenes; paper; leather; textiles or textile materials such as cotton, jute, linen, hemp, wool, animals hair and silk, synthetic fabrics such as nylon and polyester; textile material includes fibers comprising fiber material such as acrylic polymers, acrylate polymers, aramid polymers, cellulosic materials, cotton, nylon, polyolefins, polyester, polyamide, polypropylene, rayon, wool, spandex, silk, and viscose; silicon; wood; glass; all cellulosic compounds; and gels and fluids not normally found within the human body. See, for example, US 2005/0249695, U.S. Pat. No. 8,475,782, US 2007/0292486, U.S. Pat. Nos. 4,282,366, 4,394,378, DE 2222997, DE 2229580, DE 2408192, GB 882067, all of which are incorporated by reference herein in their entireties.

In some embodiments, the surface comprises labile hydrogen atoms like thiols, amines or hydroxyl groups. In some embodiments, the surface comprises radical groups. In some embodiments, the surface comprises hydroxyl groups. In some embodiments, the surface is naturally hydroxylated. Examples of naturally hydroxylated surfaces include, but are not limited to, cotton, linen, leather, paper, cardboard, and wood. Some surfaces do not naturally contain such labile hydrogen atoms, and the labile hydrogen atoms have to be generated in situ, by using standard activation methods as would be understood by one of ordinary skill in the art. Non-limiting methods of activation include treatment with acid, oxidant treatment, plasma treatment, and UV/ozone treatment. Non-limiting examples of substances where hydroxylation occurred through activation include plastics, synthetic textiles, silicone, glass, and metals. In some embodiments, the surface is activated to produce hydroxyl groups. In some embodiments, the method of activation comprises treating a surface with piranha solution (piranha activation). In a non-limiting example, piranha activation includes immersing the substrate in a mixture of sulfuric acid and hydrogen peroxide (e.g. a 3:1 mixture of sulfuric acid and about 30% hydrogen peroxide) over a period of time ranging from about 1 minute to about 10 minutes, or about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 9 minutes, or about 10 minutes. In some embodiments, the ratio of sulfuric acid to hydrogen peroxide (e.g. 30% wt. hydrogen peroxide solution) ranges from about 1:1 to about 10:1, or about 1:1, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, or about 10:1.

In some embodiments, the cationic surface density of surfaces grafted with polymers and compounds disclosed herein is measured. The cationic surface density is a measurement of the charge density of quaternary ammonium compounds present on the surface, and a cationic surface density above a certain threshold indicates that bacterial death will occur quickly, as would be understood by one of ordinary skill in the art. In some embodiments, the cationic surface density is between about 10¹⁴/cm² and about 10²⁰/cm². In some embodiments, the cationic surface density is between about 10¹⁵/cm² and about 10¹⁷/cm². In some embodiments, the cationic surface density is greater than about 10¹⁵/cm².

In another aspect of the disclosure, the compounds, polymers, and/or graftable substrates of the disclosure can be used to change physical surface properties of materials. In a non-limiting example, compounds, polymers, and/or graftable substrates of the disclosure can modulate the hydrophilicity or hydrophobicity of a surface by varying the length of the lateral chain of the catechol or silane moiety. For example, alkyl chains more than four carbons in length (such as C₅-C₂₂ alkyl chains) can be added to the compounds and polymers of the disclosure, thereby increasing their hydrophobicity. In a non-limiting example, a compounds, polymers, and/or graftable substrates comprises quaternary nitrogens, wherein each quaternary nitrogen comprises either a moiety of the disclosure or a C₅-C₂₂ alkyl chain. After grafting, this increased hydrophobicity protects the grafted surfaces (such as wood, metals, plastics, textiles, and leather) by making them water-repellent to protect the surfaces from mold and mildew. In one embodiment, C₄-C₁₂ alkyl chains improve the biocidal properties of the compounds, polymers, and/or graftable substrates. In one embodiment, alkyl chains of C₁₃ or greater increase the hydrophobicity of the compounds, polymers, graftable substrates, and/or graftable composition

In one aspect of the disclosure, compounds of the disclosure can be covalently attached to polymers comprising COOH and/or NH₂ moieties through an amidation reaction. The resulting polymer can then be directly grafted to surfaces without employing complex multi-step reactions.

Applications

In one aspect, the graftable substrates, polymers, compounds, and compositions of the disclosure are useful for grafting onto surfaces used in various applications to contain and control the spread of infectious pathogens. Non-limiting examples of applications include:

• • a) Transportation (e.g. airline, automobile, train, ferry, subway, bicycles):
    • a. Automobile interiors (e.g. seats, screens, armrests, gearstick or selector)
    • b. Airline interiors (e.g. seats, armrests, meal trays, screens, curtains, bathrooms)
    • c. Train/subway interiors (e.g. seats, railings, bathrooms, waiting areas)
    • d. Bicycles (e.g. handlebars, seats)
    • e. Spaceship interiors, exploration robots, wastewater/urine filtration devices
    • f. High-touch surfaces in public spaces (e.g. doorknobs, handles, elevator buttons, handrails, plexiglass or glass windows, tables and trays, keyboards, computer mice, computer screens, remote controls, light switches, crosswalk buttons, parking buttons, chairs, pens)
  • b) Commerce:
    • a. Forms of Payment (e.g. bank bills, credit cards, bank checks)
    • b. Card readers, ATMs
    • c. Cash registers
    • d. Checkout conveyors
    • e. Paper or plastic consumer bags
  • c) Home:
    • a. Computers (e.g tablet screens, keyboards and their protective screens)
    • b. Doorknobs
    • c. Light switches
    • d. Water taps, sinks
    • e. Flooring surfaces: woods, laminate, marble
    • f. Carpets and rugs
    • g. Curtains, walls, ceiling
    • h. Toilets and toilet seats
    • i. HVAC (Heating, Ventilation and Air Conditioning) conduits
    • j. Kitchen surfaces
    • k. Appliances
    • l. Cutlery, glassware, porcelain items
    • m. Home furniture
    • n. Bedding
    • o. Draperies
    • p. Cushions
    • q. Leather, cotton, silk, and/or synthetic armchairs and couches
    • r. Book covers
    • s. Keys and keychains
    • t. Painted walls
  • d) Work Place:
    • a. Desks, tabletop surfaces
    • b. Phones
    • c. Notebooks
    • d. Pens
    • e. Speaker phones
    • f. Bathrooms
    • g. Lobby, elevator
  • e) Sporting equipment:
    • a. Sports gear and equipment
    • b. Yoga or fitness mats
    • c. Racket grips
    • d. Gym equipment
  • f) Petcare:
    • a. Fountains and bowls
    • b. Pet beds and baskets
    • c. Crates and kennels
  • g) Consumer products
    • a. Clothing (e.g. T shirts, pants, underwear, shirts, coats, caps (both cotton-based and/or synthetics)
    • b. Cell phones
    • c. Laundry detergents
    • d. Toys
    • e. Baby care: baby bottles, diapers, pacifiers
    • f. Scrubbing pads for cleaning surfaces for bathroom, kitchen, dishes, toilets
  • h) Beauty and Hygiene:
    • a. Oral care (e.g. toothbrushes)
    • b. Combs
    • c. Personal hygiene products (e.g. tampons, feminine pads, adult and baby diapers, period underwear)
    • d. Cosmetics
    • e. Jewelry (e.g. earrings, piercings)
    • f. Shaver blades and handles
    • g. Massage tables
    • h. Tattoo equipment
    • i. Saunas, bathtubs, spas, bidets
  • i) Public Spaces (e.g. in high-density communities):
    • a. Restaurants (e.g. tables, menus, screens, cutlery, glassware, porcelain and ceramic dishes, napkins, tablecloths)
    • b. Retail stores
    • c. Theatres (e.g. seats, armrests, bathrooms)
    • d. Airports (e.g. toilet surfaces, gate seating areas, community sharing stations, airplane ramp handrails)
    • e. Stadiums (e.g. seats, armrests, concession stands)
    • f. Government facilities (e.g. furniture and high-touch surfaces)
    • g. Public toilets (e.g. hand dryers, soap dispensers, standard and waterless urinals, urinal mats, toilet paper dispensers)
  • j) Construction
    • a. Wood-based products (e.g. decks, interiors, pillars)
    • b. Construction materials (e.g. lumber, metals, plastics, PVC, ceramics, paints)
    • c. Floor and roof tiles
    • d. Roofing products
    • e. Flooring
  • k) Industrial
    • a. PVC piping
    • b. Flooring
    • c. Paints
    • d. Filtration
  • l) Food applications
    • a. Food packaging
    • b. Water jugs and dispensers
  • m) Healthcare
    • a. Hospitals (e.g. bedding, draperies, cushions, bed rails, floors, walls, medical equipment (blood pressure cuffs, IV catheters and pumps, ventilators, urinals, oximetry)
    • b. Personal protective equipment (e.g. gowns, masks and respirators, gloves, jumpsuits, head covers)
    • c. Medical clinics equipment
    • d. Dentist office equipment
    • e. Veterinary office equipment (e.g. catching equipment, ultrasound machine, surgical tools)
    • f. Vision care (e.g. glasses, contact lenses)
    • g. Wound care (e.g. bandages, wound dressings)
    • h. Medical devices:
      • i. Implants (e.g. orthopedic and dental implants, vascular, urinary, and nerve catheters, vascular endoprostheses/prostheses, breast implants, bone cement, stents, surgical drains, surgical meshes, port-a-cath, extraventricular derivation drains, jejunostomy kits, gastric tubes, pacemakers, corneal implants, implantable defibrillators, spinal cord stimulators, custom 3D implants)
      • ii. External (e.g. thermometers, stethoscopes, dialysis machines, braces)
      • iii. Operating room equipment (e.g intubation kits, endoscopes, imaging equipment surfaces and their plastic covers, light handles, surgical drapes, bovie scratch pads, incision drape), surgical instruments, and consumables (e.g. needles, sutures, staples)
      • iv. Syringes and needles to prevent germ transmission in healthcare settings and to combat drug-abuse related infections (e.g. MRSA, HIV, HBV, HCV).
  • n) Defense:
    • a. Guns, weapons
    • b. Uniforms, boots
    • c. Marine applications (e.g. boat/submarine interiors and hulls, radars)
    • d. Satellites
    • e. Combat medical equipment

Grafting

In one aspect of the disclosure, methods for grafting graftable substrates of the disclosure are provided.

In one aspect of the disclosure, methods for grafting polymers are provided. In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), or formula (XVa).

In one aspect of the disclosure, methods for grafting polymers are provided. In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (Ie), formula (IIb), formula (VIa), formula (IXa), or formula (Ic). In some embodiments, the polymer is a polymer comprising at least one moiety of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa).

In one aspect of the disclosure, methods for grafting compounds are provided. In some embodiments, the compound is a compound of any one of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa). In some embodiments, the compound is a compound of any one of formula (Ib), formula (XV), formula (XVI), or formula (XVa). In some embodiments, the compound is a compound of any one of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa).

In one aspect of the disclosure, methods for grafting compounds are provided. In some embodiments, the compound is a compound of any one of formula (XV), formula (XVI), or formula (XVa).

In one aspect, the disclosure describes methods for grafting a substrate onto a surface. In some embodiments, the method includes depositing a graftable substrate of the disclosure onto the surface; and heating the surface for a period of time. In some embodiments, the graftable substrate is deposited by spraying, dip coating, or spin-coating. In some embodiments, the graftable substrate is deposited in a solvent comprising an alcohol selected from ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

In one aspect, the disclosure describes methods of grafting a polymer onto a surface, the method comprising depositing a polymer of the disclosure onto the surface; and heating the surface for a period of time. In some embodiments, the polymer is deposited in a solvent. In some embodiments, the solvent is an alcohol. In some embodiments, the solvent is water. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

In another aspect, the disclosure describes methods of grafting a compound onto a surface, the method comprising depositing a compound of the disclosure onto the surface; and heating the surface for a period of time. In some embodiments, the compound is deposited in a solvent. In some embodiments, the solvent is an alcohol. In some embodiments, the solvent is water. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

Any method of deposition is contemplated for use herein, as would be understood by one of ordinary skill in the art. Non-limiting examples of methods of deposition include spraying, dip coating, or spin-coating.

Any temperature suitable for grafting is contemplated for use herein, as would be understood by one of ordinary skill in the art. In some embodiments, the surface is heated to a temperature ranging from about 50° C. to about 120° C. In some embodiments, the surface is heated to a temperature of about 110° C.

As would be understood by one of ordinary skill in the art, any temperature suitable for grafting is contemplated for use herein. In some embodiments, the surface is heated for a period of time ranging from about 15 minutes to about 12 hours. In some embodiments, the surface is heated for a period of time ranging from about 6 hours to about 12 hours. In some embodiments, the surface is heated for a period of time ranging from about 15 minutes to about 90 minutes. In some embodiments, the surface is heated for a period of time ranging from about 30 minutes to about 60 minutes. In some embodiments, if the polymer or compounds to be grafted comprises a catechol moiety, the surface is heated for a period of time ranging from about 15 minutes to about 12 hours.

In some embodiments, the method further comprises washing the surface with a solvent. Non-limiting examples of solvents that can be used for washing include ether.

In some embodiments, the method further comprises sonicating the surface. Soncation can be performed for periods of time including, but not limited to, 5 minutes, 15 minutes, or 30 minutes. In some embodiments, the surface is sonicated while in a solvent. In non-limiting examples, solvents useful for sonication include acetone, ethanol, and distilled water.

In some embodiments, the surface is activated prior to grafting. Non-limiting examples of activation include plasma activation, acid activation, or UV/ozone activation.

Durable Coatings

In one aspect, the disclosure provides surface coatings comprising one or more polymers, substrates, and/or compounds of the disclosure having that are long-lasting, resistant to minor or moderate abrasion, and have durable self-cleaning properties.

In one aspect, the coatings are prepared by the sequential deposition of a sol-gel and a biocidal polymer solution. In some embodiments, the sol-gel comprises a mixture of an acid and a sol. In some embodiments, the biocidal polymer solution comprises one or more polymers, substrates, and/or compounds of the disclosure. In a non-limiting example, the sequential deposition of a titanium anatase sol-gel and an alcoholic biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure, such as a mixture of a random catechol copolymer such as catecholacetyl-coalkyl PVP and alkyl(4-catecholacetyl)dimethylammonium chloride, provides durable, long-lasting coatings that resisted immersion in various solvents, water, and abrasion.

In some embodiments, the sol-gel comprising the mixture of the acid and the sol is deposited first, followed by the biocidal polymer solution comprising one or more polymers, substrates, and/or compounds of the disclosure. In some embodiments, the biocidal polymers solution comprising one or more polymers, substrates, and/or compound of the disclosures is deposited first, followed by the sol-gel comprising the mixture of the acid and the sol. In some embodiments, the sol comprises a source of titanium oxide. In some embodiments, the sol-gel comprising the mixture of the acid and the sol comprises a mixture of peroxo-modified anatase sol and peroxo titanic acid. In some embodiments, the sol-gel comprising the mixture of the acid and the sol is an aqueous solution. In some embodiments, the sol-gel comprising the mixture of the acid and the sol is diluted in an aqueous solution. In some embodiments, the solution comprising one or more polymers, substrates, and/or compounds of the disclosure is an alcoholic solution. In some embodiments, the biocidal polymer solution comprising one or more polymers, substrates, and/or compounds of the disclosure comprises ethanol.

In one aspect, the disclosure provides a method of preparing a coating. In some embodiments, the method comprises depositing a sol-gel, and depositing a biocidal polymer solution. In some embodiments, the method comprises depositing a sol-gel on a surface, and depositing a biocidal polymer solution. In some embodiments, the method comprises depositing a biocidal polymer solution on a surface, and depositing a sol-gel. In some embodiments, the sol-gel is deposited first, followed by the biocidal polymer solution. In some embodiments, the sol-gel forms a first layer, and the biocidal polymer solution forms a second layer. In some embodiments, the biocidal polymer solution is deposted first, followed by the sol-gel. In some embodiments, the biocidal polymer solution forms a first layer, and the sol-gel forms a second layer. In some embodiments, the second layer is in contact with the first layer. In some embodiments the sol-gel comprises a mixture of an acid and a sol. In some embodiments the sol-gel comprises a mixture of an acid and a sol, and the biocidal coating solution compries one or more polymers, substrates, and/or compounds of the disclosure. In some embodiments, the acid is peroxo titanic acid. In some embodiments, the sol comprises a peroxo-modified anatase sol. In some embodiments, the sol-gel comprises a mixture of peroxo-modified anatase sol and peroxo titanic acid. In some embodiments, the sol-gel is an aqueous solution. In some embodiments, the sol-gel is diluted in an aqueous solution. In some embodiments, the biocidal polymer solution is an alcoholic solution. In some embodiments, the biocidal polymer solution comprises ethanol. In some embodiments, the first layer comprises metal oxide nanoparticles. In some embodiments, the first layer comprises titanium oxide nanoparticles. In some embodiments, the second layer comprises metal oxide nanoparticles. In some embodiments, the second layer comprises titanium oxide nanoparticles.

In one aspect, the disclosure provides a method of preparing a coating. In some embodiments, the method comprises depositing a first solution on a surface, and depositing a second solution. In some embodiments, the first solution forms a first layer, and the second solution forms a second layer. In some embodiments, the first solution and/or the second solution is a sol-gel. In some embodiments, the second layer is in contact with the first layer. In some embodiments the first solution comprises a sol-gel comprising a mixture of an acid and a sol, and the second solution comprises a biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure. In some embodiments the first solution comprises a biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure, and the second solution comprises a sol-gel comprising a mixture of an acid and a sol. In some embodiments, the sol-gel comprising the mixture of the acid and the sol comprises a mixture of peroxo-modified anatase sol and peroxo titanic acid. In some embodiments, the sol-gel comprising the mixture of the acid and the sol is an aqueous solution. In some embodiments, the sol-gel comprising the mixture of the acid and the sol is diluted in an aqueous solution. In some embodiments, the solution comprising one or more polymers, substrates, and/or compounds of the disclosure is an alcoholic solution. In some embodiments, the biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure comprises ethanol. In some embodiments, the first layer comprises metal oxide nanoparticles. In some embodiments, the first layer comprises titanium oxide nanoparticles. In some embodiments, the second layer comprises metal oxide nanoparticles. In some embodiments, the second layer comprises titanium oxide nanoparticles.

In some embodiments, the method comprises waiting a suitable period of time for the first solution to dry. In some embodiments, the method comprises waiting a suitable period of time for the second solution to dry. In some embodiments, the method comprises waiting a suitable period of time for the sol-gel to dry. In some embodiments, the method comprises waiting a suitable period of time for the biocidal polymer solution to dry. In some embodiments, a suitable period of time for the first solution and/or second solution and/or sol-gel and/or biocidal polymer solution to dry ranges from about 1 minute to about 12 hours, about 1 minute to about 15 minutes, about 5 minutes to about 10 minutes, about 6 hours to about 12 hours, or about 3 hours to about 6 hours. In some embodiments, the drying is performed at a temperature in a range from about 0° C. to about 250° C., about 25° C. to about 100° C., about 30° C. to about 75° C. or about 20° C. to about 30° C. In some embodiments, the drying is performed at room temperature, above room temperature, about 20° C., about 25° C., about 30° C., about 50° C., about 75° C., about 100° C., about 125° C., about 150° C., about 175° C., or about 200° C. In some embodiments, waiting a suitable period of time for the sol-gel and/or the sol-gel comprising the mixture of the acid and the sol to dry provides a plurality of metal oxide nanoparticles substantially in contact with a surface. In some embodiments, the metal oxide nanoparticles are titanium oxide nanoparticles. In some embodiments, the one or more polymers, substrates, and/or compounds of the disclosure are grafted onto the surface of one or more of metal oxide nanoparticles.

In one aspect, the disclosure provides a coating comprising metal oxide nanoparticles and one or more one or more polymers, substrates, and/or compounds of the disclosure. one or more one or more polymers, substrates, and/or compounds of the disclosure In one aspect, the disclosure provides a coating comprising metal oxide nanoparticles and one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and/or formula (XVa). In some embodiments, the coating comprises metal oxide nanoparticles and one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the coating comprises metal oxide nanoparticles and one or more compounds of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), formula (XLa).

In some embodiments, a plurality of metal oxide nanoparticles are substantially in contact with a surface. In some embodiments, the one or more one or more polymers, substrates, and/or compounds of the disclosure are grafted on the surface of one or more metal oxide nanoparticles.

In one aspect, the coating comprises a first layer in contact with a surface, and a second layer in contact with the first layer. In some embodiments, the first layer comprises metal oxide nanoparticles, and the second layer comprises one or more one or more polymers, substrates, and/or compounds of the disclosure. In some embodiments, the first layer comprises one or more one or more polymers, substrates, and/or compounds of the disclosure, and the second layer comprises metal oxide nanoparticles. In some embodiments, the metal oxide nanoparticles comprise titanium oxide nanoparticles. In some embodiments, the first layer comprises titanium oxide nanoparticles, and the second layer comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and/or formula (XVa). In some embodiments, the first layer comprises titanium oxide nanoparticles, and the second layer comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the first layer comprises titanium oxide nanoparticles, and the second layer comprises one or more compounds of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), formula (XLa). In some embodiments, the first layer comprises titanium oxide nanoparticles, and the second layer comprises a mixture of catecholacetyl-coalkyl-PVP and alkyl(4-catecholacetyl)dimethylammonium chloride.

In some embodiments, the coating comprises metal oxide nanoparticles. Non-limiting examples of metal oxide nanoparticles include titanium oxide, silicon oxide, zirconium oxide, zinc oxide, iron oxide, tungsten oxide, niobium oxide, lanthanum oxide, tin oxide, tantalum oxide, and one or more combinations thereof. In some embodiments, the metal oxide nanoparticles comprise titanium oxide nanoparticles.

In some embodiments, the coating comprising metal oxide nanoparticles is prepared using sol-gel application, as would be understood by one of ordinary skill in the art. In a non-limiting embodiment, a sol is combined with an aqueous solution of an acid to prepare a solution that can be deposited on a surface to provide a coating comprising metal oxide nanoparticles. In some embodiments, the sol comprises a source of metal oxide. Any source of metal oxide is contemplated by the present disclosure. Non-limiting examples of a source of metal oxide is anatase. In some embodiments, the anatase is peroxo-modified anatase. Any acid that can be combined with a source of metal oxide to prepare a sol is contemplated by the present disclosure. A non-limiting example of an acid is peroxo titanic acid. In some embodiments, the solution comprises a mixture of peroxo-modified anatase sol and peroxo titanic acid (titanium anatase). In some embodiments, the solution is an aqueous solution.

In some embodiments, the sol-gel comprises the acid and the sol comprising a source of metal oxide in a ratio of about 1:10 by weight/volume, about 1:5 by weight/volume, about 1:4 by weight/volume, about 1:3 by weight/volume, about 1:2 by weight/volume, about 1:1 by weight/volume, about 2:1 by weight/volume, about 3:1 by weight/volume, about 4:1 by weight/volume, about 5:1 by weight/volume, or about 10:1 by weight/volume.

In some embodiments, the sol-gel comprises a mixture of the sol and the acid in a range of about 0.1 wt % to about 2 wt %, about 0.5 wt % to about 1 wt %, or about 0.6 wt % to about 0.9 wt % by weight. In some embodiments, the sol-gel comprises a mixture of the sol and the acid of about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, about 0.4 wt %, about 0.5 wt %, about 0.6 wt %, about 0.7 wt %, about 0.8 wt %, about 0.9 wt %, about 1 wt %, 1.1 wt %, about 1.2 wt %, about 1.3 wt %, about 1.4 wt %, about 1.5 wt %, about 1.6 wt %, about 1.7 wt %, about 1.8 wt %, about 1.9 wt %, or about 20 wt %. In some embodiments, the sol-gel comprises a mixture of the sol and the acid of about 0.8 wt %. In some embodiments, the sol comprises a source of metal oxide. In some embodiments, the sol-gel comprises a mixture of peroxo-modified anatase sol and peroxo titanic acid (titanium anatase) of about 0.8% wt %. In some embodiments, the sol-gel is an aqueous solution.

In some embodiments, the coating of the disclosure comprises one or more of any polymers, substrates, and/or compounds of the disclosure. In some embodiments, the coating comprises a catechol moiety. In some embodiments, the durability of the coatings can be increased by the use of catechol moieties compared to other chemical moieties, while maintaining optimal efficiency. In a non-limiting example, mussel-inspired biomimetic strategies were developed in order to increase the bonding strength between coatings and surfaces by, for example, electrostatic interactions. The use of catecholamine was examined since catecholeamine is very sensitive to polymerization. In a non-limiting example, 4-chloroacetylcatechol and derivatives thereof were found to be useful as linkers to attach biocides to surfaces, either via electrostatic interactions or via covalent bonding. In some embodiments, the catechol moiety exhibited a more robust interaction with titanium nanoparticles compared with a silane moiety. Although not wishing to be bound by any particular theory, these results may be due to the Ti—O—C bond displaying a higher stability than the Ti—O—Si bond. In some embodiments, the combination of catechol moieties and titanium oxide nanoparticles was found to increase the durability of the biocidal coating. In some embodiments, the titanium nanoparticles of the coatings are able to interact with catechol moieties through Ti—O—C bonds. Also, most organosilanes are easily hydrolysable which makes their use difficult in wet or humid environments. In contrast, catechol-based compounds provide excellent adherence underwater.

In some embodiments, the coating comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the coating comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the coating comprises one or more compounds of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), and formula (XLa).

In some embodiments, the coating comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa) and metal oxide nanoparticles. In some embodiments, the coating comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa) and metal oxide nanoparticles. In some embodiments, the coating comprises one or more compounds of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), and formula (XLa) and metal oxide nanoparticles.

In some embodiments, the biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure is an alcohol solution. Any alcohol is contemplated by the disclosure. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the alcohol is ethanol. In some embodiments, the biocidal coating solution comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the biocidal coating solution comprises one or more compounds of formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In some embodiments, the biocidal coating solution comprises one or more compounds of formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), formula (XLa).

In some embodiments, the biocidal coating solution comprises a mixture of two or more polymers, substrates, and/or compounds of different structures. In some embodiments, the biocidal coating solution comprises two polymers, substrates, and/or compounds of different structures in a ratio of about 1:10 by weight/volume, about 1:5 by weight/volume, about 1:4 by weight/volume, about 1:3 by weight/volume, about 1:2 by weight/volume, about 1:1 by weight/volume, about 2:1 by weight/volume, about 3:1 by weight/volume, about 4:1 by weight/volume, about 5:1 by weight/volume, or about 10:1 by weight/volume. In some embodiments, the biocidal coating solution comprises two polymers, substrates, and/or compounds of different structures in a ratio of about 1:1 by weight/volume.

In some embodiments, the biocidal coating solution comprises one or more polymers, substrates, and/or compounds in a range of about 0.1 wt % to about 2 wt %, about 0.5 wt % to about 1 wt %, or about 0.6 wt % to about 0.9 wt % by weight. In some embodiments, the biocidal coating solution comprises one or more polymers, substrates, and/or compounds at about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, about 0.4 wt %, about 0.5 wt %, about 0.6 wt %, about 0.7 wt %, about 0.8 wt %, about 0.9 wt %, about 1 wt %, 1.1 wt %, about 1.2 wt %, about 1.3 wt %, about 1.4 wt %, about 1.5 wt %, about 1.6 wt %, about 1.7 wt %, about 1.8 wt %, about 1.9 wt %, or about 20 wt %. In some embodiments, the solution comprises one or more polymers, substrates, and/or compounds of different structures at about 1 wt %.

In one aspect, the disclosure provides a coating that is biocidal and hydrophobic, hydrophilic, and/or oleophobic. A non-limiting example of a method of preparing the coating is shown in FIG. 32.

In some embodiments, the coating comprises:

• • a) a siloxane-based polymer;
  • b) metal oxide nanoparticles;
  • c) an epoxy resin;
  • d) a biocidal moiety; and
  • e) one or more baking agents;wherein a plurality of the metal oxide nanoparticles are coated with a hydrophobic coating.

Any siloxane-based polymer is contemplated by the disclosure. Non-limiting examples of siloxane-based polymers include polydimethylsiloxane (PDMS), polyvinyl siloxane, hexamethyldisiloxane, hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, dodecamethylcyclohexasiloxane, decamethylcyclopentasiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, and tetradecamethylhexasiloxane. In some embodiments, the siloxane-based polymer is polydimethylsiloxane (PDMS).

In some embodiments, the coating comprises metal oxide nanoparticles. Non-limiting examples of metal oxide nanoparticles include titanium oxide, silicon oxide, zirconium oxide, zinc oxide, iron oxide, tungsten oxide, niobium oxide, lanthanum oxide, tin oxide, tantalum oxide, and one or more combinations thereof. In some embodiments, the metal oxide nanoparticles comprise titanium oxide nanoparticles. In some embodiments, a plurality of the metal oxide nanoparticles are substantially in contact with a surface.

In some embodiments, the hydrophobic coating comprises one or more hydrogenated and/or fluorinated alkyl chains, (hydrogenated n-alkyl chains between C₁₂ and C₂₂ or fluorinated n-alkyl chains between C₆ and C₁₂). In some embodiments, fluorinated n-alkyl the alkyl chain is C₁₂ or shorter, since alkyl chains longer than C₁₂ for fluorinated n-alkyl chains can exhibit poor solubility.

Any epoxy resin is contemplated by the disclosure. Non-limiting examples of epoxy resins include bisphenol A diglycidyl ether (DGEBA), diglycidyl ether bisphenol F (DGEBF), and Bisphenol E diglycidyl ether (DGEBE).

In one aspect, the biocidal moiety is one or more compounds selected from formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), formula (XXa), formula (I), formula (Ia), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), formula (IXa), formula (IXb), formula (IXb1), formula (IXc), formula (IXd), formula (IXe), formula (IXe1), formula (IXf), formula (IXg), formula (IXh), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXId), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XL), formula (XLa), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In one aspect, the biocidal moiety is one or more compounds selected from formula (Ib), formula (XV), formula (XVI), formula (XVa), formula (I), formula (Ia), formula (II), formula (IV), formula (V), formula (VI), formula (VIII), formula (IXa), formula (IXb), formula (IXc), formula (IXd), formula (IXe), formula (IXel), formula (IXf), formula (IXg), formula (IXh), formula (Ie), formula (IIb), formula (VIa), formula (IXaa), formula (Ic), and formula (XVa). In one aspect, the biocidal moiety is one or more compounds selected from formula (XVII), formula (XVIIa), formula (XVIIb), formula (XVIIc), formula (XVIII), formula (XIX), formula (XIXa), formula (XIXb), formula (XIXc), formula (XIXd), formula (XX), or formula (XXa), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XIa), formula (XIb), formula (XIc), formula (XVIIa), formula (XVIIIa), formula (XVIIb), formula (XVIIc), formula (XVIId), formula (XVIIe), formula (XVIIf), formula (XVIIg), formula (XVIIh), formula (XVIIj), formula (XXI), formula (XXIa), formula (XXIb), formula (XXII), formula (XXIIa), formula (XXIIb), formula (XXIIc), formula (XXId), formula (XL), formula (XLa). In some embodiments, the biocidal moiety is a metal the exhibits biocidal properties. Non-limiting examples of metals useful within the disclosure include silver and copper.

Any baking agent (e.g. curing agent) is contemplated by the disclosure. Non-limiting examples of baking and/or curing agents include aliphatic amines, polyamides, cycloaliphatic amines, aromatic amines, anhydrides, imidazoles, and Lewis acids.

In some embodiments, the siloxane-based polymer, metal oxide nanoparticles, epoxy resin, biocidal moiety, and one or more baking agents are combined and mixed to form a mixture. In some embodiments, the mixture applied to a surface. In some embodiments, a baking agent is added to and mixed with the siloxane-based polymer before being combined with the mixture. In some embodiments, a baking agent is added to and mixed with the epoxy resin before being combined with the mixture.

In some embodiments, after the mixture is applied to a surface, the mixture is baked. In some embodiments, the mixture is baked at a temperature of about 40° C. to about 80° C., or about 50° C. to about 70° C. In some embodiments, the mixture is baked at a temperature of about 40° C., about 45° C., about 50° C., about 55° C., about 60° C., about 65° C., about 70° C., about 75° C., or about 80° C.

In some embodiments, the mixture is baked for a suitable time period for the coating to harden. In some embodiments, the mixture is baked for about 1 h to about 5 h, or about 2 h to about 4 h. In some embodiments, the mixture is baked for about 1 h, about 2 h, about 3 h, about 4 h, or about 5 h.

The coatings may be applied to the surface using any method known in the art, as would be understood by one of ordinary skill in the art. In some embodiments, the coating is applied using an electrostatic sprayer. The use of electrostatic sprayers has the advantage of providing a homogeneous deposition of microdroplets onto targeted surfaces. Electrostatic sprayers have gained significant attraction during the COVID-19 pandemic, especially as useful tools for large sanitation of public areas such as stadiums, hospitals, airports, etc. In contrast to the durable and long-lasting coatings of the disclosure, most currently used compounds that are sprayed (hydrogen peroxide, chlorhexidine, long chain quaternary ammonium compounds) present only transient efficacy and durability. In some embodiments, the coating is applied using a dipping process.

The coatings described herein may be applied to any surface. Non-limiting examples of surfaces include metals such as cobalt, cobalt-chrome alloys, aluminum, titanium and titanium alloys, iron, steel and stainless steel; metal oxides; ceramics; polymers such as polyethylene, Teflon, polyethylene terephthalate, and polypropylene, silicones, rubbers, latex, plastics, polyanhydrides, polyesters, polyorthoesters, polyamides, polyacrylonitrile, polyurethanes, polytetrafluoroethylene, polyethylenetetraphthalate and polyphazenes, leather, textiles or textile materials, synthetic fabrics such as nylon and polyester; textile material comprising fibers comprising fiber material such as acrylic polymers, acrylate polymers, aramid polymers, nylon, polyolefins, polyester, polyamide, polypropylene, rayon, spandex, silk, viscose, silicon, and glass. In a non-limiting embodiment, the durability of the coatings was found to be particularly efficacious when the compositions and formulations were coated onto metallic substrates. In some embodiments, the surface is a metallic surface. In some embodiments, the surface is activated and/or naturally hydroxylated.

Conjugated Biomolecules

In one aspect, the disclosure provides biocidal moieties of the disclosure conjugated to biomolecules, which are optionally grafted to a surface.

In one aspect, the disclosure provides a compound of formula (XL):

wherein in formula (XL):

Z is a single bond or a linking group; and

B is a biomolecule.

In one aspect, the disclosure provides a compound of formula (XL):

wherein in formula (XL′):

Z is a single bond or a linking group; and

B is a biomolecule.

Any molecule with biological properties is contemplated by the present disclosure. In a non-limiting example, the biomolecule is a protein, enzyme, or peptide. In some embodiments, the biomolecules comprise a thiol group, such as a thiolated amino acid (e.g. cysteine). In some embodiments, the biomolecule comprises cysteine. In some embodiments, the biomolecule is cysteine. Non-limiting examples of biomolecules include bovine serum albumin, enzymes (oxidoreductases, transferases, hydrolases, lyases, ligases, and isomerases), polypeptides, antibodies, proteins including fluorescent proteins such as green fluorescent proteins (GFP), cerulean, mCherry, pericam, cameleons, pHluorins, EGFP (enhanced green fluorescent protein, clomeleon, halorhodopsins, channel rhodopsins, archaerhodopsins, mermaid, and GECI. In some embodiments, the the biomolecule is cysteine or bovine serum albumin.

In some embodiments, the biomolecule comprises one or more detectable moieties. In some embodiments, the detectable moiety is one or more selected from a fluorescent moiety, a phosphorescent moiety, and a luminescent moiety. In some embodiments, the detectable moiety is a fluorescent moiety selected from a coumarin moiety, a fluorescein moiety, a rhodamine moiety, an acridine moiety, an indole moiety, an isoindole moiety, an indolizine moiety, a quinoline moiety, an isoquinoline moiety, a chromene moiety, a xanthene moiety, anaphthalene moiety, a pyrene moiety, an a bimane moiety.

In one aspect, the disclosure provides a compound of formula (XLa):

wherein in formula (XLa):

Z is a single bond or a linking group; and

B is a biomolecule.

In one aspect, the disclosure provides a compound of formula (XLa′):

wherein in formula (XLa′):

Z is a single bond or a linking group; and

B is a biomolecule.

In some embodiments, Z is a single bond. In some embodiments, Z is a linking group. The linking group Z may be any organic moiety, as would be understood by one of ordinary skill in the art. In some embodiments, the linking group is selected from one or more linking groups selected from optionally substituted heterocyclyl, optionally substituted thiol, optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxy, —S—, and —O—. In some embodiments, the optionally substituted heterocycle is selected from optionally substituted triazole and optionally substituted succinimide. In some embodiments, the succinimide is a disuccinimide. In some embodiments, the succiminime is substituted with a thiol group.

In some embodiments, Z is selected from

In some embodiments, Z is selected from a single bond,

Any α, ω succinimide is contemplated by the present invention. Non-limiting examples of R include

wherein is an integer from 1 to 5. In some embodiments, R is

Non-limiting examples of methods for preparing compounds of formula (XL) and formula (XLa), including examples of formula (XL) and (XLa) grafted to a surface, are shown in FIG. 28-FIG. 31 and FIG. 49.

In some embodiments, a conjugated biomolecule of the disclosure can be prepared by grafting a catechol moiety onto a surface, and subsequently conjugating the biomolecule to the catechol moiety. In one aspect, the disclosure provdes a method of preparing a conjugated biomolecule, including but not limited to a compound of formula (XL), (XL′), (XLa), and/or (XLa′), the method comprising grafting a catechol moiety of formula (Ib) on to a surface, and reacting the compound of formula (Ib′) with a biomolecule of formula (XLb):

wherein in formula (Ib′):

X comprises a reactive group and/or a leaving group;

wherein in formula (XLb):

Z′ comprises a reactive group and/or a leaving group; and

B is a biomolecule.

In some embodiments, a conjugated biomolecule of the disclosure can be prepared by conjugating a biomolecule to a catechol moiety, and subsequently grafting the conjugated biomolecule to a surface. In one aspect, the disclosure provdes a method of preparing a conjugated biomolecule, including but not limited to a compound of formula (XL), (XL′), (XLa) and/or (XLa′), the method comprising reacting a catechol moiety of formula (Ib) with a biomolecule of formula (XLb), and grafting the resulting conjugated biomolecule onto a surface:

wherein in formula (Ib′):

X comprises a reactive group and/or a leaving group;

wherein in formula (XLb):

Z′ comprises a reactive group and/or a leaving group; and

B is a biomolecule.

In some embodiments, X comprises a reactive group and/or a leaving group selected from halo, —SH, —N₃,

wherein R is a linker. Any α, ω succinimide is contemplated by the present disclosure. Non-limiting examples of R include

wherein is an integer from 1 to 5,

wherein is an integer from 1 to 5, and

wherein is an integer from 1 to 5. In some embodiments, R is

In some embodiments, Z′ comprises a reactive group and/or a leaving group selected selected from halo, —SH, —N₃,

In some embodiments, the compounds of formula (XL) and/or formula (XLa) are grafted and/or applied onto surfaces to provide biocidal coatings that also comprise useful biomolecules. In some embodiments, the coatings are applied to biomedical applications such as medical devices, implants, contact lenses, catheters, and biosensors. In some embodiments, the coatings are useful as diagnostic agents.

In some embodiments, the disclosure relates to a compound used to prevent or facilitate the treatment of infections from or associated with medical implants. In some embodiments the compound comprises a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa), and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent. In some embodiments, the compound comprises a quaternized methylPEI, a propyltrimethoxysilane linker

a hexyl side chain, and a tetraethoxysilane cross linker.

In some embodiments, the PEI polymer is fully quaternized. In some embodiments, the molecular weight of the PEI polymer has a molecular weight in a range of about 160 kDa and about 750 kDa, or about 500 kDa to about 1000 kDa, or about 700 kDa to about 800 kDa. In some embodiments, the molecular weight of the PEI polymer has a molecular weight of about 160 kDa, about 170 kDa, about 180 kDa, about 190 kDa, about 200 kDa, about 210 kDa, about 220 kDa, about 230 kDa, about 240 kDa, about 250 kDa, about 260 kDa, about 270 kDa, about 280 kDa, about 290 kDa, about 300 kDa, about 310 kDa, about 320 kDa, about 330 kDa, about 340 kDa, about 350 kDa, about 360 kDa, about 370 kDa, about 380 kDa, about 390 kDa, about 400 kDa, about 410 kDa, about 420 kDa, about 430 kDa, about 440 kDa, about 450 kDa, about 460 kDa, about 470 kDa, about 480 kDa, about 490 kDa, about 400 kDa, about 510 kDa, about 520 kDa, about 530 kDa, about 540 kDa, about 550 kDa, about 560 kDa, about 570 kDa, about 580 kDa, about 590 kDa, about 600 kDa, about 610 kDa, about 620 kDa, about 630 kDa, about 640 kDa, about 650 kDa, about 660 kDa, about 670 kDa, about 680 kDa, about 690 kDa, about 700 kDa, about 710 kDa, about 720 kDa, about 730 kDa, about 740 kDa, or about 750 kDa.

In some embodiments, the hexyl side chain is present at 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% by weight in an alcohol.

In some embodiments, the cross-linking reagent is a silicate and/or a silane compound. Non-limiting examples of silicate compounds include tetramethylorthosilicate (tetramethoxysilane), trimethylmethoxyorthosilicate, trimethylethoxyorthosilicate, dimethyldimethoxyorthosilicate, dimethyldiethoxyorthosilicate, methyltrimethoxyorthosilicate, methyltriethoxyorthosilicate, tetramethoxyorthosilicate, tetraethoxyorthosilicate (tetraethoxysilane), methyldimethoxyorthosilicate, methyldiethoxyorthosilicate, dimethylethoxyorthosilicate, dimethylvinylmethoxyorthosilicate, dimethylvinylethoxyorthosilicate, tetraethylorthosilicate, methylvinyldimethoxyorthosilicate, methylvinyldiethoxyorthosilicate, diphenyldimethoxyorthosilicate, diphenyldiethoxyorthosilicate, phenyltrimethoxyorthosilicate, phenyltriethoxyorthosilicate, octadecyltrimethoxyorthosilicate, octadecyltriethoxyorthosilicate, 1,3-Disiloxanediol, 1,1,3,3-tetramethyl, 1,1,3,3-tetramethyldisiloxane-1,3-diol, 1,1,3,3-tetramethoxy-1,3-dimethyldisiloxane, tetraethoxy-1,3-dimethyldisiloxane, and 1,5-diethoxyhexamethyltrisiloxane. In some embodiments, the cross-linker is present at 10%, 15%, 20%, 25%, 30%, 35%, or 40% of the volume of the compound. In some embodiments, the cross-linking reagent is or comprises tetraethoxyorthosilicate (tetraethoxysilane, TEOS).

In some embodiments, the biocidal coating solution comprising one or more polymers, substrates, and/or compounds of the disclosure is an alcohol solution. Any alcohol is contemplated by the disclosure. Non-limiting examples of alcohols include ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the alcohol is ethanol.

In some embodiments, the biocidal coating solution comprises one or more polymers, and/or compounds of the disclosure in an amount of about 50% to about 99.9%; about 60% to about 99.9%; about 70% to about 99.9%, or about 70% to about 80%, or about 75% by weight based on the weight of the biocidal coating solution, and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% to about 50% (v/v), about 0.1% to about 40% (v/v), about 0.1% to about 30% (v/v), about 0.5% to about 25% (v/v), about 20% to about 30% (v/v), or about 25% (v/v) of the biocidal coating solution. In some embodiments, the biocidal coating solution comprises one or more alcohols, including but not limited to ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the alcohol is ethanol.

In some embodiments, the biocidal coating solution comprises a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa) in an amount of about 50% to about 99.9%; about 60% to about 99.9%; about 70% to about 99.9%, or about 70% to about 80%, or about 75% by weight based on the weight of the biocidal coating solution, and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% to about 50% (v/v), about 0.1% to about 40% (v/v), about 0.1% to about 30% (v/v), about 0.5% to about 25% (v/v), about 20% to about 30% (v/v), or about 25% (v/v) of the biocidal coating solution. In some embodiments, the biocidal coating solution comprises a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa) in an amount of or about 70% to about 80%, or about 75% by weight based on the weight of the biocidal coating solution, and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 20% to about 30% (v/v), or about 25% (v/v) of the biocidal coating solution. In some embodiments, the biocidal coating solution comprises one or more alcohols, including but not limited to ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol. In some embodiments, the alcohol is ethanol. In some embodiments, the at least one grafting enhancer and/or grafting adjuvant is or comprises a cross-linking reagent. In some embodiments, the cross-linking reagent is or comprises tetraethoxyorthosilicate (tetraethoxysilane, TEOS). In some embodiments, the the PEI polymer comprises at least one of the following moieties comprising a moiety of formula (XIa)

wherein each R² is independently optionally substituted alkyl.). In some embodiments, each moiety of formula (XIa)

In some embodiments, the molecular weight of the PEI polymer is of a range of about 700 kDa to about 800 kDa, or about 750 kDa.

Methods of Use

In one aspect of the disclosure, methods for controlling the growth of at least one bacteria, fungi, protozoa, or virus are provided. In some embodiments, the method comprising grafting a graftable substrate of the disclosure on a surface. In some embodiments, the method comprises grafting a compound of the disclosure onto a surface. In some embodiments, the method comprises grafting a polymer and/or compound of the disclosure onto a surface. In some embodiments, the surface is activated prior to grafting.

In some embodiments, the disclosure provides methods for controlling the growth of at least one bacteria, fungi, protozoa, or virus associated with and/or caused by implantation of a medical device in a subject in need thereof. In some embodiments, the medical device is an implant (e.g. orthopedic and dental implants, vascular, urinary, and nerve catheters, vascular endoprostheses/prostheses, breast implants, bone cement, stents, surgical drains, surgical meshes, port-a-cath, extraventricular derivation drains, jejunostomy kits, gastric tubes, pacemakers, corneal implants, implantable defibrillators, spinal cord stimulators, custom 3D implants). In some embodiments, the method comprising grafting a graftable substrate of the disclosure on a surface of the device. In some embodiments, the method comprises grafting a compound of the disclosure onto a surface of the device. In some embodiments, the method comprises grafting a polymer and/or compound of the disclosure onto a surface of a device. In some embodiments, the method comprises grafting a polymer and/or compound of the disclosure onto a surface of a device. In some embodiments, the surface is activated prior to grafting. In some embodiments, the bacteria are associated with a biofilm. In some embodiments, methods for controlling the growth of at least one bacteria, fungi, protozoa, or virus further comprise the absence of and/or reduction in one or more of fibrosis, inflammation, necrosis and/or neoangiogenesis compared to a medical device that does not comprise and/or is not grafted with a substrate, polymer, and/or compound of the disclosure. In some embodiments, the method further comprises preventing or treating surgical-site infections (SSIs), periprosthetic joint injections (PJIs), healthcare-acquired infections (HAIs), and/or implant-related infections (IRIs). In some embodiments, the method comprises preventing or treating infections associated with joint replacement, including but not limited to total knee replacement (TKR) and/or total hip replacement (THR).

In some embodiments, the bacteria is a gram-positive bacteria selected from M. tuberculosis (including multi drug resistant TB and extensively drug resistant TB), M bovis, M typhimurium, M bovis strain BCG, BCG substrains, M avium, M intracellulare, M africanum, M kansasii, M marinum, M ulcerans, M avium subspecies paratuberculosis, Staphylococcus aureus (including Methicillin-resistant Staphylococcus aureus (MRSA)), Staphylococcus epidermidis, Staphylococcus equi, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Listeria ivanovii, Bacillus anthraces, B. subtilis, Nocardia asteroides, and other Nocardia species, Streptococcus viridans group, Peptococcus species, Peptostreptococcus species, Actinomyces israelii and other Actinomyces species, Propionibacterium acnes, Clostridium tetani, Clostridium perfringens, Clostridium botulinum, other Clostridium species, and Enterococcus species.

In some embodiments, the bacteria is a gram-negative bacteria selected from Pseudomonas aeruginosa, other Pseudomonas species, Campylobacter species, Vibrio cholerae, Ehrlichia species, Actinobacillus pleuropneumoniae, Pasteurella haemolytica, Pasteurella multocida, other Pasteurella species, Legionella pneumophila, other Legionella species, Salmonella typhi, other Salmonella species, Shigella species, Brucella abortus, other Brucella species, Chlamydi trachomatis, Chlamydia psittaci, Coxiella burnetti, Escherichia coli, Neiserria meningitidis, Neiserria gonorrhea, Haemophilus influenzae, Haemophilus ducreyi, other Hemophilus species, Yersinia pestis, Yersinia enterolitica, other Yersinia species, Escherichia coli, Escherichia hirae, and other Escherichia species, as well as other Enterobacteriacae, Burkholderia cepacia, Burkholderia pseudomallei, Francisella tularensis, Bacteroides fragilis, Fusobascterium nucleatum, Provetella species, Cowdria ruminantium, Klebsiella species, and Proteus species.

In some embodiments, the virus is selected from avian influenza, human immunodeficiency virus, herpex simplex virus, human respiratory syncytial virus, Middle East respiratory syndrome-related coronavirus (MERS-CoV), rhinovirus, polio, rotavirus, measles, Ebola, West Nile, yellow fever, Dengue fever, lassa, lymphocytic choriomeningitis, Junin, Machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), parainfluenza, and Pichinde viruses.

In another aspect, the disclosure describes a method of preventing digestion of cellulose by an organism. In some embodiments, the method comprising grafting a polymer or a compound of the disclosure onto a surface comprising cellulose. In some embodiments, surface comprises wood cellulose. In some embodiments, the organism is selected from a wood boring gribble, a shipworm, a woodlice, and a wood-boring insect. Non-limiting examples of wood-boring insects include termites, bark beetles, horntail larvae, moth larvae, beetles. In some embodiments, the insect is a xylophage. Non-limiting examples of xylophages include termites, bark beetles, horntail larvae, moth larvae, and beetles.

EXAMPLES

The embodiments encompassed herein are now described with reference to the following examples. These examples are provided for the purpose of illustration only and the disclosure encompassed herein should in no way be construed as being limited to these examples, but rather should be construed to encompass any and all variations which become evident as a result of the teachings provided herein.

Example 1: Preparation of catechol moieties

4-(Iodoacetyl)catechol

4-(Chloroacetyl)catechol (100 mg) was treated with sodium iodide (100 mg) in acetone (30 mL) and heating to reflux for 3 hours to produce 4-(iodoacetyl)catechol. The reaction sequence is depicted in Scheme 3

4-(Azidoacetyl)catechol

4-(Chloroacetyl)catechol was treated with sodium azide in methanol and heated to reflux for 6 hours to produce 4-(azidoacetyl)catechol. The reaction was monitored through the intensity of the azido band at 2100 cm⁻¹. The reaction sequence is depicted in Scheme 4.

In a non-limiting example, 4-(azidoacetyl)catechol is linked to an alkyne using click chemistry to produce, respectively, triazole or tetrazole linkages, as would be understood by one of ordinary skill in the art. Scheme 5 illustrates examples of linkages formed using click chemistry.

4-(Aminoacetyl)catechol

4-(Azidoacetyl)catechol was treated with triphenylphospine in water to produce 4-(aminoacetyl)catechol. The reaction sequence is depicted in Scheme 6:

In a non-limiting example, 4-(aminooacetyl)catechol is linked to a carbonyl to form an amide, as would be understood by one of ordinary skill in the art. Scheme 7 illustrates an example of an amide linkage.

4-(cyanoacetyl)catechol

4-(Chloroacetyl)catechol was treated with potassium cyanide in dimethylformamide (DMF) to produce 4-(cyanoacetyl)catechol. The reaction sequence is depicted in Scheme 8:

In a non-limiting example, 4-(cyanoacetyl)catechol is linked to an alkyne using click chemistry to produce a tetrazole linkage, as would be understood by one of ordinary skill in the art. Scheme 9 illustrates an example of a tetrazole linkage.

3-(3,4-dihydroxybenzoyl) propionic acid

4-(Chloroacetyl)catechol was first treated with potassium cyanide in dimetylformamide (DMF) to form 4-(cyanoacetyl)catechol, followed by treatment with water to produce 3-(3,4-dihydroxybenzoyl) propionic acid. The reaction sequence is depicted in Scheme 10:

In a non-limiting example, 3-(3,4-dihydroxybenzoyl) propionic acid can be linked to an amine to form an amide, as would be understood by one of ordinary skill in the art. Scheme 11 illustrates an example of an amide linkage.

4-(Dimethylaminoacetyl)catechol

4-(Iodoacetyl)catechol was treated with dimethylamine and potassium carbonate in tetrahydrofuran in the presence of potassium carbonate to produce 4-(dimethylaminoacetyl)catechol. The reaction sequence is depicted in Scheme 12A:

Example 2: One-Pot Synthesis of Graftable Antibacterial Moieties

Surface grafting to confer antibacterial properties to high-touch surfaces can be achieved by the quaternization of long chain tertiary amines with halo-alkyl triethoxy or trimethoxysilanes. Even if this synthetic route provides a high yield of quaternary ammonium compounds, a small amount of volatile silane (<1%) still remains. This amount of silyl contaminant is potent enough to render spraying the quaternary ammonium compounds hazardous because of the particularly volatile properties of the silane compound. Reticulation in volume can cause serious damage to the eyes during the spraying procedure. Therefore, another process to graft these compositions on certain surfaces using a 4-haloacetylcatechol moiety was developed. In some embodiments, the 4-haloacetylcatechol moiety is treated with a dialkylaminoalkane in an alcohol (such as methanol and/or ethanol) and heated to reflux for 24 h. The general reaction sequence is depicted in Scheme 13A:

In Scheme 13A above, each R⁵ is independently optionally substituted alkyl; X is Cl, Br, or I, and n is an integer from 3 to 21.

This method of preparation does not result in the formation of byproducts. The 4-haloacetylcatechol moiety product is soluble in alcohols such as ethanol/methanol and in water, and it is ready to graft on a variety of surfaces, including hydroxylated surfaces (hydroxylation can be naturally-occuring on the surface or achieved by activation). When this moiety is deposited using methods such as spraying methods, the 4-haloacetylcatechol moiety does not present the same risks as the volatile silanes because the 4-haloacetylcatechol moiety is generally a solid at ambient temperature.

Scheme 13B below describes an alternative approach to preparing a quaternary ammonium catechol compound using 4-(dimethylaminoacetyl)catechol. 4-(dimethylaminoacetyl)catechol is treated with an alkyl halide (in a non-limiting example, the alkyl halide comprises a C₁₆-C₂₀ alkyl chain) to provide a quaternary 4-(alkyldimethylaminoacetyl)catechol compound.

Example 3: Synthesis of a Ready-to-Graft Catechol-Based Quaternary Ammonium Moieties

1 gram of N, N dimethyloctadecylamine 89% (Mw: 297.57 g/mol; 1 eq) was reacted with 620 mg of 4-chloroacetylcatechol (Mw: 186.59 g/mol; 1 eq) in boiling isopropyl alcohol for 24 hours to obtain the product octadecyl(4-catecholacetyl)dimethylammonium chloride (ODMcat) (90% yield). FIG. 14 shows the IR spectrum of octadecyl(4-catecholacetyl)dimethylammonium chloride compared to 4-chloroacetylcatechol. The reaction sequence is depicted in Scheme 14:

Example 4: Grafting on Filter Paper

Depositing and Grafting:

A 1 cm² piece of filter paper was impregnated with a solution of ODMcat in isopropanol and baked in an oven at 110° C. for one hour. Subsequently the sample was rinsed with ethanol and sonicated in the same solvent for 20 min in order to eliminate excess reagent.

Visual Fluorescein Test

Samples of the impregnated filter paper were transferred to a 1% fluorescein solution for 10 minutes. Subsequently, the samples were thoroughly washed with distilled water and sonicated in distilled water until there was no additional release of physisorbed fluorescein from the samples in order to remove excess physisorbed fluorescein from the samples. The samples were then air dried. The sample treated with ODMcat appeared markedly orange, whereas the control sample (untreated filter paper) appeared white (FIG. 1). The orange color is due to the retained fluorescein dye molecules bound to covalently attached quaternary amino groups from the ODMcat moieties.

Example 5: Grafting on Cotton

Depositing and Grafting

Cotton was soaked in an alcoholic solution of ODMcat. Cotton samples were baked at 110° C. for one hour. Control cotton was soaked in distilled water. The samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent. The samples were then sonicated for 10 minutes in distilled water, and then rinsed with distilled water.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4. FIG. 2 shows images of control and ODMcat-treated cotton after vortexing, sonication and drying. The orange appearance of ODMcat-treated cotton is due to the extremely high number of counter ion of the fluorescein dye bound to the quaternary amino groups of the ODMcat moiety, which is covalently attached to the cotton.

Example 6: Grafting on Glass

Glass Preparation and Activation

4.84 cm² glass coverslips (22 mm×22 mm) were sonicated in acetone, ethanol, and distilled water. The coverslips were then placed in a piranha solution [96% sulfuric acid/30% hydrogen peroxide (2/1, v/v)] for 10 minutes to create Si—OH groups on the glass surface. All coverslips were subsequently rinsed with distilled water, sonicated in distilled water and air dried.

Depositing and Grafting

The solution prepared according to Example 3 was deposited on the activated glass coverslips by spin-coating. Samples were subsequently baked at 110° C. for 60 minutes. Samples were then retrieved and sonicated in ethanol for 5 minutes for adequate removal of any remaining physisorbed reagent. Samples were then sonicated for 5 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated using UV/Vis absorbance of fluorescein. Fluorescein dye molecules (negatively charged) strongly bind to quaternary amino groups (positively charged) belonging to the polymeric chain. The stoichiometry of fluorescein binding is estimated at one dye molecule per four quaternary ammonium moieties. Treated plates were placed in a 1% fluorescein aqueous solution for five minutes, and then rinsed and sonicated in distilled water for several minutes in order to remove physisorbed fluorescein. Plates were rinsed with distilled water and immersed in 3 mL of CTAB 0.5% (aqueous solution of cetyltrimehylammonium bromide) along with PBS (Phosphate-Buffered Saline) (90% CTAB/10% PBS) and sonicated for 10 minutes. The optical density of chemisorbed fluorescein was measured at 501 nm wavelength.

Surface cationic density was estimated according to the following formula:

$\frac{A\times V\times \mathrm{NA}}{\epsilon \times S}$

A: absorbance of fluorescein solution at 501 nmV: volume (3 mL)N_A: Avogadro's number (6.022140857×10²³ mol⁻¹)ε: fluorescein molar absorptivity or molar extinction coefficient (L×mol⁻¹×cm⁻¹).S: surface in cm²

Measurements were as follows:

Spin-coated treated glass slides (150 μL deposit, 4000 RPM, 40 seconds, 3 mL CTAB/PBS)

$A=0.021\pm 0.003$

Calculated surface cationic density: 4×10¹⁴ cations/cm²

These results confirmed the effective grafting of the catechol-based quaternary ammonium moiety on glass.

Example 7: One-Pot Synthesis of Graftable Biocidal Polymers

General Synthesis for Polymer Based on Poly(4-Vinylpyridine)

Poly(4-vinylpyridine) (PVP; Mw 60,000 g/mol; 1 eq.) was reacted with 4-(chloroacetyl)catechol (also known as 2-chloro-3,4-dihydroxyacetophenone) or 4-(iodoacetyl)catechol (0.1 to 0.5 eq) and an alkyl chain (for example, a C₄ to C₁₂ carbon chain) in an alcoholic solvent to prepare a random copolymer having biocidal properties. The solution was refluxed overnight. Subsequently, a C₄ to C₁₂ alkyl-halide (excess) was added (to check the best length for optimal biocidal activity. The reaction was stopped anytime between 24 hours and 4 days depending on the desired

$\frac{N+}{N}$

quaternization ratio. Partial quaternization resulted in a polymer displaying both biocompatibility and biocidal activity. Maximum yield of quaternarization results in a polymer displaying high biocidal activity. As depicted in Scheme 15, 1 equivalent of PVP is used to prepare a random copolymer that comprises a molar ratio of A to B of x:(1-x), wherein 0.1≤x≤0.5.

Example 8: Synthesis of Random Copolymer (C1)

In a one-pot process, a random copolymer was prepared by reacting iodopropyltrimethoxysilane (0.05 eq.), polyvinylpyridine (PVP) (1 eq.) and bromobutane (1 eq.) in boiling methanol for a reaction time of four days.

Example 9: Synthesis of a Novel Random Copolymer: Catecholacetyl-Cobutyl PVP (C2)

In a one-pot process, a solution comprising a random copolymer was prepared by reacting 4-chloroacetylcatechol (0.06 eq.), polyvinylpyridine (PVP) (1 eq.) and bromobutane (1 eq.) in boiling ethanol for a reaction time of four days. Scheme 16 depicts the general synthetic scheme. The molar ratio of A to B in the random copolymer is 0.06:0.94. The IR spectrum of catecholacetyl-cobutyl PVP is shown in FIG. 15. FIG. 18 illustrates an IR spectrum of the catecholacetyl-cobutyl PVP co-polymer (C2) with non-quaternized PVP in the background. FIG. 19 illustrates an IR spectrum of the catecholacetyl-cobutyl PVP co-polymer (C2). The PVP-catechol-codecyl-PVP co-polymer was also prepared using similar methods, demonstrating successful modification of the lateral alkyl chain. FIG. 20 illustrates an IR spectrum of the catecholacetyl-codecyl PVP co-polymer with commercial non-quaternized PVP in the background.

Example 10: Polymer Grafting on Titanium Surfaces

Plate Preparation and Activation

1 cm² titanium plates (99.6% purity, Goodfellow, Cambridge Ltd., Huntington, United Kingdom) were successively polished on 3 grains (P800, P2000 and P4000 grit paper) for 1 minute, 2 minutes, and 3 minutes, respectively. After exhaustive washings and a 5-minute sonication process with ethanol in order to remove residual particles, the plates were placed in a piranha solution [96% sulfuric acid/30% hydrogen peroxide (2/1, v/v)] for two minutes to activate the surfaces. All plates were subsequently rinsed, sonicated in distilled water and air dried.

Deposition and Grafting

The solution of random copolymers prepared according to Example 9 (C2) was deposited by either by spin-coating or dip coating on activated plates. The plates were then baked overnight at 110° C. The plates were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Plates were then sonicated for 10 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated by a fluorescein test as described above in Example 6. According to Kügler et al., the charge-density threshold for optimum efficiency of biocidal cationic surfaces is ≈10¹⁵ cations/cm².

The following measurements were made:

Titanium plates (1 cm²) were spin-coated with an aqueous solution of 5% C₂ and baked at 110° C. overnight (150 μL deposit, 4000 RPM, 40 seconds). The surface cation density calculation was based on the use of 3 mL CTAB/PBS solution:

$A=0.079\pm 0.005$

• • Calculated surface cationic density: 7.44×10¹⁵ cations/cm²

Titanium plates (1 cm²) were dip-coated with an aqueous solution of 5% C₂ and baked at 110° C. overnight. Calculation was based on the use of 3 mL CTAB/PBS solution.

$A=0.139\pm 0.009$

• • Calculated surface cationic density: 1.31×10¹⁶ cations/cm²

Whether C2 was spin-coated or dip-coated on titanium, it systematically displayed a high cationic charge density above the threshold for optimum efficiency (biocidal activity).

Example 11: Grafting on Cotton

Deposition and Grafting

A solution of random copolymer as prepared according to Example 9 (C2) was used to soak cotton for 5 minutes. Control cotton was soaked in distilled water. Treated and control cotton were baked at 110° C. for 60 minutes. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Samples were then sonicated for 10 minutes in distilled water, and rinsed with distilled water.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4. FIG. 3 shows images of the control and C2-treated cotton after vortexing. FIG. 4 shows images of the control and C2-treated cotton after vortexing, sonication and drying. The orange appearance of C2-treated cotton is due to the high number of counterions of the fluorescein dye bound to the quaternary amino groups of the C2 moiety, which is covalently attached to the cotton.

Example 12: Grafting on Filter Paper

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of aqueous 5% C2 (synthesized according to Example 9) and baked at 110° C. for 60 minutes. A control filter paper sample was impregnated with distilled water. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Samples were then sonicated for 10 minutes in distilled water, and rinsed with distilled water.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4.

FIG. 5 illustrates images of the control and C2-treated filter paper after fluorescein test. The orange appearance of C2-treated filter paper is due to the high number of fluorescein dye molecules bound to the quaternary amino groups of the C2 moiety, which is covalently attached to the cotton.

Example 13: Grafting on Aluminum

Plate Preparation and Activation

4 cm² and 1 cm² aluminum 1060 plates were respectively sonicated in acetone, ethanol, and in distilled water. The plates were immersed in an NaOH 0.1M solution for 20 minutes to remove the protective layer of aluminum oxide to provide Al—OH bonds. All plates were subsequently rinsed, sonicated in distilled water for 10 min, and air dried.

Deposition and Grafting

Solutions of random copolymers as prepared according to Example 8 (C1) and Example 9 (C2) were deposited by either spin-coating, dip-coating, or immersion on activated plates. The plates were baked at 110° C. overnight. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Samples were then sonicated for 10 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated with a fluorescein test as described in Example 6. According to Kügler et al., the charge-density threshold for optimum efficiency of biocidal cationic surfaces is ≈10¹⁵ cations/cm²

The following measurements were made:

Aluminum plates (4 cm²) were immersed and placed in an aqueous solution of 5% C₂ (3 mL) and baked at 110° C. for 3 hours

• • Calculated Surface cationic density: 4.44×10¹⁶ cations/cm²

5% C₂ dip-coated aluminum plates (4 cm²) were baked at 110° C. for 3 hours.

Calculated Surface cationic density: 1.4×10¹⁶ cations/cm²

Aluminum plates (4 cm²) were immersed in a solution of C1 as prepared in Example 8 and baked at 110° C. for 3 hours. Calculated Surface cationic density: 1.04×10¹⁵ cations/cm²

These results demonstrate that C2 has a higher surface cationic density than C1, and thus exhibits improved properties over C1.

Due to the high affinity of the catechol group with metals, using these catechol linker provides a very efficient moiety for grafting surface metals such as titanium, aluminum, stainless steel, etc.

Example 14: Grafting of Glass

Glass Preparation and Activation

Glass slides were prepared according to Example 6.

Deposition and Grafting

A solution of random copolymer was prepared according to Example 9 (C2) was deposited by immersion on activated glass. After deposition, samples were baked at 110° C. for 60 minutes. Samples were then sonicated in ethanol (10 minutes) and water (10 minutes).

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated as previously described.

The following measurements were made:

• • Glass slides (10.5 cm²) were immersed in an aqueous solution of 5% C2 as prepared in Example 9 and baked at 110° C. for 60 minutes.
  • Calculated Surface cationic density: 7.6×10¹⁵ cations/cm²

Example 15: Grafting on Balsa Wood

Sample preparation

1 cm² squares of balsa wood (1.5 mm thick) were sonicated in acetone, ethanol and distilled water. All squares were then air dried.

Deposition and Grafting

The samples were placed in a mixture of 5% C2 solution (as prepared in Example 9) in ethanol/water v/v (4 mL) for 30 min. After deposition, samples were baked at 110° C. for 60 minutes. Samples were then sonicated in ethanol (10 minutes) and water (10 minutes).

Surface Charge Determination by Fluorescein Test

Volumetric cationic concentration (N⁺/cm³) was calculated by a fluorescein test as described above.

The following measurements were made:

Balsa wood samples were immersed in a mixture of 5% C2 solution (prepared as described in Example 9) in ethanol/water v/v (4 mL) and baked at 110° C. for 1 hour.

Volumetric cationic concentration: 1.32x x10¹⁷ cations/cm³

Example 16: Grafting on Stainless Steel

Stainless Steel Preparation and Activation

4 cm² stainless steel plates were sonicated in acetone, ethanol, and distilled water. They were then placed in a sulfochromic acid solution for 20 minutes at 50° C. to create hydroxy groups on the surface. All stainless steel plates were subsequently rinsed, sonicated in distilled water for 10 minutes, and air dried.

Deposition and Grafting

A solution of random copolymer prepared according to Example 9 (C2) was deposited by immersion on activated stainless steel plates. The plates were baked at 110° C. overnight. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Samples were then sonicated in ethanol (10 minutes) and water (10 minutes).

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated as previously described.

The following measurements were made:

Stainless steel samples (4 cm²) were immersed in an aqueous solution of 5% C2 (prepared as described in Example 9) and baked at 110° C. overnight.Calculated Surface cationic density: 6.75×10¹⁵ cations/cm²

Example 17: General Synthesis for Preparation of a Graftable Polymer from Poly(Vinylbenzyl Chloride)

A graftable polymer is prepared from poly(vinylbenzyl chloride) (FIG. 6). Polyvinylbenzylchloride (MW 55000 g/mol; 1 eq.; mixture of meta and para) is dissolved in THE (tetrahydrofuran). 4-(Dimethylaminoacetyl)catechol is added to the reaction mixture (between 0.05 and 0.20 equivalents). The reaction mixture is heated at reflux for four hours. An excess of a C₄-C₁₂ alkyldimethylamine in a solution of ethanol is added to the reaction mixture, which is heated at reflux for 24 hours, and then cooled down to room temperature. The volume of the reaction mixture is reduced by two-thirds using rotary evaporation, and subsequently cooled down to about 4-8° C. A non-solvent of polycations, such as ether or acetone, is added until the appearance of a precipitate. After cooling the mixture at 4° C. overnight, the precipitate is isolated by vacuum filtration, washed with a non-solvent (ex: ether) and dried under vacuum to provide the desired catechol quaternized polymer. Scheme 17 depicts the general synthesis of the resulting random copolymer that comprises a molar ratio of A to B of x:(1-x), wherein 0.05≤x≤0.5.

Treating polyvinylbenzylchloride with the dimethylaminoacetylcatechol results in the partial quaternization of polyvinylbenzylchloride. Subsequently, the addition of an excess of the dimethylaminoalkyl chain quaternizes the remaining available sites (unreacted monomer units).

Example 18: Preparation of a Graftable Polymer from Poly(Vinylbenzyl Chloride)

A graftable polymer is prepared from poly(vinylbenzyl chloride) using the method of Example 17. 4-(Dimethylaminoacetyl)catechol (0.1 eq) and N,N-dimethyldecan-1-amine (excess) are used. The polymer product is a random copolymer (polyvinylbenzyl(N-catecholacetyl-N,N-dialkyl)ammonium bromide) comprising a molar ratio of quaternized nitrogen with a catechol moiety (A in Scheme 17) to quaternized amine with a butyl moiety (B in Scheme 17, where the alkyl chain is 4 carbons) of 0.1:0.9.

Example 19: General synthesis for preparation of a graftable polymer from polyethylenimine (PEI)

A graftable polymer was prepared from polyethylenimine (PEI) (FIG. 7). PEI contains 53 monomer units, each containing 11 nitrogens (N) that can be quaternized.

PEI (MW 750,000 g/mol) was treated with a mixture of formaldehyde and formic acid to exhaustively methylate primary and secondary amine groups as depicted below in Scheme 18.

It was surprisingly found that PEI with low molecular weight (such as 25,000 g/mol) leads to surfaces exhibiting low cationic charge densities (under 10¹⁵ charges/cm²). FIG. 8 illustrates the structure of PEI after exhaustive methylation. FIG. 23 illustrates IR spectra of methylated hyperbranched PEI (750 kDa) and commercial PEI (750 kDa).

The reaction mixture was neutralized with concentrated aqueous KOH, and then the extracted three times with chloroform. The organic layer was dried over sodium sulphate and evaporated to dryness.

The methylated PEI product was then dissolved in alcohol (preferentially ethanol; other possibilities include isopropyl alcohol, t-butyl alcohol, or t-amyl alcohol) and treated with 4-(chloroacetyl)catechol or 4-(iodoacetyl)catechol (0.2-0.5 eq.). The reaction mixture was heated at reflux for several hours. A solution of a C₄-C₁₂ alkyl halide (excess) dissolved in alcohol was added to the reaction mixture, which was then heated at reflux for 2 to 4 days. The reaction mixture was cooled down to about 4-8° C., and the volume of the reaction mixture was reduced to about one third of its initial volume using rotary evaporation. A non-solvent was added until the appearance of a precipitate, and then the reaction mixture was kept at 4° C. overnight. The precipitate was then isolated by vacuum filtration, washed with a non-solvent (ex: ether) and dried under vacuum to provide the desired catechol quaternized PEI polymer. Scheme 19 depicts an example of a fully methylated PEI monomer linked to a catechol moiety.

Example 20: Preparation of a Graftable Polymer from Polyethylenimine (PEI)

A graftable polymer was prepared from PEI using the method of Example 19. 4-(chloroacetyl)catechol (0.1 eq) and 1-bromodecane (excess) were used. The polymer product was a random PEI copolymer comprising a molar ratio of quaternized nitrogen with a catechol moiety to quaternized nitrogen with a decyl moiety of 0.1:0.9. In some embodiments, 1-bromohexane is used in place of 1-bromodecane. The corresponding PEI polymer with a hexyl moiety instead of a decyl moiety was also prepared. FIG. 22 illustrates an IR spectrum of fully methylated quaternized PEI random copolymer partially grafted with acetylcatechol group and decyl group in ratio 1/9.

Example 21: General Synthesis for Preparation of a Graftable Polymer from Polyethylenimine (PEI) with an Alkylsilane Moiety

A graftable polymer was prepared from polyethylenimine (PEI) and an alkylsilane moiety, such as 3-iodopropyltrimethoxysilane, using the same procedure described in Example 19, except the alkylsilane (0.05 eq.) is used instead of the 4-(chloroacetyl)catechol or 4-(iodoacetyl)catechol. A side chain was also added (bromohexane). The solution was refluxed for 96 hours. Scheme 20 depicts an example of a fully methylated PEI monomer linked to a 3-propyltrimethoxysilane moiety.

Example 22: Preparation of a Graftable Polymer from Polyethylenimine (PEI)

A graftable polymer was prepared from PEI using the method of Example 21. 3-iodopropylmethoxysilane (0.1 eq) was used as the alkylsilane, and 1-bromohexane (excess) was used as the C₄-C₁₂ alkyl halide. The polymer product was a random PEI copolymer comprising a molar ratio of quaternized nitrogen with alkylsilane moiety to quaternized nitrogen with a hexyl group of 0.1:0.9. Partially silanized PEI could not be isolated because of the eventual reticulation of the silane linker in the absence of solvent. In a non-limiting example, the quaternized methylated PEI is kept in an alcoholic or alcoholic/water solution. FIG. 34 shows an IR spectrum fully methylated quaternized PEI random copolymer partially grafted with propyltrimethoxysilane group and hexyl group in ratio 1/9. The fully methylated quaternized PEI random copolymer partially grafted with propyltrimethoxysilane group and hexyl group in ratio 1/9 was also prepared using similar methods, indicating successful modification of the side alkyl chain. A fully methylated quaternized PEI random copolymer partially grafted with propyltrimethoxysilane group and decyl group was also prepared.

Example 23: General Method of Deposition and Grafting of Ready-to-Use Biocidal Polymers

Polymers disclosed herein are grafted onto a variety of hydroxylated surfaces. The surface may be naturally hydroxylated or is artificially activated prior to deposition by methods including oxidant treatment with plasma, acid or UV/ozone. The hydroxylated surface is positioned for deposition. The polymer is deposited onto the surface using methods such as spraying, dip coating, or spin-coating. The polymer is grafted to the surface by heating, for example by heating the surfact to 110° C. for 30 to 60 min. In some embodiments, overnight curing by heat may be preferred for metals such as stainless steel or titanium. The temperature may be adjusted if a different temperature is desired. When grafting at a temperature lower than 110° C., a longer heating period is then utilized. After completion, the substrate is washed (with an alcohol such as isopropanol) to eliminate physisorbed polymers and retain only covalently grafted polymers. Optionally, the substrate may be sonicated. After washing, the substrate is dried under air atmosphere.

Example 24: General Preparation of Dipodal Silane Compounds

Example 24 describes the preparation of novel dipodal silane compounds and moieties, which can be covalently grafted onto a variety of surfaces. Various dipodal silane compounds are further substituted with an alkyl chain by treatment with an alkyl halide in a single step reaction to provide highly hydrophobic/hydrophilic compounds that are ready-to graft on a variety of surfaces, including hydroxylated or activated surfaces, with the benefit of being much more stable and extremely resistant to hydrolysis compared to conventional silanes. In an non-limiting example, a dipodal silyl amine compound is treated with an alkyl halide, such as a C4-C22 alkyl halide, in an alcohol such as isopropanol, and heated to reflux for 24-96 hours.

Example 25: Preparation of bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium compounds

N,N′-Bis[3-(trimethoxysilyl)propyl]ethylenediamine (1 eq.) was treated with an alkyl halide (2 eq.), such as a C₁₈-C₂₂ alkyl bromide, in isopropanol and heated at reflux for 96 h to produce bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium compounds. An exemplary reaction scheme is depicted in FIG. 9. The spectrum is provided in FIG. 33.

Example 26: General Preparation of Quaternized Dipodal Silane Compounds

A compound prepared by Example 24 is quaternized by treatment with at least 1 equivalent of an alkyl halide, such as a C₄-C₂₂ alkyl halide, in an alcohol, such as isopropanol, heated to reflux for 24-96 h. These quaternary ammonium compound exhibit antimicrobial properties, and provide same advantage of using dipodal silanes as described in Example 24.

Example 27: Preparation of bis(3-trimethoxysilylpropyl)-N,N-methyloleylammonium bromide

Bis(3-trimethoxysilylpropyl)-N-methylamine (1 eq.) is treated with an alkyl halide (1 eq.), such as a C₁₈-C₂₂ alkyl bromide, in isopropanol and heated at reflux for 48 h to produce bis(3-trimethoxysilylpropyl)-N,N-methylalkyllammonium bromide. An exemplary reaction scheme is depicted in FIG. 10. The advantage of grafting such a dipodal quaternary ammonium compound is to confer superior robustness to the grafted film thanks to an improved reticulation within the film. The resulting compound resists hydrolysis significantly better than monopodal-silane quaternary ammonium compounds.

Example 28: Preparation of quaternized bis(3-trimethoxysilylpropyl)dialkylammonium bromide

Bis(3-trimethoxysilylpropyl)amine (1 eq.) was treated with an alkyl halide (2 eq.), such as a C₁₈-C₂₂ alkyl bromide, in isopropanol and heated at reflux for 96 h to produce bis(3-trimethoxysilylpropyl)-N,N-dialkylammonium bromide. An exemplary reaction scheme is depicted in FIG. 11A and FIG. 11B. FIG. 17 illustrates an IR spectrum of bis(3-trimethoxysilyl)propyl-N,N-dioctadecyl ammonium bromide. Bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide can also be prepared using similar methods using bromohexadecane instead of bromooctadecane.

Example 29: Preparation of a Random Dipodal Polyvinylpyridine (PVP) Copolymer

Bis(3-trimethoxysilylpropyl)-N-methylamine was treated with 1,4-bis(bromomethyl)benzene (0.05 eq. to 0.2 eq., for example 0.05 eq.) in ethyl acetate stirred at reflux for 48 h to produce a quaternary amine compound, which was then treated with PVP in isopropanol and stirred at reflux for 12 h. FIG. 25 shows an IR spectrum of the quaternary amine compound named bis(3-trimethoxysilypropyl)-N-bromoacetylamine, which is a linker for PVP. The polymer was then treated with at least 1 equivalent of an alkyl halide, such as a C₄-C₂₂ alkyl halide, in an alcohol (for example, isopropanol), to provide a random PVP copolymer substituted with a molar ratio of the bis(3-trimethoxysilylpropyl)-N-methyl-N-para-xylyl moiety to the alkyl group moiety of about (0.05≤x≤0.2)(1-x). FIG. 26 shows an IR spectrum of the dipodal quaternized PVP with a C₄ lateral chain (red line) compared to the intermediate bis(3-trimethoxysilypropyl)-N-bromoacetylamine (blue line). In some embodiments, when 0.05 eq of bis(3-trimethoxysilypropyl)-N-bromoacetylamine is used, the molar ratio is about 0.05:0.95. FIG. 12A and FIG. 12B illustrate exemplary reaction schemes for linking a bis(3-trimethoxysilylpropyl)-N-methyl-N-para-xylyl moiety to a polymer comprising a monomer comprising a tertiary amine to form a quaternary amine. Non-limiting examples of polymers that comprise tertiary amines include polyvinylpyridine (PVP and polyethylenimine (PEI). The quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-codecyl-PVP co-polymer was also prepared using similar methods but replacing bromobutane by bromodecane, indicating successful modification of the side alkyl chain. FIG. 24 illustrates an IR spectrum of dipodal quaternized PVP with a C₄ lateral chain (quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-para-xylyl-cobutyl-PVP).

Example 30: Preparation of a Random Poly(Vinylbenzyl Chloride) Copolymer

Bis(3-trimethoxysilylpropyl)-N-methylamine (0.05 eq. to 0.2 eq., for example 0.05 eq.) was treated with poly(vinylbenzyl chloride) (1 eq.) in isopropanol and stirred at reflux for 6 h. The polymer was then treated with at least 1 equivalent of a C₄-C₁₂ alkyldimethylamine in an alcohol (for example, isopropanol) and stirred at reflux for 24 h to provide a random poly(vinylbenzyl chloride) copolymer substituted with a molar ratio of the bis(3-trimethoxysilylpropyl)-N-methylamine moiety to the C4-C12 alkyldimethylamine moiety was about (0.05≤x≤0.2)(1-x). In some embodiments, when 0.05 eq of bis(3-trimethoxysilylpropyl)-N-methylamine is used, the molar ratio is about 0.05:0.95. An exemplary reaction scheme is depicted in FIG. 13. The IR spectrum of the PVBC copolymer is shown in FIG. 16. FIG. 27 shows an IR spectrum of the dipodal quaternized PVBC polymer with a C₁₀ lateral chain (blue line) compared to bis(3-trimethoxysilypropyl)-N-bromoacetylamine (black line). FIG. 21 illustrates an IR spectrum of the poly(vinylbenzyl chloride) co-polymer partially quaternized with bis(N-methyl)3 propyltrimethoxysilane groups and N,N-dimethylbutyl groups.

Example 31: Electrostatic Spraying of a Biocidal Polymer Coupled with Titanium Anatase

The preparation of catechol-coalkyl-PVP was described in U.S. Pat. No. 10,743,539, which is incorporated by reference herein in its entirety. The structure of catecholacetyl-coalkyl PVP is shown in Scheme 21.

The preparation of octadecyl(4-catecholacetyl)dimethylammonium chloride is described in Example 3 above (see also Scheme 22)

An ethanolic solution containing 1% random copolymer catecholacetyl-coalkyl-PVP bearing catechol groups and alkyl groups with a 1:10 ratio and 1% weight/weight of octadecyl(4-catecholacetyl)dimethylammonium chloride is prepared. In this Example, the mixture of these two compounds (catecholacetyl-coalkyl-PVP and octadecyl(4-catecholacetyl)dimethylammonium chloride) is referred to as biocidal polymer coating solution.

A 0.8% titanium anatase phase in aqueous solution (an equal mixture of peroxotitanium acid and peroxo-modified anatase sol) was prepared according to Ichinose et al., Journal of Sol-Gel Science and Technology 22:33-40 (2001), which is incorporated by reference herein in its entirety.

A glass slide was treated according to the following protocol:

• • 1) The surface was prepared by cleaning with isopropanol, and allowed to dry;
  • 2) The sprayer was held about 1 m from the target surface.
  • 3) The titanium anatase phase in aqueous solution (a mixture of peroxotitanic acid and peroxo-modified anatase sol 0.8%) was sprayed onto the surface using an electrostatic sprayer to form a coating on the target surface.
  • 4) The surface was allowed to dry for 5 to 10 minutes.
  • 5) The electrostatic sprayer was rinsed with distilled water.
  • 6) The biocidal polymer coating solution was added to the sprayer tank.
  • 7) The biocidal polymer coating solution was sprayed onto the surface at a 1 m distance away from the surface.
  • 8) The surface was examined to ensure it was not over-saturated with coating solution.
  • 9) The surface was allowed to dry for several hours.

In non-limiting embodiments, the surface substrate is dried at room temperature for 5 to 10 minutes and electrostatically sprayed with the second solution. In non-limiting embodiments, the sample can be cured overnight at room temperature or cured in an oven at 90° C. for 30 min to increase the stability of the coating through the interaction of titanium and the catechol moiety.

A second glass slide was treated according to the protocol described above, except the surface was coated with the biocidal polymer solution first, followed by the titanium anatase phase.

In both methods, it was observed that the coating resisted repeated manual friction (over 20 cycles) using both wetted and dry paper towel, cotton-based cloth, and polyester/polypropylene wipes.

Visual Fluorescein Test

Treated and control glass slides were transferred to a 1% fluorescein solution for 10 minutes. Subsequently, the samples were thoroughly washed with distilled water until there was no additional release of physisorbed fluorescein from the samples. The samples were then air dried. Orange color was observed on the surfaces due to the retained fluorescein dye molecules bound to quaternary amino groups from both catecholacetyl-coalkyl PVP and octadecyl(4-catecholacetyl)dimethylammonium chloride.

The fluorescein test showed that treated surfaces retained their orange color before and after manual friction, which means that the coating resisted moderate abrasion. These results were observed on the slide where the biocidal polymer coating solution was sprayed after the titanium anatase solution, but not on the slide where the biocidal polymer coating solution was sprayed before the titanium anatase solution. While not wishing to be bound by theory, this result may be due to the underlying PVP with cationic charges being shielded from fluorescein due to the anatase layer.

In order to examine whether silane-based compounds would also be useful in these coatings, an ethanolic solution of 1% octadecyldimethyl(3-trimethoxysilylpropyl)ammonium chloride was prepared as a spray-on coating as well as a mixture of peroxotitanic acid and peroxo-modified anatase sol 0.8%. Each solution was electrostatically sprayed onto glass slides sequentially with the titanium anatase sprayed first followed by the solution comprising the octadecyldimethyl(3-trimethoxysilylpropyl)ammonium chloride, and the slides were cured overnight at room temperature according the protocol described above.

It was observed that the silane-based coating did not resist manual friction using wetted paper towel, cotton-based cloth, and polyester/polypropylene wipes. The entire coating was easily removed from the glass slide after only three cycles, indicating a lack of durability and robustness of the layer. Although not wishing to be bound by theory, this result suggests that the covalent bonding between catechol moieties and titanium nanoparticles is superior to the silanization displayed by organosilanes.

The fluorescein test showed that after extensive washing of the glass slides with water, the fluorescein was completely removed from the surfaces that underwent three cycles of manual friction, indicating that the coating comprising the silane-based compound did not resist minor abrasion and that the quaternary ammonium compound was removed from the surface.

Example 32: Grafting on Filter Paper of Acetylcatechol-Co-Hexyl-PEI

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of aqueous 1% acetylcatechol-co-hexyl-PEI (synthesized according to Example 20 with a hexyl moiety instead of a decyl moiety) and grafted according to Example 4.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4. The orange appearance of acetylcatechol-co-hexyl-PEI-treated filter paper is due to the high number of fluorescein dye molecules bound to the quaternary amino groups of the acetylcatechol-co-hexyl-PEI, which is covalently attached to the cotton.

Example 33: Grafting on glass of acetylcatechol-co-hexyl-PEI

Glass Preparation and Activation

Glass slides were prepared according to Example 6.

Depositing and Grafting

The solution prepared according to Example 20 was deposited on the activated glass coverslips by spin-coating. Samples were subsequently baked at 110° C. for 60 minutes. Samples were then retrieved and sonicated in ethanol for 5 minutes for adequate removal of any remaining physisorbed reagent. Samples were then sonicated for 5 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Measurements were as follows:

Spin-coated treated glass slide (150 L deposit, 4000 RPM, 40 seconds, 3 mL CTAB/PBS)Calculated surface cationic density using 750 kDa PEI as a reagent: 2.1±0.4×10¹⁶ cations/cm² Calculated surface cationic density using 25 kDa PEI as a reagent: 3.4±0.2 x10¹⁴ cations/cm²

These results confirmed the effective grafting of the catechol-based quaternary ammonium moiety on glass.

Example 34: Grafting on Filter Paper of Random 3-Trimethoxypropylsilyl-Cohexyl-methylatedPEI

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of aqueous 1% with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI (synthesized according to Example 21 and grafted according to Example 4.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4. The orange appearance of 3-trimethoxypropylsilyl-cohexyl-methylatedPEI treated filter paper is due to the high number of fluorescein dye molecules bound to the quaternary amino groups of the 3-trimethoxypropylsilyl-cohexyl-methylatedPEI, which is covalently grafted to the cotton.

Example 35: Grafting on glass of random 3-trimethoxypropylsilyl-cohexyl-methylatedPEI

Glass Preparation and Activation

Glass preparation was performed according to Example 6.

Depositing and Grafting

The solution prepared according to Example 21 was deposited on the activated glass coverslips by spin-coating. Samples were subsequently baked at 110° C. for 60 minutes. Samples were then retrieved and sonicated in ethanol for 5 minutes for adequate removal of any remaining physisorbed reagent. Samples were then sonicated for 5 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N+/cm2) was calculated by a fluorescein test as described in Example 6.

Measurements were as follows:

Spin-coated treated glass slide (150 L deposit, 4000 RPM, 40 seconds, 3 mL CTAB/PBS)Calculated surface cationic density using 750 kDa PEI as a reagent: 3.6±0.3×10¹⁶ cations/cm² Calculated surface cationic density using 25 kDa PEI as a reagent: 4.2±0.4 x10¹⁴ cations/cm²

These results confirmed the effective grafting of the silane-based quaternized methyl PEI on glass.

Example 36: Grafting on filter paper of quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-para-xylyl-cobutyl-PVP

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of aqueous 1% quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP (synthesized according to Example 29) and grafted according to Example 4.

Visual Fluorescein Test

Samples were treated according to the visual fluorescein test described in Example 4. The orange appearance of quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP treated filter paper is due to the high number of fluorescein dye molecules bound to the quaternary amino groups of the quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP, which is covalently attached to the cotton.

Example 37: Grafting on glass of quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP

Glass Preparation and Activation

Glass preparation was performed according to Example 6.

Depositing and Grafting

The solution prepared according to Example 29 was deposited on the activated glass coverslips by spin-coating, and then covalently grafted on the activated glass according to Example 6.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated by a fluorescein test as described in Example 6.

Measurements were as follows:

Spin-coated treated glass slide (150 μL deposit, 4000 RPM, 40 seconds, 3 mL CTAB PBS)

Calculated surface cationic density: 9.3±0.5×10¹⁵ cations/cm²

These results confirmed the effective grafting of the dipodal silane-based polycations on glass.

Example 38: Grafting on glass of bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide

Glass Preparation and Activation

Glass preparation was performed according to Example 6.

Depositing and Grafting

The solution prepared according to Example 28 (bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide) was deposited on the activated glass coverslips by spin-coating. Samples were subsequently baked at 110° C. for 60 minutes. Samples were then retrieved and sonicated in ethanol for 5 minutes for adequate removal of any remaining physisorbed reagent. Samples were then sonicated for 5 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N+/cm2) was calculated by a fluorescein test as described in Example 6.

Measurements were as follows:

Spin-coated treated glass slide (150 L deposit, 4000 RPM, 40 seconds, 3 mL CTAB/PBS)

Calculated surface cationic density: 2.7±0.2×10¹⁴ cations/cm²

These results confirmed the effective grafting of the dipodal silane-based quaternary ammonium alkyl chain on glass.

Example 39: Grafting of L-cysteine on filter paper using 4-iodoacetylcatechol as a linker

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of acetonic 4-iodoacetylcatechol (Synthesized according to Example 1, Scheme 3 and after filtration of the NaCl product) and baked at 110° C. for 60 minutes. A control filter paper sample was impregnated with distilled water. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent and air-dried. The filter paper sample was immersed in a 10× Phosphate Buffer Saline (PBS) containing 500 mg of L-cysteine. The solution was stirred overnight at room temperature and protected from light. The filter paper sample was removed from the solution and sonicated for 10 minutes in deionized water. It was then impregnated with a 1% aqueous ninhydrin solution and heated at 90° C. for 10 minutes.

The treated filter paper appeared purple after ninhydrin dye was applied and the control paper remained white after ninhydrin dye application (FIG. 35). This result indicates the presence of grafted L-cysteine on the filter paper.

Example 40: Grafting of L-cysteine on glass using 4-iodoacetylcatechol as a linker

Glass Preparation and Activation

Glass preparation was performed according to Example 6.

Depositing and Grafting

The activated glass was immersed in the solution prepared according to Example 1, Scheme 3 and after filtration of the NaCl product. Immersed samples were transferred to an oven at 110° C. for 60 minutes. Samples were then retrieved and sonicated in ethanol for 5 minutes for adequate removal of any remaining physisorbed reagent. Samples were then air-dried. The glass slide was immersed in a 10× Phosphate Buffer Saline (PBS) containing 500 mg of L-cysteine. The solution was stirred overnight at room temperature. The glass slide was removed from the solution and sonicated for 10 minutes in deionized water. It was then covered by a 1% aqueous ninhydrin solution and heated at 90° C. for 10 minutes. Purple-blue spots appeared on the surface which proves the presence of grafted L-cysteine on the glass surface. As a comparative tool, a control glass slide was sonicated in ethanol for 10 minutes and air-dried. The glass slide was covered with 1% aqueous ninhydrin solution and heated at 90° C. for 10 minutes. No spots appeared on the surface of the control glass slide.

These results confirmed the effective grafting of an amino-acid such as L-cysteine using a iodocatechol linker.

Example 41: Grafting Examples

FIG. 37-FIG. 44 illustrate successful grafting of polymers and compounds of the disclosure onto filter paper. FIG. 37 illustrates a comparison between control filter paper and treated filter paper with quaternized bis(3-trimethoxysilylpropyl)-N-methyl-N-paraxylyl-cobutyl-PVP. FIG. 38 illustrates a comparison between control filter paper and treated filter paper with poly(vinylbenzyl chloride) partially quaternized with bis(N-methyl)₃-propyltrimethoxysilane groups and N,N-dimethylbutyl groups. FIG. 39 illustrates a comparison between control filter paper and treated filter paper with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI (from PEI at 750 kDa). FIG. 40 illustrates a comparison between control filter paper and treated filter paper with 3-trimethoxypropylsilyl-codecyl-PEI (from PEI at 25 kDa). FIG. 41 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilypropyl)-N-bromoacetylamine. FIG. 42 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilyl)propyl-N,N-dihexadecyl ammonium bromide. FIG. 43 illustrates a comparison between control filter paper and treated filter paper with bis(3-trimethoxysilylpropyl)-N,N-methylalkylammonium bromide. FIG. 44 illustrates a comparison between control filter paper and treated filter paper with bis[3-(trimethoxysilyl)propyl-N,N′-tetraalkylethylenediammonium.

Example 42: Grafting of L-cysteine on filter paper using 4-azidoacetylcatechol as a linker through a click reaction

A non-limiting example of a grafting of a biomolecule comprising a propargyl group is shown in this Example, which describes the grafting of propargylcysteine. Scheme 23 shows a non-limiting example of a grafted structure.

Synthesis of Propargylcysteine

L-cysteine (3 g) was dissolved in 4 mL of an aqueous ammonium hydroxide solution (30%) along with 20 mL of DI water. The flask was immersed in an ice bath at approximately 0° C. 5 g of a propargyl bromide solution (80% in toluene) was slowly added drop-wise to the cysteine solution. After one hour, the precipitate was isolated, washed with a PBS solution, acetone, and air-dried to produce a solid product. ATR spectroscopy revealed the presence of the alkyne group v C≡C and v C—H respectively at 3320 cm⁻¹ and 2970 cm⁻¹.

Grafting of 4-azidoacetylcatechol

A 1 cm² dry filter paper sample was impregnated with 4 drops of 4-azidoacetylcatechol (Synthesized according to Example 1, Scheme 4) and baked at 110° C. for 60 minutes. ATR spectroscopy revealed the presence of the azido group in the final product by the appearance of the stretching band of azido at 2116 cm⁻¹. A control filter paper sample was impregnated with distilled water. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent and air-dried.

Click Reaction:

For the click reactions, the following solution was prepared: DMF (15 mL)+CuSO₄ (5%), sodium ascorbate (10%), and 1 mmol propargylcysteine. The filter paper grafted with 4-azidoacetylcatechol was immersed in the previous solution which was heated in the dark at 60° C. for 6 hours. The filter paper was removed, rinsed with distilled water, ethanol, and air-dried. The filter paper was positive to the ninhydrin test indicating that the aminoacid was grafted on the filter paper compared with control.

Example 43: Grafting of bovine serum albumin (BSA) on filter paper using 4-iodoacetylcatechol as a linker

Deposition and Grafting

A 1 cm² dry filter paper sample was impregnated with 4 drops of acetonic 4-iodoacetylcatechol (Synthesized according to Example 1, Scheme 3 and after filtration of the NaCl product) and baked at 110° C. for 60 minutes. A control filter paper sample was impregnated with distilled water. Samples were then sonicated in ethanol for 10 minutes to remove any excess of reagent and air-dried. The filter paper sample was immersed in a borate buffer containing bovine serum albumin (BSA) 1%. The solution was stirred overnight at room temperature and protected from light. The filter paper sample was removed from the solution and sonicated for 10 minutes in deionized water. It was then impregnated with a 1% aqueous ninhydrin solution and heated at 90° C. for 10 minutes.

The treated filter paper appeared slightly purple after the ninhydrin dye was applied. The control paper remained white after ninhydrin dye application. This result indicated the presence of grafted BSA on the filter paper. In order to sensitize this test, treated filter paper grafted with BSA according to the same protocol was immersed in a 1% dansyl chloride solution in acetone along with dimethylaminopyridin. After rinsing in acetone and water, and drying, the filter paper exhibited a fluorescent aspect under UV light (365 nm), indicating the presence of amino groups of BSA, unlike the control filter paper which appeared blue under the same UV light.

Example 44: Use of Tetraethoxysilane (TEOS) as a Cross-Linking Reagent to Maximize the Number of Grafting Sites and Improve the Grafting Robustness by Cross-Linking

After the synthesis of random 3-trimethoxypropylsilyl-cohexyl-methylatedPEI it was found that adding pure TEOS (at 0.5% to 25% of the total volume of alcoholic polymer and TEOS) to the alcoholic polymer solution significantly improved the robustness of the grafted layer.

Stainless Steel Plate Preparation and Activation

1 cm² stainless steel plates were sonicated in ethanol, air dried, and air-plasma activated.

Deposition and Grafting

An ethanolic solution of random copolymers prepared according to Example 21 with 25% TEOS (3-trimethoxypropylsilyl-cohexyl-methylatedPEI/TEOS, 3:1, v/v) was deposited by dip coating on three activated plates. The plates were then baked overnight at 130° C. for optimal cross-linking. The plates were then sonicated in ethanol for 10 minutes to remove any excess of reagent. Plates were then sonicated for 10 minutes in distilled water, and rinsed with distilled water.

Surface Charge Determination by Fluorescein Test

3-trimethoxypropylsilyl-cohexyl-methylatedPEI/TEOS stainless steel plates: Surface cationic density (N⁺/cm²) 7.2±4×10¹⁶ cations/cm²

Serial Autoclaving

3-trimethoxypropylsilyl-cohexyl-methylatedPEI/TEOS-grafted stainless steel plates were sequentially autoclaved, (20 psi, 121° C. for 30 minutes followed by a 20 min drying cycle) and underwent a fluorescein test before and after each autoclave cycle in order to determine the grafting robustness. FIG. 45 represents a chart displaying the relationship between the number of autoclaving cycles and sample cationic charge densities. While the charge density initially varied between samples and significantly decreased between the first and 5^th cycles, it was found that after 5 cycles, the charge density remained constant (6^th through 9^th), above the density threshold for biocidal activity.

Sequential Washing Machine Cycles

Forty 2″×2″ 100% pure cotton white fabric coupons were sonicated in ethanol and air dried. Coupons were impregnated with an ethanolic mixture of 1% TEOS and either 1% C1 (as prepared in Example 8, 20 coupons) or 1% 3-trimethoxypropylsilyl-cohexyl-methylatedPEI (20 coupons) and dried in a clothes dryer for 10 minutes to covalently graft the textile. Coupons were then washed in a washing machine (normal load selected, “colors” setting) using an excess of commercial detergent (enzyme-based), and dried in the same clothes dryer for 30 minutes. This cycle was repeated 20 times. All the coupons displayed the same color after fluorescein test (dark orange) whether they were from the first cycle or the last cycle, which indicated that the grafting successfully passed 20 wash cycles.

Example 45: Grafting on titanium alloy of 3-trimethoxypropylsilyl-cohexyl-methylatedPEI

Sample Preparation and Activation

1 cm² titanium alloy (TiAl₆V₄) samples were sonicated in ethanol for 10 minutes, air-dried, then plasma-activated (atmospheric plasma).

Depositing and Grafting

The solution prepared according to Example 21 (using PEI 750 kDa as a reagent) was deposited on the activated titanium alloy plates by dip-coating, and baked at 110° C. for 3 hours.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated: 4.7±1.9×10¹⁶ cations/cm².

Example 46: Antibacterial activity of surfaces grafted with 3-trimethoxypropylsilyl-cohexyl-methylatedPEI

Contact-Killing Assessment with and without Sample Sterilization by Gamma-Irradiation:

A Staphylococcus epidermidis collection strain was cultured in Brain Heart Infusion (BHI) at 37° C. overnight. According to a modification of the 22196:2011 ISO norm, a 10⁷ CFU/mL bacterial suspension of 20 μL in saline was simultaneously deposited and applied with cover slips on

1 cm² titanium alloy plates were prepared as in Example 43 (control versus 3-trimethoxypropylsilyl-cohexyl-methylatedPEI/TEOS titanium alloy plates by dip-coating). The samples had been sterilized by dipping in 70% ethanol and drying overnight inside a biosafety cabinet. A distinct group of plates (control vs. treated) had been gamma-irradiated at 26 kGy using a ⁶⁰Co source to compare the antibacterial activity of grafted titanium plates before and after industrial-grade sterilization. Plates were then transferred to a stove at 37° C. for 1 hour. Bacterial suspensions under the coverslips were then diluted in 0.9% saline, sonicated for 5 minutes, and vortexed for 45 seconds for serial dilutions, plating on LB agar, and bacterial counting. The bactericidal activity was extremely high and exceeded 4 logs (complete sterilization, no colonies retrieved) on both irradiated and non-irradiated treated titanium alloy plates while there were high bacterial counts on control titanium plates (4.53±0.09 log). FIG. 46 displays Lisogeny Broth (LB) agar plates and is clearly indicative of a high bactericidal activity that persisted after gamma-irradiation of samples. The first two columns from the left correspond to plated dilutions of bacterial suspensions in contact with 70% ethanol-sterilized control titanium alloy plates. The third and fourth columns from the left correspond to plated dilutions of bacterial suspensions in contact with gamma-irradiated control titanium alloy plates. The first column on the right corresponds to plated dilutions of bacterial suspensions in contact with 70% ethanol-sterilized treated titanium plates. The second and third column from the right correspond to plated dilutions of bacterial suspensions in contact with gamma-irradiated treated titanium plates.

Antibacterial Activity of Grafted Surfaces Through Visual Turbidity

A collection Staphylococcus epidermidis strain was cultured overnight in BHI at 37° C. with continuous shaking. The bacteria were then diluted in saline in order to prepare a suspension of 10⁶ CFU/mL. 10 μL were dropped on 1×1 cm² filter paper samples (two control vs two 3-trimethoxypropylsilyl-cohexyl-methylatedPEI-grafted). After 1 hour of incubation at 37° C., the surfaces were placed in fresh BHI (5 mL) and incubated with continuous shaking for 24 h at 37° C. The turbidity was visually compared. FIG. 47. Shows high turbidity with control filter paper (left two) while the BHI solution appears perfectly clear with treated filter paper (right two).

Example 47: Grafting on titanium alloy of acetylcatechol-co-hexyl-PEI

Sample Preparation and Activation

1 cm² TiAl₆V₄ samples were sonicated in ethanol for 10 minutes, air-dried, then piranha activated.

Depositing and Grafting

The solution prepared according to Example 20 (using PEI 750 kDa as a reagent) was deposited on the activated titanium alloy by dip-coating. The sample was then baked for 3 hours at 110° C.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated: 1.8±1.2×10¹⁶ cations/cm².

Example 48: Grafting on stainless steel of acetylcatechol-co-hexyl-PEI

Sample Preparation and Activation

1 cm² stainless steel samples were sonicated in ethanol for 10 minutes, air-dried, then plasma-activated (atmospheric plasma).

Depositing and Grafting

The solution prepared according to Example 20 (using PEI 750 kDa as a reagent) was deposited on the activated stainless steel by dip-coating. The sample was then baked for 3 hours at 110° C.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated: 6.2±2.3×10¹⁴ cations/cm².

Example 49: Grafting of acetylcatechol-co-hexyl-PEI on titanium alloy previously treated with phosphoric acid to create a carpet of P—OH groups

This example describes a method useful to increase the robustness of the grafted layer.

Sample Preparation and Activation

1 cm² TiAl₆V₄ samples were sonicated in ethanol for 10 minutes, air-dried, soaked in 85% H₃PO₄ (phosphoric acid) for 1 hour, and baked at 120° C. overnight. The samples were then sonicated in water for 5 minutes and air-dried.

Depositing and Grafting

The solution prepared according to Example 20 (using PEI 750 kDa as a reagent) was deposited on the activated titanium alloy by dip-coating. The sample was then baked for 3 hours at 110° C.

Surface Charge Determination by Fluorescein Test

Surface cationic density (N⁺/cm²) was calculated: 1.7±0.9×10¹⁵ cations/cm².

Example 50: Titanium-Alloy Implants Covalently Grafted by A Novel Antibacterial Compound

Dramatically Decrease MRSA Biofilm Formation Without the Use of Antibiotics in A Murine Subcutaneous Infection Model

This Example describes a novel ready-to-use antimicrobial compound graftable on titanium-alloy implants (Ti-6Al-4V) developed to form a permanently modified surface that would inhibit the growth of biofilm. Despite significant advancements in material science, surgical site infections (SSI) remain high. This study aimed to demonstrate the in-vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against Methicillin-resistant Staphylococcus aureus (MRSA).

Titanium (Ti) discs were covalently bound with DBG21 (quaternized methyl polyethyleneimine (PEI) (750 kDa) with a propyltrimethoxysilane linker, hexyl side chain (75% by volume in ethanol)+tetraethoxysilane cross linker (25% vol)). Untreated Ti discs were used as controls. All discs were implanted either untreated for control mice or DBG21-treated for treated mice. After implantation, 7 log 10 colony forming units (CFU) of MRSA were injected into the operating site. Mice were sacrificed at day 7 and 14 to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed.

At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (respectively 3.6 median log 10 CFU (99.97%) reduction (p<0.001) and 1.9 median log 10 CFU (98.8%) reduction (p=0.037)) and peri-implant surrounding tissues (respectively 2.7 median log 10 CFU/g (99.8%) reduction (p<0.001) and 5.6 median log 10 CFU/g (99.9997%) reduction (p<0.001)). There were no significant differences between control and treated mice in terms of systemic and local toxicity.

DBG-21 demonstrated a dramatic decrease in biofilm formation and a complete absence of toxicity. Preventing biofilm build-up has been recognized as a key element of SSI prevention.

Clinical Significance: While not wishing to be bound by any particular theory, this example suggests that DBG-21 is a promising candidate for antimicrobial surface modification of medical implants.

In order to proceed with a pre-clinical assessment, the objectives of this study were (1) to assess safety (treated surfaces versus non-treated surfaces implanted subcutaneously in mice in the absence of infection); (2) to assess the antibacterial efficacy of treated implant surfaces versus non-treated implant surfaces using a previously validated methicillin-resistant Staphylococcus aureus (MRSA) infection murine model.

Methods

Animals

In total, 82 BALB/c mice (11-week-old, 22-24 g) were used for the entire study. These animals were housed in a protected area at the small animal facility and were fed ad libitum according to the current recommendations by the European Institute of Health. No fasting was required for this study. Before each experiment, animals were housed for one or two weeks at the animal facility. During this period and for the duration of the study, qualified members of staff checked on animals twice a day and assessed their well-being. The animal facility was authorized by the French authorities. Animal housing and experimental procedures were conducted according to the French and European Regulations and NRC Guide for the Care and Use of Laboratory Animals. All procedures using animals were submitted to the Animal Care and Use Committee C2EA accredited by the French authorities.

Bacterial Strains and Culture Conditions

Methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) strain were kept at −80° C. The strain was streaked on Chapman agar plate and cultured for 18 h at 37° C. A single colony was used to inoculate 9 mL into brain heart infusion (BHI) under agitation for 6 h at 37° C. This bacterial culture was in turn used to inundate a Mueller-Hinton (MH) agar plate that was incubated for 18 h at 37° C. The following day, the MH agar plate was scraped into 10 mL saline (in the presence of glass beads to prevent the formation of clumps) and vortexed to obtain a solution at 10,3 log₁₀ CFU/ml. Successive dilutions were performed in order to obtain the target inoculum size and the bacterial load was determined following plating of the dilutions on MH agar plates.

Titanium-Alloy Implants

Eighty-two grade 5 Ti-6Al-4V discs, 6 mm 0, 0.5 mm thick, were sonicated in pure ethanol for 10 minutes to remove impurities, air-dried, piranha activated (immersed in a 3:1 mixture of sulfuric acid and 30% hydrogen peroxide) in 3 minutes, sonicated in deionized water for 5 min, air dried, dip-coated in an ethanolic polymer solution (DBG21 polymer), and heated at 130° C. for 3 hours to produce covalently bound DBG21-treated discs. All the unbound polymer was removed by sonicating DBG21-treated discs in pure ethanol for 30 minutes. Discs were then air-dried. Control Ti-6Al-4V discs underwent the same activation process without being treated with the polymer solution. All discs were individually stored in double peel packs. Following packaging, all discs underwent subsequent sterilization by 25 kGy irradiation using a Cobalt-60 gamma irradiator.

Tolerance Study

The experimental model was performed as previously described. Briefly, mice were anaesthetized by an intraperitoneal (IP) injection of a mix of ketamine (50 mg/kg) and xylazine (10 mg/kg). The flank on the right side was shaved and then disinfected by 3 consecutive applications of betadine/sterile water. A cutaneous incision of 0.5 cm was made under sterile conditions and an untreated implant (control) or a treated implant (DBG21-treated) was subcutaneously inserted and placed at about 2 cm from the incision site. Five mice received an untreated implant (control) and five mice received a treated implant. The incision was sutured and immediately disinfected and once a day for three days after surgery. Based on the ISO 10993-11:2017 standard, systemic acute and subacute toxicity was evaluated in mice receiving DBG21-treated implants compared to mice receiving untreated implants (controls) in the absence of infection. These mice were daily monitored over an 11-day period (weight, daily clinical score). Clinical scoring included: movement, body posture, fur quality, degree of eye opening, body weight. At day 11, blood samples were collected through intracardiac puncture on all animals previously anaesthetized via a mix of ketamine and xylazine. Euthanasia was performed immediately after the intracardiac puncture by cervical dislocation. A blood biochemical analysis included urea, creatinine, proteins, albumin, liver function tests (LFT) (alkaline phosphatase (ALP), alanine aminotransferase (ALT), glutamate deshydrogenase (GDH), total bilirubin), electrolytes (Na+, K+, Cl—) and glucose. Blood was collected into purple-top potassium EDTA tubes and stored at 4° C. until shipment. The relevant tubes were sent to Cerbavet for analysis and results were available within 24 h.

Efficacy Study

The surgical insertion of implants was performed as described above. The infection was done simultaneously by inoculating 100 μl of the bacterial culture onto the implant (7 Log₁₀ CFU/mouse of ATCC 43300 MRSA strain). Mice received either an untreated implant or a DBG21-treated implant. The incision was sutured and disinfected daily for three days after surgery. The day of infection was referred to as D0. At D7, 36 mice were sacrificed by cervical dislocation performed under anesthesia. The implant was collected and then used for bacterial enumeration. At D14, the same procedure was repeated with the 30 remaining mice (15 mice per group). Histological analysis was performed in 3 mice of each group.

Investigation of Biofilm on Implants and CFU, in Surrounding Tissues

Bacterial Load on the Implant (Biofilm)

Each implant was individually washed under aseptic conditions in an Eppendorf tube (3 successive washing steps with 300, 400 and 500 μL of sterile saline). After the last wash, the implant was suspended into 1 mL of sterile saline, placed into an ultrasonic bath for 3 minutes at room temperature before being vigorously vortexed in order to detach all adherent bacteria from the implant. Several successive dilutions of this suspension (undiluted, 10⁻², 10⁻⁴) were then cultured onto Chapman agar plates for 24-48 h at 37° C. If required, dilutions were repeated in case of unconvincing or inadequate results, the stability of the suspension at 4° C. for 48 h having been previously verified.

Bacterial Load in Surrounding Tissues

Adjacent tissues of each implant were dissected, weighed, resuspended into 1 ml of saline solution and homogenized using a bead beating grinder and lysis system (FastPrep-24 5G, MP Biomedical; 1 cycle of 30 sec at 4 m/sec with 1 ceramic beads). Crushed tissues were serially diluted down to 10⁻⁶ and 10 μL of each dilution was plated by spotting-and-tilt-spreading (SATS) approach on Chapman agar plates.

Histopathological Analysis

During the necropsy at D7 and D14 post-implantation for infected mice and D11 for non-infected mice, the tissue surrounding the implant was excised from animals, then kept in a histological cassette to avoid distortion of the sample and fixed in 10% formaldehyde. All samples (twenty-two subcutaneous murine tissue specimens with titanium implants and apical orientation sutures) were then sent for paraffin-embedding and further histological analysis (Haematoxylin/Eosin/Saffron staining) to Atlantic Bone Screen (ABS, Saint Herblain, France). The samples (subcutaneous tissue with the titanium implant) were processed at ABS. The samples were stored at room temperature in a dedicated location until the start of the experiments. The titanium devices were removed, and the tissue samples were embedded in paraffin and stained with Haematoxylin/Eosin/Saffron. For each block, sections of 3-4 μm were made and placed on Superfrost slides. The slides were dried under a fume hood overnight at room temperature before being used for HES staining. The quality of the histological sections present on each slide was individually assessed before any processing. Similarly, the quality of each staining was individually checked at the end of the procedure. A veterinary pathologist further performed the histological analysis of the produced microscopic slides (graduate of the European College of Veterinary Pathologists). The veterinary pathologist separately documented, illustrated, and commented on any notable events.

Microscopic Examination

All samples (corresponding to a total of 22 sections) were observed by a veterinarian pathologist in a blinded fashion. All significant events were listed, recorded, and documented.

Studied parameters were inflammation, fibrosis, vascularization (neoangenesis) and necrosis.

The scoring was the following:

• • Score 0: absence
  • Score 1: light
  • Score 2: moderated
  • Score 3: heavy

Statistical Analysis

Microbiology statistical analyses were performed with GraphPad Prism software using Mann-Whitney tests. Histological statistical analyses were performed using Kolmogorov-Smirnov tests. The results were expressed as the median±SD. p values were calculated and specified as *: p<0.05; **: p<0.005; ***: p<0.001; ****: p<0.0001.

Results

Impact of surface-treated implants on systemic toxicity

Weight and Clinical Scores

During the 11 days following the subcutaneous implantation, mice gained the normal amount of weight, either in the control group or in the DBG21 treated group. The day following the surgical procedure, mice with treated implants lost ˜10% of their body weight but regained a weight level at day 2 comparable to that of animals with untreated control implants. There was no observed difference in weight between treated and control animals (p>0.05) (FIG. 50). Clinical scores were not statistically different between DBG21-treated and control mice (p>0.05) (FIG. 51). All surgical wounds promptly healed.

Biochemical Tests

Eleven days after subcutaneous implantation, no significant biochemical alterations were recorded, regardless of the group (control or treated). No statistically significant differences between groups were observed (p>0.05) (FIGS. 52A-52K).

Impact of DBG21-Treated Implants on Local Toxicity

Representative pictures of the implant cavity with surrounding tissues in untreated mice and treated mice are displayed respectively in FIG. 53 and FIG. 54. A side-by-side photographic comparison between an untreated and a treated mouse is shown in FIG. 55. After 11 days of subcutaneous implantation, the microscopic analysis of the HES-stained slides showed no significant cytological alterations, no increased fibrosis or inflammation, and no necrosis or neoangiogenesis in the treated group versus controls (p>0.05) (FIGS. 56A-56D).

Evaluation of the Efficacy of DBG21-Treated Versus Untreated Titanium Implants in a MRSA Biofilm Murine Model

At Day 7 post-inoculation, comparable bacterial loads were obtained in control groups (untreated) on implants and surrounding tissues. The median level ±IQR of bacterial colonization remained stable over a 14 day-period of infection in the tissues (7.18±1.75 Log₁₀ CFU/g at Day 7 and 6.55±1.99 Log₁₀ CFU/g at day 14). A slight decrease in the bacterial load was observed on untreated control implants (6.51±0.90 Log₁₀ CFU at Day 7 and 5.84±1.68 Log₁₀ CFU at day 14); thus, the bacterial colonization was overall quite stable.

At day 7 post-inoculation, a significant decrease (p<0.0001) in bacterial load was observed in animals receiving the DBG21-treated implants, (−2.69 Log₁₀ CFU/g of tissues and −3.57 Log₁₀ CFU on implants). Of note, 3 mice out of 18 (16.6%) had both their tissues and implants completely sterilized. At day 14 post-inoculation, this bacterial decrease was still confirmed, with a more pronounced effect in the surrounding tissues compared to the implant (−5.55 Log₁₀ CFU/g of tissues and −1.93 Log₁₀ CFU on implants) (FIGS. 57A-57B). Of note, 10 mice out of 14 (71.4%) with DBG21-treated discs had sterile surrounding tissues while none of the control mice had sterile surrounding tissues.

Also, DBG21-treated implants did not elicit poor tolerance compared to untreated controls in the presence of infection. Body weight remained stable or increased over the 14 day-period, although a slight but not significant decrease of body weight (<5%) was observed in control group n° 9 at day 7.

Histopathological Impact of DBG21-Treated Implants Versus Untreated Titanium-Alloy Implants on Surrounding Tissues in an MRSA Biofilm Model

The use of treated implants led to a tendency of decrease in inflammation, fibrosis, vascularization, and necrosis rates at 7 and 14-days post-implantation, as can be seen in FIGS. 58A-58H and FIGS. 59A-59H (p>0.05). These results indicate that in the presence of an infection, DBG21-treated implants did not generate suppurative and necrotic inflammation over time, unlike control implants with the same bacterial inoculum.

The analysis over time of either control or DBG21-treated implant effects did not highlight any significant differences between the two time points. As observed in FIGS. 59A-59H, the presence of inflammation, fibrosis, vascularization, and necrosis at day 7 persisted at day 14 for the control implants.

DISCUSSION

In this study, no significant differences in weight, clinical scores, or biochemical test results, were observed between the two groups. While not being bound by any particular theory, these results suggest that DBG21-treated implants do not induce any acute or subacute systemic toxicity in mice (ISO 10993-11:2017). The histopathological analysis revealed no differences in local toxicity between the treated and control groups. Taken together, these findings strongly support an excellent biocompatibility profile of DBG21-treated titanium implants. Another important consideration is the non-eluting aspect of this technology. While silver has a therapeutic window that is suboptimal and a toxicity mechanism that is dose-dependent, resorting non-eluting covalently bound nanolayers antimicrobial compounds pave the way for a recognition of the implants as being “modified” and not “temporarily coated”, which should offer higher guarantees of local and systemic nontoxicity. Larger animal data would further support the biocompatibility profile in a specialized bone healing model.

In this investigation, high bacterial median log₁₀ reductions on implants were achieved at both 7 and 14 days postoperatively (respectively 3.6 log₁₀, 99.97% and 1.93 log₁₀, 98.8%) despite the use of a high inoculum (7 log₁₀ CFU), the absence of antibiotics, and the use of a virulent strain with known capability to adhere to biomaterials (MRSA). Furthermore, the bacterial reductions observed in the soft tissues dramatically improve with time between day 7 and day 14. Given that the compound was designed to be non-eluting, it is hypothesized that the strong biofilm inhibition allowed the immune response to build over time and clear the infection in the adequately vascularized soft tissues in view of the stringent model using a high MRSA inoculum with direct injection into the operative site after skin closure in the absence of perioperative antibiotics. This surpasses almost all clinical scenarios of surgical contamination.

Moreover, despite the smaller sample size of the histopathological efficacy sub-study, there was a clear tendency of decrease of inflammation, fibrosis, vascularization, and necrosis around the treated versus control discs. In the presence of infection, all these positive findings (bacterial counts and histopathological analysis) show that DBG21-treated discs were able to strongly mitigate infection, or even eradicate infection in some of the mice, despite a high MRSA bacterial load and without the use of antibiotics.

Comparison of the bacterial reductions on titanium implants between DBG21 and data from previously published peer-reviewed studies (antimicrobial coatings and surface modifications tested against Staphylococcus species, Table 1):

TABLE 1
Comparative data for various antibacterial surface modification technology.
								Duration
Authors	Technology	Strain	Animals	N	Inoc.	BTP	MR	(days)
Hashimoto et al.	HA/Silver coating	MRSA	Rats	12	6	1	0.35	1
Ueno et al.	HA/Silver coating	MRSA	Rats	10	8	7	0.41	7
Shimazaki et al.	HA/Silver coating	MRSA	Rats	10	6	3	1.4	3
Gerits et al.	Covalent SPI031	MRSA	Mice	26	7	4	1.7	4
Chen et al.	Melimine peptide	MRSA	Rats	34	5	5	2	7
	coating
Kucharikova et al.	Covalent	MSSA	Mice	19	7	4	2.5	4
	Vancomycin
Skovdal et al.	Ultradense PEG	S. Epidermidis	Mice	31	9	5	2.75	5
	coating
Tilmaciu et al.	Covalent Ag-loaded	S. Epidermidis	Mice	10	4	14	3.6	14
	phosphonates
Current study	DBG21	MRSA	Mice	65	7	7	3.6	14
HA = hydroxyapatite;
PEG = polyethylene glycol;
MRSA = methicillin-resistant staphylococcus aureus;
Inoc = inoculum (Log10 CFU);
BTP = best timepoints (days);
MR = max reduction (Log10 CFU)

The bacterial reductions reported on implants and in the surrounding tissues in this study outperformed the scientific literature on comparable subcutaneous infection rodent models with titanium implants. Indeed, most published studies do not exceed 2.5-2.75 log₁₀ bacterial reductions both in the surrounding tissues and on implants for bacterial strains with less virulence (Staphylococcus epidermidis), lower inocula (6 log₁₀ and below), and shorter time points (under 7 days). Also, most of the processes described in the literature are exceedingly complex, require the use of toxic reagents and/or solvents, and do not meet standards of scalability in the orthopaedic industry.

Interestingly, the bacterial log reductions observed in this study in the surrounding tissue that improved between day 7 and 14 were not found in the literature pertaining to covalently bound antimicrobials. Typically, authors reported no effect on surrounding tissues for covalently bound antimicrobials. This could be due to their lower bactericidal effect on contact and thus lower biofilm inhibition since biofilm and tissue bacterial burden are not too separate entities but completely interdependent mechanisms. As was shown over 60 years ago, it is the presence of the foreign body that allows the infection to persist despite low inoculate.

In some embodiments, the antibacterial effect was more pronounced on treated implants at D7 than D14. Although not wishing to be bound by any particular theory, this result is likely due to a limitation of the model to perform true bacterial enumeration on implants at day 14. In some embodiments, a capsule formed on several discs at day 14 in the presence of infection. Because of this protocol, the capsule cannot be removed to count bacteria on the titanium surface. Therefore, the bacterial reduction described at day 14 reflects what occurred either on the titanium surface or on a capsule, based on the amount of tissue response in the presence of the infection. In some embodiments, the soft tissues were sterilized in most mice in the same timeframe. In some embodiments, the study is performed using a large animal trial to provide data on efficacy in a bone-relevant model and osteointegration. This Example demontrates the use of antimicrobial surface modification of medical devices, not solely for orthopaedic applications, titanium-alloy being a gold-standard metal for numerous other applications. Small animal models are useful to permit the collection of more complete safety and efficacy data by the use of large sample sizes.

CONCLUSION

Overall, these results showed that the MRSA biofilm was drastically reduced by up to 99.97% in mice receiving DBG21-treated titanium-alloy implants as compared to untreated control implants without causing measurable toxicity. This level of protection provided by a non-eluting surface treatment despite a high bacterial inoculum of a virulent strain is novel and can be useful to change the way implant-related infections in humans are treated.

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A number of patent and non-patent publications are cited herein in order to describe the state of the art to which this invention pertains. The entire disclosure of each of these publications is incorporated by reference herein.

While certain embodiments of the present invention have been described and/or exemplified above, various other embodiments will be apparent to those skilled in the art from the foregoing disclosure. The present invention is, therefore, not limited to the particular embodiments described and/or exemplified, but is capable of considerable variation and modification without departure from the scope and spirit of the appended claims.

Claims

1. A composition comprising a polymer comprising at least one moiety of formula (XVIIa) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

2. The composition of claim 1, wherein the polymer comprises at least one moiety of formula (XVIIb) or formula (XVIIe):

3. The composition of claim 2, wherein the polymer comprises at least one moiety of formula (XVIIj):

4. The composition of any one of claims 1-3, wherein the polymer further comprises at least one moiety of formula (III):

5. The composition of claim 1 or 4, wherein the polymer comprises at least one moiety of formula (XVIIc):

6. The composition of any one of claims 1-5, wherein the polymer further comprises at least one moiety of formula (VII):

7. The composition of claim 1 or 6, wherein the polymer comprises at least one moiety of formula (XVIIg):

8. The composition of any one of claims 1-7, wherein the polymer comprises at least one moiety of formula (XVIIh):

9. The composition of claim 8, wherein the polymer comprises at least one moiety of formula (XVIIf):

10. The composition of claim 8, wherein the polymer comprises at least one moiety of formula (XVIId):

11. A composition comprising a polymer comprising at least one moiety of formula (XXI) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

12. The composition of claim 11, wherein the polymer comprises at least one moiety of formula (XXIa) or formula (XXII):

13. The composition of claim 12 or 13, wherein the polymer comprises at least one moiety of formula (XXIb):

14. The composition of any one of claims 11-13, wherein the polymer further comprises at least one moiety of formula (III):

15. The composition of any one of claims 11-14, wherein the polymer comprises at least one moiety of formula (XXId):

16. The composition of claim 11 or 12, wherein the polymer comprises at least one moiety of formula (XXIIa):

17. The composition of claim 11 or 12, wherein the polymer comprises at least one moiety of formula (XXIIb):

18. The composition of claim 11 or 17, wherein the polymer further comprises at least one moiety of formula (VII):

19. The composition of claim 11, wherein the polymer comprises at least one moiety of formula (XXIIc):

20. A composition comprising a polymer comprising at least one moiety of formula (II) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

21. The composition of claim 20, wherein the polymer further comprises at least one moiety of formula (III):

22. The composition of claim 20 or 21, wherein the polymer comprises at least one moiety of formula (IV):

23. A composition comprising a polymer comprising at least one moiety of formula (V) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

24. The composition of claim 23, wherein the polymer comprises at least one moiety of formula (VI):

25. The composition of claim 23 or 24, wherein the polymer further comprises a moiety of formula (VII):

26. The composition of any one of claims 23-25, wherein the polymer comprises at least one moiety of formula (VIII):

27. The composition of any one of claims 1-26, wherein the polymer comprises polyvinylpyridine (PVP), polyvinylbenzylchloride, polyethylenimine (PEI), propynyl methacrylate, polyethylene, polyacrylamide, polystyrene, polyvinylalcohol, polyallylamine, polyallylalcohol, polyvinylbenzyl, polyamine, polymethacrylate, polyether, poly(ethylene-alt-succinimide), poly(diallyldimethylammonium), or a C3-C22 alkyne.

28. A composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXa), formula (IXb), or formula (IXh) and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

29. The composition of claim 28, wherein the PEI polymer comprises at least one moiety of formula (IXc) or (IXd):

30. The composition of claim 28 or 29, wherein the PEI polymer comprises one or more of the following moieties:

31. The composition of any one of claims 28-30, wherein R2 is selected from methyl and hexyl.

32. The composition of any one of claims 28-31, wherein PEI polymer comprises one or more of the following moieties, and one R2 is methyl and one R2 is hexyl:

33. The composition of any one of claims 28-32, wherein the PEI polymer comprises at least one moiety of formula (IXe), or any substructure thereof:

34. A composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXf), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

35. A composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (IXg), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent thereof:

36. A composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa), and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

37. The composition of claim 36, wherein the PEI polymer comprises at least one of the following moieties

38. The composition of claim 37, wherein each R2 is hexyl.

39. The composition of claim 37 or 38, wherein at least one R2 is methyl.

40. The composition of any one of claims 36-39, wherein the PEI polymer comprises one or more of the following moiety, wherein one R2 is hexyl and one R2 is methyl:

41. The composition of any one of claims 36-40, wherein v is 3.

42. A composition comprising a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIb), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

43. A composition comprising polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIc), or any substructure thereof, and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

44. The composition of any one of claims 36-43, wherein each moiety of formula (XIa)

45. The composition of any one of claims 1-44, wherein the at least one grafting enhancer and/or grafting adjuvant is a cross-linking reagent.

46. The composition of claim 45, wherein the cross-linking reagent is selected from tetramethylorthosilicate, trimethylmethoxyorthosilicate, trimethylethoxyorthosilicate, dimethyldimethoxyorthosilicate, dimethyldiethoxyorthosilicate, methyltrimethoxyorthosilicate, methyltriethoxyorthosilicate, tetramethoxyorthosilicate, tetraethoxyorthosilicate (TEOS), methyldimethoxyorthosilicate, methyldiethoxyorthosilicate, dimethylethoxyorthosilicate, dimethylvinylmethoxyorthosilicate, dimethylvinylethoxyorthosilicate, tetraethylorthosilicate, methylvinyldimethoxyorthosilicate, methylvinyldiethoxyorthosilicate, diphenyldimethoxyorthosilicate, diphenyldiethoxyorthosilicate, phenyltrimethoxyorthosilicate, phenyltriethoxyorthosilicate, octadecyltrimethoxyorthosilicate and octadecyltriethoxyorthosilicate, 1,3-Disiloxanediol, 1,1,3,3-tetramethyl, 1,1,3,3-tetramethyldisiloxane-1,3-diol, 1,1,3,3-tetramethoxy-1,3-dimethyldisiloxane, tetraethoxy-1,3-dimethyldisiloxane, and 1,5-diethoxyhexamethyltrisiloxane.

47. A surface having the composition of any one of claims 1-46 grafted thereon.

48. The surface of claim 47, wherein the surface comprises a material selected from metals such as titanium and titanium alloys, iron, and steel; metal oxides; ceramics; polymers such as polyethylene (low and high reticulation for use in biomedical implants, after prior plasma activation), teflon (after prior plasma activation), polyethylene terephthalate (after prior plasma activation), and polypropylene (low and high density, after prior plasma activation), silicones, rubbers, latex, plastics, polyanhydrides, polyesters, polyorthoesters, polyamides, polyacrylonitrile, polyurethanes, polyethylene, polytetrafluoroethylene, polyethylenetetraphthalate and polyphazenes; paper; leather; textiles or textile materials such as cotton, jute, linen, hemp, wool, animals hair and silk, synthetic fabrics such as nylon and polyester; textile material comprising fibers comprising fiber material such as acrylic polymers, acrylate polymers, aramid polymers, cellulosic materials, cotton, nylon, polyolefins, polyester, polyamide, polypropylene, rayon, wool, spandex, silk, and viscose; silicon; wood; glass; cellulosic compounds; and gels and fluids not normally found within the human body.

49. A method of controlling the growth of at least one bacteria, fungi, protozoa, or virus, the method comprising grafting a composition of any one of claims 1-47 onto a surface.

50. The method of claim 49, wherein the bacteria is a gram-positive bacteria selected from M. tuberculosis (including multi drug resistant TB and extensively drug resistant TB), M bovis, M typhimurium, M bovis strain BCG, BCG substrains, M avium, M intracellulare, M africanum, M kansasii, M marinum, M ulcerans, M avium subspecies paratuberculosis, Staphylococcus aureus (including Methicillin-resistant Staphylococcus aureus (MRSA)), Staphylococcus epidermidis, Staphylococcus equi, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Listeria ivanovii, Bacillus anthraces, B. subtilis, Nocardia asteroides, and other Nocardia species, Streptococcus viridans group, Peptococcus species, Peptostreptococcus species, Actinomyces israelii and other Actinomyces species, Propionibacterium acnes, Clostridium tetani, Clostridium perfringens, Clostridium botulinum, other Clostridium species, and Enterococcus species.

51. The method of claim 49, wherein the bacteria is a gram-negative bacteria selected from Pseudomonas aeruginosa, other Pseudomonas species, Campylobacter species, Vibrio cholerae, Ehrlichia species, Actinobacillus pleuropneumoniae, Pasteurella haemolytica, Pasteurella multocida, other Pasteurella species, Legionella pneumophila, other Legionella species, Salmonella typhi, other Salmonella species, Shigella species, Brucella abortus, other Brucella species, Chlamydi trachomatis, Chlamydia psittaci, Coxiella burnetti, Escherichia coli, Neiserria meningitidis, Neiserria gonorrhea, Haemophilus influenzae, Haemophilus ducreyi, other Hemophilus species, Yersinia pestis, Yersinia enterolitica, other Yersinia species, Escherichia coli, Escherichia hirae, and other Escherichia species, as well as other Enterobacteriacae, Burkholderia cepacia, Burkholderia pseudomallei, Francisella tularensis, Bacteroides fragilis, Fusobascterium nucleatum, Provetella species, Cowdria ruminantium, Klebsiella species, and Proteus species.

52. The method of claim 49, wherein the virus is selected from influenza, Middle East respiratory syndrome-related coronavirus (MERS-CoV), rhinovirus, polio, measles, Ebola, Coxsackie, West Nile, yellow fever, Dengue fever, lassa, lymphocytic choriomeningitis, Junin, Machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), parainfluenza, Tacaribe, and Pichinde viruses.

53. A coating comprising metal oxide nanoparticles and one or more compositions from any one of claims 1-46.

54. The coating of claim 53, wherein a plurality of the metal oxide nanoparticles are substantially in contact with a surface.

55. The coating of claim 53, wherein the one or more polymers are grafted onto the surface of one or more of metal oxide nanoparticles.

56. The coating of any one of claims 53-55, wherein the metal oxide nanoparticles comprise titanium oxide nanoparticles.

57. A solution comprising an alcohol and at least one composition of claims 1-46.

58. The solution of claim 57, wherein the alcohol is selected from ethanol, methanol, n-propanol, isopropanol, t-butyl alcohol, and t-amyl alcohol.

59. The solution of claim 57 or 58, wherein the solution is stable for up to 1 day, up to 2 days, up to 3 days, up to 4 days, up to 5 days, up to 6 days, up to 7 days, up to 2 weeks, up to 3 weeks, up to 1 month, up to 2 months, up to 3 months, up to 4 months, up to 5 months, up to 6 months, up to 7 months, up to 8 months, up to 9 months, up to 10 months, up to 11 months, up to 1 year, or up to 2 years after preparation.

60. A method of preparing the composition of any one of claims 1-46, the method comprising mixing at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, with at least one polymer of any one of claims 1-44.

61. A method of preparing the solution of any one of claims 57-59, the method comprising adding at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, to a solution comprising an alcohol and at least one polymer of any one of claims 1-44.

62. The composition of any one of claims 1-46, the solution of any one of claims 57-59, or the method of claim 60 or 61, comprising the polymer of any one of claims 1-44 in an amount of about 99.9% to about 50% (v/v), about 99.9% to about 60% (v/v), about 99.9% to about 70% (v/v), or about 99.5% to about 75% (v/v), and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% to about 50% (v/v), about 0.1% to about 40% (v/v), about 0.1% to about 30% (v/v), or about 0.5% to about 25% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant.

63. The composition of any one of claims 1-46, the solution of any one of claims 57-59, or the method of claim 60 or 61, comprising the polymer of any one of claims 1-44 in an amount of about 99.9% (v/v), 99.8% (v/v), 99.7% (v/v), 99.6% (v/v), 99.5% (v/v), 99.4% (v/v), 99.3% (v/v), 99.2% (v/v), 99.1% (v/v), 99% (v/v), 98% (v/v), 97% (v/v), 96% (v/v), 95% (v/v), 94% (v/v), 93% (v/v), 92% (v/v), 91% (v/v), 90% (v/v), 85% (v/v), 80% (v/v), 75% (v/v), 70% (v/v), 65% (v/v), 60% (v/v), 55% (v/v), or 50% (v/v), and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, in an amount of about 0.1% (v/v), 0.2% (v/v), 0.3% (v/v), 0.4% (v/v), 0.5% (v/v), 0.6% (v/v), 0.7% (v/v), 0.8% (v/v), 0.9% (v/v), 1% (v/v), 2% (v/v), 3% (v/v), 4% (v/v), 5% (v/v), 6% (v/v), 7% (v/v), 8% (v/v), 9% (v/v), 10% (v/v), 15% (v/v), 20% (v/v), 25% (v/v), 30% (v/v), 35% (v/v), 40% (v/v), 45% (v/v), or 50% (v/v) of the total volume of the the at least one polymer, compound, and/or graftable substrate and the at least one grafting enhancer and/or grafting adjuvant.

64. The composition of any one of claims 1-46, the solution of any one of claims 57-59, or the method of claim 60 or 61, comprising the polymer of any one of claims 1-44 and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, at a ratio between about 400:1 and about 1:1, between about 300:1 and about 2:1, or between about 200:1 and about 3:1.

65. The composition of any one of claims 1-46, the solution of any one of claims 57-59, or the method of claim 60 or 61, comprising the polymer of any one of claims 1-44 and the at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent, at a ratio of about 400:1, about 350:1, about 300:1, about 250:1, about 200:1, about 150:1, about 100:1, about 50:1, about 40:1, about 30:1, about 20:1, about 10:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1.

66. A method of preparing a conjugated biomolecule, the method comprising grafting a catechol moiety of formula (Ib) on to a surface, and reacting the compound of formula (Ib′) with a biomolecule of formula (XLb):

67. The method of claim 66, wherein X comprises a reactive group and/or a leaving group selected from halo, —SH, —N3,

68. The method of claim 66 or 67, wherein R is selected from

69. The method of any one of claims 66-68, wherein Z′ comprises a reactive group and/or a leaving group selected selected from halo, —SH, —N3,

70. A solution comprising an alcohol and a polyethylenimine (PEI) polymer comprising at least one moiety of formula (XIa), and at least one grafting enhancer and/or grafting adjuvant, optionally a cross-linking reagent:

71. The solution of claim 70, wherein the PEI polymer comprises one or more of the following moiety, wherein one R2 is hexyl and one R2 is methyl:

72. The solution of claim 70, wherein each R3 is methoxy and v is 3.

73. The solution of claim 70, wherein the grafting enhancer and/or grafting adjuvant is a cross-linking reagent, wherein the cross-linking agent is or comprises tetraethoxyorthosilicate (tetraethoxysilane, TEOS).

74. The solution of claim 70, wherein the molecular weight of the PEI polymer is of a range of about 700 kDa to about 800 kDa, optionally about 750 kDa.