Weed-resistant coatings and methods for their production and use

Description

[0001] The present invention relates to a copolymer, a biofouling-resistant medical device, and a method of making a biofouling-resistant medical device.BACKGROUND

[0002] Hospital acquired infections (HAIs) cause over 100,000 deaths per year and over $30 billion in direct healthcare cost. In some cases, medical devices implanted into the body are the source of the HAI. Planktonic bacteria adhere to the surface of the medical devices and begin to grow into resilient biofilms that become more resistant to antibiotics and disinfecting agents than in the planktonic state.

[0003] In this context, WO 2019 / 079765 A1 discloses surfaces and coating compositions having antifouling, antithrombotic, and antibacterial properties and methods of making, WO 2018 / 213627 A1 discloses zwitterionic monomers, polyzwitterionic polymers formed therefrom, surface functionalization and surface modification, US 2012 / 0258313 A1 discloses coating agents and coated articles, and US 2015 / 0025168 A1 discloses synthesis and micro- / nanostructuring of surface-attached crosslinked antimicrobial and / or antibiofouling polymer networks.SUMMARY

[0004] Described herein are polymers to be used in biofouling-resistant coatings, biofouling-resistant coatings, methods of making biofouling-resistant coatings, biofouling-resistant medical devices, and methods of making biofouling-resistant medical devices.

[0005] In one aspect, the present invention provides a copolymer comprising: a) a repeating unit of Formula (VII): wherein, each R 1a< and R 1b< is independently selected from hydrogen and halogen; each R 2a< and R 2b< is independently selected from halogen, -CN, and optionally substituted C 1 -C 6 fluoroalkyl; each A 1< and A 2< is independently selected from -C(=O)-, -S(=O)-, -S(=O) 2 -, and -S(=O)(=NR 3c< )-; each B 1< and B 2< is independently selected from -O- and -NR 3c< -; Z 1< is -(CR 6c< R 6d< ) s -; each R 4c< , R 4d< , R 5d< , R 5e< , R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 11a< , R 11b< , and R 11c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; and s is an integer selected from 1, 2, 3, 4, and 5; b) a repeating unit of Formula (VIII): wherein, A 3< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 3< is -O- or -NR 3c< -; D is -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; Z 2< is -(CR 6c< R 6d< ) t -; Z 3< is -(CR 6c< R 6d< ) p -; each R 3a< and R 3b< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted benzyl; each R 6c< and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 12a< , R 12b< , and R 12c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; t is an integer selected from 1, 2, 3, 4, or 5; p is an integer selected from 1, 2, 3, 4, or 5; and wherein the repeating unit of Formula (VIII) is charged or zwitterionic; and c) a repeating unit of Formula (IX): wherein, A 4< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 4< is -O- or -NR 3c< -; Z 4< is -(CR 6c< R 6d< ) k -; E is -CN, -OR 9a< , -NR 9a< R 9b< , -NR 9a< R 9b< R 9c+< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 6 fluoroalkyl, -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; each R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 9b< , R 9c< , R 13a< , R 13b< , and R 13c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; and k is an integer selected from 1, 2, 3, 4, or 5.

[0006] In another aspect, the present invention provides a biofouling-resistant medical device, wherein a surface of the medical device is coated with a compound as described above.

[0007] In yet another aspect, the present invention provides a method of making a biofouling-resistant medical device, comprising: a) contacting a surface of a device with a mixture comprising a copolymer as described above; and b) treating the surface of the device of step a) with a heat source for a time sufficient to undergo thermografting of the copolymer onto the surface of the device, thereby making the biofouling-resistant device. BRIEF DESCRIPTION OF THE FIGURES

[0008] The accompanying figures illustrate several aspects and together with the description serve to explain and not to limit the scope of the present invention. FIG. 1 illustrates representative photografting of poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate) (PFPA-PSB copolymer) to a silicone surface. FIG. 2Aillustrates representative water advancing contact angle (upper image) and receding contact angle (lower image) on an unmodified silicone surface and (b) PFPA-PSB copolymer modified silicone surface. FIG. 2Billustrates representative water advancing contact angle (upper image) and receding contact angle (lower image) on a PFPA-PSB copolymer modified silicone surface. FIG. 3Aillustrates high density of Escherichia coli adhesion to unmodified silicone surface forming an elastic film, which fractured upon surface drying. FIG. 3Billustrates very low density of Escherichia coli adhesion to poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate)-modified silicone surface. FIG. 4 illustrates the structure of PFPA-PSB copolymer. FIG. 5A illustrates chemical structure of polydimethylsiloxane and polysulfobetaine. FIG. 5B illustrates XPS spectra of a PFPA-PSB modified PDMS substrate, showing the successful grafting of PSB on the organic substrate.

[0009] Additional advantages of the present invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the present invention. The advantages of the present invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present invention which is set out in the appended claims.DETAILED DESCRIPTION

[0010] Hospital acquired infections (HAIs) cause over 100,000 deaths per year and over $30 billion in direct healthcare cost. Despite reduction of HAIs in recent years through improved antiseptic technique, surgical procedure, and diagnosis, HAIs declines are slowing down indicating the need for new preventative methods. In some instances, medical devices implanted into the body are the source of infection. It is estimated that 60-70% of HAIs are associated with the use of implantable medical devices. Planktonic bacteria adhere to the surface of the medical devices and begin to grow into resilient biofilms that become more resistant to antibiotics and disinfecting agents than in the planktonic state. As the biofilm grows and the cells continue to proliferate, the extracellular matrix scaffolding (made up of proteins and polysaccharides) bursts open, releasing more bacteria into the body. The body can no longer stave off infection and strong antibiotics must be used to fight the infectious cells. The use of strong antibiotics has led to the existence of antibiotic resistant bacteria, also known as superbugs, which can no longer be treated with conventional antibiotics.

[0011] Without the initial adhesion of planktonic cells to the surface of a material, the biofilm formation is prevented or reduced. Several researchers have identified the attractive forces that cause organic material to adhere to polymeric surfaces: hydrophobic interactions and electrostatic interactions (van der Waals forces) between the organic materials and polymer surface. Using self-assembled monolayers, Whitesides et al. surveyed several functional groups to determine surface functionalities that promote or hinder the non-specific adsorption of proteins. (Whitesides, G. M. A survey of structure-property relationships of surfaces that resist the adsorption of protein. Langmuir, 2001, 17 (18), pp 5605-5620). The functional groups that exhibited the lowest adhesion were electrostatically neutral hydrophilic moieties that contained hydrogen bond donating groups. From these design rules, many material coatings have been developed and shown to reduce adhesion of proteins and microorganisms. However, these coating are substrate dependent and / or require exotic reaction conditions that are not compatible for wide-scale use. In some cases, several polymers coatings and surface modifications have been developed to repel these interactions to reduce / prevent the formation of biofilms on surfaces. In some instances, the coating should have the following chemical requirements to be used as an anti-fouling surface: a) the coating should be hydrophilic; b) the coating should consist of mostly of hydrogen bond acceptors; and c) the coating should be electrostatically neutral. However, due to the water-solubility of hydrophilic coatings, the coating material should be covalently bound to the polymeric material for long-term effects.

[0012] In some instances, medical grade silicone is used in medical and health care industry. Its market currently undergoes a rapid growth and is projected to reach $7.23 billion by 2021. Medical grade silicone generally includes polydimethylsiloxane (PDMS) fluids and elastomers. Due to their good chemical stability, matching mechanical properties with human tissues, and no-requirements for plasticizers, PDMS elastomers generally have excellent biocompatibility, and are used in medical devices and biomedical implants such as catheters and pacemakers. PDMS elastomers also have high transparency and easy processability. Therefore, PDMS elastomers have found broad applications in fabricating microfluidic devices, which provide low-cost, simple, and robust systems for diagnosing diseases (Whitesides, G. M. The origins and the future of microfluidics. Nature 2006, 442 (7101), 368-373). However, PDMS elastomers also have a low surface energy of about 20 mN / m. Bacteria, platelets, proteins, and other biomolecules tend to adhere to the hydrophobic surfaces of PDMS elastomers (Hron, P. Hydrophilisation of silicone rubber for medical applications. Polymer international 2003, 52 (9), 1531-1539). For silicone medical implants, bacterial adhesion and biofilm formation may lead to the failure of medical devices, severe infection, and even death of patients. For disease diagnosis devices based on PDMS microfluidics, proteins and other biomolecules fouling on the PDMS surfaces can significantly reduce the sensitivity of these devices, and may even lead to complete device-failure if blocking of the microfluidic channels occurs (Zhou, J. et al. Recent developments in PDMS surface modification for microfluidic devices. Electrophoresis 2010, 31 (1), 2-16).

[0013] Hydrophilic treatment of the PDMS surfaces was found to be one of the strategies to alleviate or prevent the problem of biofouling (Keefe, A. J. et al. Suppressing surface reconstruction of superhydrophobic PDMS using a superhydrophilic zwitterionic polymer. Biomacromolecules 2012, 13 (5), 1683-1687). Some conventional methods of making PDMS surfaces hydrophilic include oxidation of the surfaces by oxygen plasma, UV-ozone, or corona discharge. However, these modifications are only temporary because PDMS has an extremely low glass transition temperature of about -120 °C and therefore the PDMS chains are highly mobile at room temperature. The PDMS chains are able to rearrange and recover the hydrophobic surface of PDMS elastomers within a time window of a few hours. In some cases, other methods seeking to make long-lasting hydrophilic PDMS surfaces take many steps and involve radical reaction or polymerization. These steps have to be performed in closed containers, and / or under the protection of inert gas. Due to the higher solubility of oxygen relative to nitrogen in PDMS, in some instances it takes long time to remove oxygen from PDMS so that the radical reaction can proceed efficiently. These strict reaction conditions significantly increase the cost and limit industrial applicability of these reactions.

[0014] The biofouling-resistant coatings described herein comprise charged or zwitterion compounds comprising phenyl-azide moieties. In some instances, biofouling comprises microfouling or macrofouling. Microfouling comprises formation of microorganism adhesion (e.g., bacteria adhesion) and / or biofilm. Biofilm is a group of microorganism which adheres to a surface. In some instances, the adhered microorganisms are further embedded in a self-produced matrix of extracellular polymeric substance, which comprises a polymeric conglomeration of extracellular DNA, protein, and polysaccharides. Macrofouling comprises attachment of larger organisms.

[0015] Charged and / or zwitterionic compounds bind water molecules via electrostatically induced hydration. In such cases, charged and / or zwitterionic materials exhibit surface resistance to protein / cell / bacterial adhesion, biofilm formation, and / or macrofouling. The charged or zwitterion compounds described herein comprise copolymers. The charged or zwitterion copolymers described herein may be obtained via polymerization reaction. The polymerization reaction may be addition polymerization, atomic transfer radical polymerization (ATRP), coordination polymerization, free-radical polymerization, nitroxide-mediated radical polymerization (NMP), reversible addition-fragmentation chain-transfer polymerization (RAFT), or ring-opening metathesis polymerization (ROMP). The ionic polymerization may be anionic polymerization or cationic polymerization. The polymerization reaction may be reversible-deactivation polymerization (RDP). The polymerization reaction may be free-radical polymerization. The polymerization reaction may be atomic transfer radical polymerization (ATRP). Biofouling-resistant coatings comprising charged or zwitterion copolymers may be grafted onto a polymer surface of a medical device under a UV exposure. Charged or zwitterion copolymers may be grafted onto a silicone-comprising surface of a medical device under a UV exposure. Charged or zwitterion copolymers may be grafted onto a surface of a medical device under a UV exposure. Charged or zwitterion copolymers may be grafted onto a silicone-comprising surface of a medical device under a UV exposure. Charged or zwitterion may be grafted onto a polymer surface of a medical device under a UV exposure. Charged or zwitterion copolymers may be grafted onto a silicone-comprising polymer surface of a medical device under a UV exposure.

[0016] A charged or zwitterion copolymer modified medical device may comprise anti-fouling properties and may be used to prevent and / or to reduce the development of biofouling. The charged or zwitterion coatings may prevent and / or reduce the attachment of microorganisms, plants, algae, or animals to a surface.

[0017] In the following, compounds to be used to prepare the charged or zwitterion copolymers as well as the charged or zwitterion copolymers themselves are described.Compounds

[0018] The copolymer of the present invention comprises: a) a repeating unit of Formula (VII): wherein each R 1a< and R 1b< is independently selected from hydrogen and halogen; each R 2a< and R 2b< is independently selected from halogen, -CN, and optionally substituted C 1 -C 6 fluoroalkyl; each A 1< and A 2< is independently selected from -C(=O)-, -S(=O)-, -S(=O) 2 -, and -S(=O)(=NR 3c< )-; each B 1< and B 2< is independently selected from -O- and -NR 3c< -; Z 1< is -(CR 6c< R 6d< ) s -; each R 4c< , R 4d< , R 5d< , R 5e< , R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 11a< , R 11b< , and R 11c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; and s is an integer selected from 1, 2, 3, 4, and 5; b) a repeating unit of Formula (VIII): wherein, A 3< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 3< is -O- or -NR 3c< -; D is -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; Z 2< is -(CR 6c< R 6d< ) t -; Z 3< is -(CR 6c< R 6d< ) p -; each R 3a< and R 3b< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted benzyl; each R 6c< and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 12a< , R 12b< , and R 12c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; t is an integer selected from 1, 2, 3, 4, or 5; p is an integer selected from 1, 2, 3, 4, or 5; and wherein the repeating unit of Formula (VIII) is charged or zwitterionic; and c) a repeating unit of Formula (IX): A 4< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 4< is -O- or -NR 3c< -; Z 4< is -(CR 6c< R 6d< ) k -; E is -CN, -OR 9a< , -NR 9a< R 9b< , -NR 9a< R 9b< R 9c+< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 6 fluoroalkyl, -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; each R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 9b< , R 9c< , R 13a< , R 13b< , and R 13c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; and k is an integer selected from 1, 2, 3, 4, or 5.

[0019] The repeating unit of Formula (IX) may be charged or zwitterionic.

[0020] Each R 1a< and R 1b< may be independently halogen. Each R 1a< and R 1b< may be independently F or Cl. Each R 1a< and R 1b< may be F. Each R 2a< and R 2b< may be independently selected from halogen, - CN, and optionally substituted C 1 -C 6 fluoroalkyl. Each R 2a< and R 2b< may be independently selected from halogen, -CN, and -CF 3 . Each R 2a< and R 2b< may be independently selected from F, Cl, -CN, and -CF 3 . Each R 2a< and R 2b< may be independently halogen. Each R 2a< and R 2b< may be F. Each R 2a< and R 2b< may be -CN. Each R 2a< and R 2b< may be independently C 1 -C 6 fluoroalkyl. Each R 2a< and R 2b< may be -CF 3 . Each R 1a< , R 1b< , R 2a< , and R 2b< may be F.

[0021] A 1< may be -S(=O) 2 -. A 1< may be -C(=O)-. A 2< may be -S(=O) 2 -. A 2< may be -C(=O)-. A 3< may be -S(=O) 2 -. A 3< may be -C(=O)-. A 4< may be -S(=O) 2 -. A 4< may be -C(=O)-. A 1< may be -S(=O) 2 - and each A 2< , A 3< , and A 4< may be -C(=O)-. Each A 1< , A 2< , A 3< , and A 4< may be -C(=O)-.

[0022] Each B 1< , B 2< , and B 3< may be independently -O- or -NR 3c< -. B 1< may be -O-. B 1< may be -NR 3c< -. B 2< may be -O-. B 2< may be -NR 3c< -. B 3< may be -O-. B 3< may be -NR 3c< -. B 4< may be -O-. B 4< may be - NR 3c< -.

[0023] Each R 3c< may be independently hydrogen, optionally substituted C 1 -C 4 alkyl, or optionally substituted aryl. R 3c< may be hydrogen. R 3c< may be optionally substituted C 1 -C 4 alkyl. R 3c< may be - CH 3 . Each R 3c< may be hydrogen or -CH 3 . R 3c< may be optionally substituted aryl. R 3c< may be optionally substituted phenyl.

[0024] D may be -S(=O) 2 OR 9a< or -C(=O)OR 9a< . D may be -S(=O) 2 OR 9a< . D may be -C(=O)OR 9a< . R 9a< may be hydrogen or -CH 3 . R 9a< may be hydrogen. R 9a< may be -CH 3 .

[0025] D may be -S(=O) 2 O -< or -C(=O)O -< . D may be -S(=O) 2 O -< . D may be -C(=O)O -< .

[0026] E may be -NR 9a< R 9b< R 9c+< or -S(=O) 2 OR 9a< . E may be -NR 9a< R 9b< R 9c+< or -C(=O)OR 9a< .

[0027] E may be -NR 9a< R 9b< R 9c+< . Each R 9a< , R 9b< , and R 9c< may be independently hydrogen or C 1 -C 4 alkyl. Each R 9a< , R 9b< , and R 9c< may be independently hydrogen or -CH 3 . R 9a< may be hydrogen. R 9a< may be -CH 3 . R 9b< may be hydrogen. R 9b< may be -CH 3 . R 9c< may be hydrogen. R 9c< may be -CH 3 .

[0028] E may be -S(=O) 2 OR 9a< . E may be -C(=O)OR 9a< . Each R 9a< may be hydrogen or -CH 3 . R 9a< may be hydrogen. R 9a< may be -CH 3 .

[0029] E may be -S(=O) 2 O -< or -C(=O)O -< . E may be -S(=O) 2 O -< . E may be -C(=O)O -< .

[0030] Each R 3a< and R 3b< may be independently hydrogen or C 1 -C 4 alkyl. Each R 3a< and R 3b< may be independently hydrogen or -CH 3 . Each R 3a< and R 3b< may be hydrogen. Each R 3a< and R 3b< may be - CH 3 .

[0031] Each R 4c< and R 4d< may be independently selected from hydrogen and -CH 3 . Each R 4c< and R 4d< may be hydrogen.

[0032] Each R 5d< and R 5e< may be independently selected from hydrogen and -CH 3 . Each R 5d< and R 5e< may be hydrogen.

[0033] Each R 4c< , R 4d< , R 5d< , and R 5e< may be independently hydrogen or -CH 3 . Each R 4c< , R 4d< , R 5d< , and R 5e< may be hydrogen. Each R 4c< , R 4d< , R 5d< , and R 5e< may be -CH 3 .

[0034] Each R 6c< and R 6d< may be independently selected from hydrogen and -CH 3 . Each R 6c< and R 6d< may be hydrogen. Each R 6c< and R 6d< may be -CH 3 .

[0035] Each R 3c< and R 3d< may be independently selected from hydrogen and -CH 3 . Each R 3c< and R 3d< may be hydrogen.

[0036] Each R 3c< , R 3d< , R 6c< , and R 6d< may be independently hydrogen or -CH 3 . Each R 3c< , R 3d< , R 6c< , and R 6d< may be hydrogen. Each R 3c< , R 3d< , R 6c< , and R 6d< may be -CH 3 .

[0037] R 11a< may be hydrogen or -CH 3 . R 11a< may be hydrogen. R 11a< may be -CH 3 .

[0038] R 12a< may be hydrogen or -CH 3 . R 12a< may be hydrogen. R 12a< may be -CH 3 .

[0039] R 13a< may be hydrogen or -CH 3 . R 13a< may be hydrogen. R 13a< may be -CH 3 .

[0040] Each R 11a< , R 12a< , and R 13a< may be independently hydrogen or -CH 3 . Each R 11a< , R 12a< , and R 13a< may be hydrogen. Each R 11a< , R 12a< , and R 13a< may be -CH 3 .

[0041] Each R 11b< , R 11c< , R 12b< , R 12c< , R 13b< , and R 13c< may be hydrogen.

[0042] n may be 0, 1, 2, 3, 4, 5, or 6. n may be 0, 1, 2, 3, 4, or 5. n may be 0, 1, or 2. n may be 0. n may be 1. n may be 2. n may be 3. n may be 4. n may be 5.

[0043] s may be 1, 2, 3, or 4. s may be 1. s may be 2. s may be 3. s may be 4.

[0044] t may be 1, 2, 3, or 4. t may be 1. t may be 2. t may be 3. t may be 4.

[0045] p may be 1, 2, 3, or 4. p may be 1. p may be 2. p may be 3. p may be 4.

[0046] k may be 1, 2, 3, or 4. k may be 2, 3, or 4. k may be 2 or 3. k may be 1. k may be 2. k may be 3. k may be 4.

[0047] Each s, t, p, and k may be independently 1, 2, or 3. Each s, t, p, and k may be independently 1 or 2. Each s, t, p, and k may be independently 2 or 3.

[0048] A repeating unit of Formula (IX) may comprise a positively charged repeating unit of Formula (IX). A repeating unit of Formula (IX) may comprise a negatively charged repeating unit of Formula (IX). A copolymer comprising repeating units of Formula (VII), (VIII), and (IX) may comprise a positively charged repeating unit of Formula (IX) and a negatively charged repeating unit of Formula (IX). The ratio of positively charged repeating units of Formula (IX) and negatively charged repeating units of Formula (IX) in a copolymer comprising repeating units of Formula (VII), (VIII), and (IX) may be from about 10:1 to about 1:10. The ratio of positively charged repeating units of Formula (IX) and negatively charged repeating units of Formula (IX) in a copolymer comprising repeating units of Formula (VII), (VIII), and (IX) may be from about 5:1 to about 1:5. The ratio of positively charged repeating units of Formula (IX) and negatively charged repeating units of Formula (IX) in a copolymer comprising repeating units of Formula (VII), (VIII), and (IX) may be from about 2:1 to about 1:2. The ratio of positively charged repeating units of Formula (IX) and negatively charged repeating units of Formula (IX) in a copolymer comprising repeating units of Formula (VII), (VIII), and (IX) may be about 1:1.

[0049] A copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX) may comprise the following number of monomer units: [(Formula (VII))a(Formula (VIII))b(Formula (IX))c], wherein each number a, b, and c may be independently selected from 1 to 1000. Each number a, b, and c may be independently selected from 1 to 100.

[0050] a may be from 1 to 10. a may be from 5 to 10. a may be from 5 to 20. a may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 12, at least 15, or at least 20. a may be at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, at most 12, at most 15, or at most 20.

[0051] b may be from 5 to 75. b may be from 10 to 100. b may be from 20 to 250. b may be from 50 to 500. b may be from 100 to 1000. b may be at least 1, at least 5, at least 10, at least 25, at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, or at least 1000. b may be at most 1, at most 5, at most 10, at most 25, at most 50, at most 100, at most 200, at most 300, at most 400, at most 500, at most 600, at most 700, at most 800, at most 900, or at most 1000.

[0052] c may be from 5 to 75. c may befrom 10 to 100. c may be from 20 to 250. c may be from 50 to 500. c may be from 100 to 1000. c may be at least 1, at least 5, at least 10, at least 25, at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, or at least 1000. c may be at most 1, at most 5, at most 10, at most 25, at most 50, at most 100, at most 200, at most 300, at most 400, at most 500, at most 600, at most 700, at most 800, at most 900, or at most 1000.

[0053] The ratio of (b+c) to a may be from 1:1000 to 1000:1. The ratio of (b+c) to a may be from 1:100 to 100: 1. The ratio of (b+c) to a may be from 1: 10 to 10: 1. The ratio of (b+c) to a may be about 5:1, about 10: 1, about 20:1, about 30: 1, about 40: 1, about 50:1, about 75:1, about 100: 1, about 250: 1, about 500: 1, about 750:1, or about 1000: 1.

[0054] Different variables of a compound of Formula (VII), Formula (VIII), and Formula (IX) as described above are applicable to the corresponding Formulas, compositions, membranes, medical devices, etc. disclosed throughout the specification.Further Forms of Compounds

[0055] The copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX) may possess one or more stereocenters and each stereocenter may exist independently in either the R or S configuration. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms as well as the appropriate mixtures thereof. The compounds and methods provided herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof. Compounds described herein may be prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds / salts, separating the diastereomers and recovering the optically pure enantiomers. Resolution of enantiomers may be carried out using covalent diastereomeric derivatives of the compounds described herein. Diastereomers may be separated by separation / resolution techniques based upon differences in solubility. Separation of stereoisomers may be performed by chromatography or by the forming diastereomeric salts and separation by recrystallization, or chromatography, or any combination thereof. Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981. Stereoisomers may be obtained by stereoselective synthesis.

[0056] The compounds described herein may be labeled isotopically (e.g. with a radioisotope) or by another other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.

[0057] Compounds described herein include isotopically-labeled compounds, which are identical to those recited in the various formulae and structures presented herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the present compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, such as, for example, 2< H, 3< H, 13< C, 14< C, 15< N, 18< O, 17< O, 35< S, 18< F, 36< Cl. Isotopically-labeled compounds described herein, for example those into which radioactive isotopes such as 3< H and 14< C are incorporated, are useful in drug and / or substrate tissue distribution assays. Substitution with isotopes such as deuterium affords certain therapeutic advantages resulting from greater metabolic stability, such as, for example, increased in vivo half-life or reduced dosage requirements.

[0058] Compounds described herein might be formed as, and / or used as, salts. The type of salts, include, but are not limited to: (1) acid addition salts, formed by reacting the free base form of the compound with: inorganic acid, such as, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and metaphosphoric acid; or with an organic acid, such as, for example, acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, trifluoroacetic acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, butyric acid, phenylacetic acid, phenylbutyric acid, and valproic acid; (2) salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion (e.g. lithium, sodium, potassium), an alkaline earth ion (e.g. magnesium, or calcium), or an aluminum ion. In some cases, compounds described herein may coordinate with an organic base, such as, but not limited to, ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, dicyclohexylamine, tris(hydroxymethyl)methylamine. In other cases, compounds described herein may form salts with amino acids such as, but not limited to, arginine and lysine. Acceptable inorganic bases used to form salts with compounds that include an acidic proton, include, but are not limited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydroxide.

[0059] It should be understood that a reference to a salt includes the solvent addition forms, particularly solvates. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, such as water and ethanol. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein can be conveniently prepared or formed during the processes described herein. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein.Synthesis of Compounds

[0060] Compounds described herein are synthesized using standard synthetic techniques or using methods known in the art in combination with methods described herein.

[0061] Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques and pharmacology are employed.

[0062] Compounds are prepared using standard organic chemistry techniques such as those described in, for example, March's Advanced Organic Chemistry, 6th Edition, John Wiley and Sons, Inc. Alternative reaction conditions for the synthetic transformations described herein may be employed such as variation of solvent, reaction temperature, reaction time, as well as different chemical reagents and other reaction conditions. The starting materials are available from commercial sources or are readily prepared.

[0063] Suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, "Synthetic Organic Chemistry", John Wiley & Sons, Inc., New York; S. R. Sandler et al., "Organic Functional Group Preparations," 2nd Ed., Academic Press, New York, 1983; H. O. House, "Modern Synthetic Reactions", 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif. 1972; T. L. Gilchrist, "Heterocyclic Chemistry", 2nd Ed., John Wiley & Sons, New York, 1992; J. March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4th Ed., Wiley Interscience, New York, 1992. Additional suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, Fuhrhop, J. and Penzlin G. "Organic Synthesis: Concepts, Methods, Starting Materials", Second, Revised and Enlarged Edition (1994) John Wiley & Sons ISBN: 3 527-29074-5; Hoffman, R.V. "Organic Chemistry, An Intermediate Text" (1996) Oxford University Press, ISBN 0-19-509618-5; Larock, R. C. "Comprehensive Organic Transformations: A Guide to Functional Group Preparations" 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) "Modern Carbonyl Chemistry" (2000) Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. "Patai's 1992 Guide to the Chemistry of Functional Groups" (1992) Interscience ISBN: 0-471-93022-9; Solomons, T. W. G. "Organic Chemistry" 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., "Intermediate Organic Chemistry" 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471-57456-2; "Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia" (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; "Organic Reactions" (1942-2000) John Wiley & Sons, in over 55 volumes; and "Chemistry of Functional Groups" John Wiley & Sons, in 73 volumes.

[0064] In the reactions described, it may be necessary to protect reactive functional groups, for example hydroxy, amino, imino, thio or carboxy groups, where these are desired in the final product, in order to avoid their unwanted participation in reactions. A detailed description of techniques applicable to the creation of protecting groups and their removal are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994.

[0065] Compounds may be synthesized as described in the Examples section.Biofouling-Resistant Coatings

[0066] A biofouling-resistant coating may comprise the copolymer as described above, comprising: a) a repeating unit of Formula (VII): wherein each R 1a< and R 1b< is independently selected from hydrogen and halogen; each R 2a< and R 2b< is independently selected from halogen, -CN, and optionally substituted C 1 -C 6 fluoroalkyl; each A 1< and A 2< is independently selected from -C(=O)-, -S(=O)-, -S(=O) 2 -, and -S(=O)(=NR 3c< )-; each B 1< and B 2< is independently selected from -O- and -NR 3c< -; Z 1< is -(CR 6c< R 6d< ) s -; each R 4c< , R 4d< , R 5d< , R 5e< , R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 11a< , R 11b< , and R 11c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; and s is an integer selected from 1, 2, 3, 4, and 5; b) a repeating unit of Formula (VIII): wherein, A 3< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 3< is -O- or -NR 3c< -; D is -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; Z 2< is -(CR 6c< R 6d< ) t -; Z 3< is -(CR 6c< R 6d< ) p -; each R 3a< and R 3b< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted benzyl; each R 6c< and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 12a< , R 12b< , and R 12c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; t is an integer selected from 1, 2, 3, 4, or 5; p is an integer selected from 1, 2, 3, 4, or 5; and wherein the repeating unit of Formula (VIII) is charged or zwitterionic; and c) a repeating unit of Formula (IX): A 4< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 4< is -O- or -NR 3c< -; Z 4< is -(CR 6c< R 6d< ) k -; E is -CN, -OR 9a< , -NR 9a< R 9b< , -NR 9a< R 9b< R 9c+< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 6 fluoroalkyl, -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; each R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 9b< , R 9c< , R 13a< , R 13b< , and R 13c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; and k is an integer selected from 1, 2, 3, 4, or 5.

[0067] The repeating unit of Formula (IX) may be charged or zwitterionic.

[0068] Different variables of a compound of Formula (VII), Formula (VIII), and Formula (IX) are as described above.

[0069] Any combination of the groups described above or below for the various variables is contemplated herein.

[0070] The biofouling-resistant coating described herein may comprise one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX).

[0071] The biofouling-resistant coating comprising one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX) may be applied onto a surface of the medical device. The surface of the medical device may comprise a polymer. The polymer may be selected from polysiloxanes, polyurethanes, polyamides, polyimides, epoxy resins, polyesters, polyolefins, polysulfones, polycarbonates, polyvinylchloride, polyvinylidene difluoride, polyethers, polyether terpthalate, or a mixture thereof.Medical devices

[0072] The devices described herein are coated by one or more compounds described herein. The devices are medical devices and are coated by one or more compounds described herein. The coated device may reduce the potential for infection.

[0073] The device may comprise a polymer-based device. The polymer-based device may comprise a polyolefinic device. The polyolefinic device may comprise a device modified with polyethylene (PE), polypropylene (PP), polyamide (PA), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVdF), polyvinyl chloride (PVC), or a combination thereof. The device may comprise a microporous device or a nonwoven device. The device may comprise a carbon-based device comprising a moiety capable of binding with a copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX). The carbon-based device may comprise a polymer moiety. The carbon-based device may comprise a carbon-based polymer. The carbon-based device may comprise a polyolefin moiety. The polyolefin moiety may comprise a polyethylene (PE) moiety, a polypropylene (PP) moiety, a polyamide (PA) moiety, a polytetrafluoroethylene (PTFE) moiety, a polyvinylidene fluoride (PVdF) moiety, or a polyvinyl chloride (PVC) moiety.

[0074] The device may comprise a carbon-based device. The carbon-based device may comprise a carbon-based polymer. The carbon-based device may comprise a polyolefin moiety. The polyolefin moiety may comprise polyethylene moiety, polypropylene moiety, polyvinyl chloride moiety, polyvinylidene fluoride moiety, polytetrafluoroethylene moiety, polychlorotrifluoroethylene moiety, or polystyrene moiety. The carbon-based polymer may comprise polyamide moiety, polyurethane moiety, phenol-formaldehyde resin moiety, polycarbonate moiety, polychloroprene moiety, polyacrylonitrile moiety, polyimide moiety, or polyester moiety. The carbon-based polymer may comprises nylon. The carbon-based polymer may comprise polyethylene terephthalate.

[0075] The device may comprise a silicon-based device. The silicon-based device may comprise a silicon-based polymer moiety. The device may comprise a silicon-based device comprising a moiety capable of binding with a copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX). The silicon-based device may comprise a polymer moiety. The silicon-based device may comprise a siloxane polymer moiety, a sesquisiloxane polymer moiety, a siloxane-silarylene polymer moiety, a silalkylene polymer moiety, a polysilane moiety, a polysilylene moiety, or a polysilazane moiety.

[0076] The silicon-based device may comprise a siloxane polymer moiety. The silicon-based device may comprise silicone polymer. The silicon-based device may comprise a silicone-based device.

[0077] The device may comprise a carbon-based device or a silicon-based device.

[0078] A device described herein coated by a compound described herein may lead to a reduced potential for infection relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 10%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 20%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 30%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 40%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 50%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 60%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 70%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 80%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 90%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 95%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 99%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 99.5%, or more relative to a device not coated by the compound. In some instances, the reduced potential for infection is by about 99.9%, or more relative to a device not coated by the compound.

[0079] As already mentioned, a device described herein is a medical device. In some cases, a medical device described herein comprises a dental instrument or a medical instrument. In some instances, a medical device comprises an implant, an IV, a prosthesis, a suturing material, a valve, a stent, a catheter, a rod, a shunt, a scope, a contact lens, a tubing, a wiring, an electrode, a clip, a fastener, a syringe, a container, or a combination thereof. A medical device may comprise an implant. A medical device may comprise an IV. A medical device may comprise a prosthesis. A medical device may comprise a suturing material. A medical device may comprise a valve. A medical device may comprise a stent. A medical device may comprise a catheter. A medical device may comprise a rod. A medical device may comprise a shunt. A medical device may comprise a scope. A medical device may comprise a contact lens. A medical device may comprise a tubing. A medical device may comprise a wiring. A medical device may comprise an electrode. A medical device may comprise a clip. A medical device may comprise a fastener. A medical device may comprise a syringe. A medical device may comprise a container.

[0080] A compound described herein may be coated onto a medical device. In some instances, a compound described herein is coated onto a medical device to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a dental instrument or a medical instrument to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto an implant, an IV, a prosthesis, a suturing material, a valve, a stent, a catheter, a rod, a shunt, a scope, a contact lens, a tubing, a wiring, an electrode, a clip, a fastener, a syringe, a container, or a combination thereof to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0081] In some cases, a medical device described herein comprises a catheter. In some cases, a catheter comprises an indwelling catheter. In some instances, a catheter comprises a permcath. In some instances, a catheter comprises a uretic catheter or a Foley catheter.

[0082] In some instances, a compound described herein is coated onto a catheter to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto an indwelling catheter to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a permcath to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a uretic catheter to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a Foley catheter to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0083] In some instances, a medical device described herein comprises an implant. In some instances, an implant comprises a dental implant or an orthopedic implant. In some cases, a medical device described herein comprises a dental implant. In other cases, a medical device described herein comprises an orthopedic implant.

[0084] In some instances, a compound described herein is coated onto an implant to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a dental implant to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto an orthopedic implant to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0085] In some instances, a medical device described herein comprises an IV. In some instances, a compound described herein is coated onto an IV to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0086] In some instances, a medical device described herein comprises a prosthesis. In some cases, a prosthesis comprises an artificial bone, an artificial joint, an artificial organ, or a denture. In some cases, an artificial organ comprises an artificial pancreas, an artificial heart, an artificial limb, or a heart valve. In some instances, a medical device described herein comprises an artificial bone, an artificial joint, an artificial organ or a denture. In some instances, a medical device described herein comprises an artificial pancreas, an artificial heart, an artificial limb, or a heart valve.

[0087] In some instances, a compound described herein is coated onto prosthesis to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto an artificial bone, an artificial joint, an artificial organ, or a denture to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto an artificial pancreas, an artificial heart, an artificial limb, or a heart valve to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0088] In some instances, a medical device described herein comprises a stent. In some instances, a stent is a small expandable tube used to the passageway of a blood vessel or duct remains open. In some cases, a stent comprises a coronary stent, a vascular stent, or a biliary stent. In some instances, a coronary stent is also referred to as a cardiac stent or a heart stent. In some instances, a medical device described herein comprises a coronary stent, a vascular stent, or a biliary stent.

[0089] In some instances, a compound described herein is coated onto stent to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a coronary stent, a vascular stent, or a biliary stent to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0090] In some instances, a medical device described herein comprises shunt. In some instances, a shunt is a hole or a small passage which allows fluid movement from one part of a body to another. In some instances, a shunt differs from a stent in that a shunt connects two previously unconnected portions. In some instances, a shunt is an acquired shunt. In some cases, a shunt comprises a cardiac shunt, a cerebral shunt, a lumbar-peritoneal shunt, a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt (PSS), a portacaval shunt, or a vesico-amniotic shunt. In some cases, a cardiac shunt comprises a right-to-left, left-to-right, or bidirectional shunt. In some cases, a cerebral shunt comprises drainage of excess cerebrospinal fluid from the brain into the chest or abdomen cavity. In some cases, a lumbar-peritoneal shunt comprises channeling cerebrospinal fluid from the lumbar thecal sac into the peritoneal cavity. In some instances, a peritoneovenous shunt (also referred to as Denver shunt) drains peritoneal fluid from the peritoneum into the veins. In some cases, a portosystemic shunt (PSS) is a liver shunt which allows bypass of the liver by the circulatory system. In some cases, a portacaval shunt connects the portal vein with the inferior vena cava, for treatment of high blood pressure in the liver. In some cases, a vesico-amniotic shunt is for drainage of excess fluid in a fetus bladder into the surrounding area. In some cases, a medical device described herein comprises a cardiac shunt, a cerebral shunt, a lumbar-peritoneal shunt, a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt (PSS), a portacaval shunt, or a vesico-amniotic shunt.

[0091] In some instances, a compound described herein is coated onto shunt to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto a cardiac shunt, a cerebral shunt, a lumbar-peritoneal shunt, a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt (PSS), a portacaval shunt, or a vesico-amniotic shunt to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0092] In some instances, a medical device described herein comprises a scope. In some cases, a scope is a medical instrument used in an image-guided surgery. In some cases, a scope comprises endoscope or laparoscope. Endoscopy is a medical procedure for examining the GI tract with the aid of an endoscope. In some cases, endoscopy further comprises sigmoidoscopy and colonoscopy. Laparoscopy is a diagnostic procedure for examining internal organs utilizing a laparoscope. In some instances, a medical device described herein comprises a scope used in endoscopy. In other instances, a medical device described herein comprises a scope used in laparoscopy.

[0093] In some instances, a compound described herein is coated onto scope to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto endoscope to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto laparoscope to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0094] In some instances, a medical device described herein comprises suturing material, valve, rod, tubing, wiring, electrode, clip, fastener, or a combination thereof. In some instances, a compound described herein is coated onto suturing material, valve, rod, tubing, wiring, electrode, clip, fastener, or a combination thereof to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0095] In some instances, a medical device described herein comprises a syringe. In some cases, a syringe further comprises a needle. In some instances, a compound described herein is coated onto a syringe to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0096] In some instances, a medical device described herein comprises a container, such as for storage of one or more medical devices. In some instances, a compound described herein is coated onto a container to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0097] In some instances, a medical device described herein comprises a bandage or a patch. In some cases, a medical device described herein comprises a bandage. In other cases, a medical device described herein comprises a patch.

[0098] In some instances, a compound described herein is coated onto a bandage to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm). In some instances, a compound described herein is coated onto patch to prevent and / or reduce biofouling (e.g., microfouling such as bacteria adhesion or biofilm).

[0099] A medical device described herein is coated by a copolymer as described above, comprising: a) a repeating unit of Formula (VII): wherein each R 1a< and R 1b< is independently selected from hydrogen and halogen; each R 2a< and R 2b< is independently selected from halogen, -CN, and optionally substituted C 1 -C 6 fluoroalkyl; each A 1< and A 2< is independently selected from -C(=O)-, -S(=O)-, -S(=O) 2 -, and -S(=O)(=NR 3c< )-; each B 1< and B 2< is independently selected from -O- and -NR 3c< -; Z 1< is -(CR 6c< R 6d< ) s -; each R 4c< , R 4d< , R 5d< , R 5e< , R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 11a< , R 11b< , and R 11c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; and s is an integer selected from 1, 2, 3, 4, and 5; b) a repeating unit of Formula (VIII): wherein, A 3< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 3< is -O- or -NR 3c< -; D is -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; Z 2< is -(CR 6c< R 6d< ) t -; Z 3< is -(CR 6c< R 6d< ) p -; each R 3a< and R 3b< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted benzyl; each R 6c< and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 12a< , R 12b< , and R 12c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; t is an integer selected from 1, 2, 3, 4, or 5; p is an integer selected from 1, 2, 3, 4, or 5; and wherein the repeating unit of Formula (VIII) is charged or zwitterionic; and c) a repeating unit of Formula (IX): A 4< is -C(=O)-, -S(=O)-, -S(=O) 2 -, or -S(=O)(=NR 3c< )-; B 4< is -O- or -NR 3c< -; Z 4< is -(CR 6c< R 6d< ) k -; E is -CN, -OR 9a< , -NR 9a< R 9b< , -NR 9a< R 9b< R 9c+< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 6 fluoroalkyl, -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , or -C(=O)OR 9a< ; each R 6c< , and R 6d< is independently selected from hydrogen, halogen, -CN, -OR 9a< , optionally substituted C 1 -C 4 alkyl, optionally substituted C 1 -C 4 fluoroalkyl, optionally substituted C 2 -C 6 alkenyl, -NR 3c< R 3d< , -S(=O) 2 O -< , -S(=O) 2 OR 9a< , -C(=O)O -< , and -C(=O)OR 9a< ; each R 3c< and R 3d< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, -X-optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O) 2 -; each R 9a< , R 9b< , R 9c< , R 13a< , R 13b< , and R 13c< is independently selected from hydrogen, optionally substituted C 1 -C 4 alkyl, and optionally substituted aryl; and k is an integer selected from 1, 2, 3, 4, or 5.

[0100] The repeating unit of Formula (IX) may be charged or zwitterionic.

[0101] Different variables of a compound of Formula (VII), Formula (VIII), and Formula (IX) are as described above.

[0102] A medical device described herein is a biofouling-resistant medical device, wherein a surface of the medical device is coated with one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX).

[0103] The phenyl azide-based copolymer may have a number-average molecular weight of at least about 10,000, about 20,000, about 30,000, about 40,000, about 50,000, about 60,000, about 70,000, about 80,000, about 90,000, about 100,000, about 110,000, about 120,000, about 130,000, about 140,000, about 150,000, about 160,000, about 170,000, about 180,000, about 190,000, or about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of no more than about 10,000, about 20,000, about 30,000, about 40,000, about 50,000, about 60,000, about 70,000, about 80,000, about 90,000, about 100,000, about 110,000, about 120,000, about 130,000, about 140,000, about 150,000, about 160,000, about 170,000, about 180,000, about 190,000, or about 200,000.

[0104] The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 40,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 60,000. The phenyl azide-based copolymer have a number-average molecular weight of between about 10,000 and about 80,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 10,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 40,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 60,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 80,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 60,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 80,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 40,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 80,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 60,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 80,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 100,000 and about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 100,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 100,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 100,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 100,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 120,000 and about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 120,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 120,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 120,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 140,000 and about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 140,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 140,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 160,000 and about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 160,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 200,000 and about 250,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 10,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 40,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 60,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 80,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 100,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 120,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 140,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 160,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 200,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 250,000.

[0105] A surface of the medical device described herein may be coated with one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX) described herein having a number-average molecular weight of between about 10,000 and about 250,000, e.g. between about 14,000 and about 21,000.

[0106] The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 15,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 16,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 17,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 18,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 14,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 16,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 17,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 18,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 15,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 16,000 and about 17,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 16,000 and about 18,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 16,000 and about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 16,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 16,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 17,000 and about 18,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 17,000 and about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 17,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 17,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 18,000 and about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 18,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 18,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 19,000 and about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 19,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of between about 20,000 and about 21,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 14,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 15,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 16,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 17,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 18,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 19,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 20,000. The phenyl azide-based copolymer may have a number-average molecular weight of about 21,000.

[0107] A surface of the medical device described herein may be coated with one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX) described herein having a polydispersity index (PDI) of between about 1 and 1.5.

[0108] The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of at least about 1, about 1.1, about 1.2, about 1.3, about 1.4, or about 1.5. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of no more than about 1, about 1.1, about 1.2, about 1.3, about 1.4, or about 1.5.

[0109] The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1 and 1.1. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1 and 1.2. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1 and 1.3. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1 and 1.4. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1 and 1.5. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.1 and 1.2. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.1 and 1.3. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.1 and 1.4. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.1 and 1.5. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.2 and 1.3. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.2 and 1.4. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.2 and 1.5. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.3 and 1.4. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.3 and 1.5. The surface of the medical device may be coated with a phenyl azide-based copolymer having a polydispersity index (PDI) of between about 1.4 and 1.5. The PDI may be about 1. The PDI may be about 1.1. The PDI may be about 1.2. The PDI may be about 1.3. The PDI may be about 1.4. The PDI may be about 1.5. The PDI may be about 1.11. The PDI may be about 1.12. The PDI may be about 1.13. The PDI may be about 1.14. The PDI may be about 1.15. The PDI may be about 1.16. The PDI may be about 1.17. The PDI may be about 1.18. The PDI may be about 1.19. The PDI may be about 1.21. The PDI may be about 1.22. The PDI may be about 1.23. The PDI may be about 1.24. The PDI may be about 1.25.

[0110] The medical device may comprise a dental instrument or a medical instrument. The medical device may comprise an implant, an IV, a prosthesis, a suturing material, a valve, a stent, a catheter, a rod, a shunt, a scope, a contact lens, a tubing, a wiring, an electrode, a clip, a fastener, a syringe, a container, or a combination thereof. The medical device may be a contact lens. The medical device may be a catheter. The catheter may be an indwelling catheter. The catheter may comprise a uretic catheter or a Foley catheter. The medical device may be a scope. The scope may comprise a scope utilized in an image-guided surgery. The scope may comprise a scope utilized in endoscopy or laparoscopy.

[0111] The medical device may comprise auditory prostheses, artificial larynx, dental implants, mammary implants, penile implants, cranio / facial tendons, tendons, ligaments, menisci, or disks. The medical device may comprise artificial bones, artificial joints, or artificial organs. The artificial organs may comprise artificial pancreas, artificial hearts, artificial limbs, or heart valves. The medical device may comprise a bandage or a patch.

[0112] The copolymer may comprise zwitterionic copolymer. The zwitterionic copolymer may comprise polysulfobetaine.

[0113] The biofouling may be produced by a bacterium, a virus, and / or a fungus.

[0114] A compound described herein may be coated onto a medical device. In some cases, a compound described herein is coated directly onto a medical device. In other instances, a compound described herein is coated indirectly onto a medical device. In some cases, the coating comprises dip-coating. In other cases, the coating comprises spray coating.

[0115] A compound described herein may be coated onto a medical device to reduce the formation of biofouling. In some cases, the formation of biofouling is reduced by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 10%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 20%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 30%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 40%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 50%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 60%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 70%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 80%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 90%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 95%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 99%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 99.5%, or more relative to a device not coated with the compound. In some instances, the formation of biofouling is reduced by about 99.9%, or more relative to a device not coated with the compound.Methods of Making

[0116] A method of making a biofouling-resistant medical device as described herein comprises: a) contacting a surface of a device with a mixture (e.g., a solution) comprising a copolymer as described above; and b) treating the surface of the device of step a) with a heat source for a time sufficient to undergo thermografting of the copolymer onto the surface of the device, thereby making the biofouling-resistant device.

[0117] The method may comprise one-step grafting reaction that modifies the surface of a device.

[0118] The device is a medical device as described herein.

[0119] The time sufficient to undergo thermografting may be 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 18 hours, or 24 hours. The time sufficient to undergo thermografting may be at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 45 minutes, at least 1 hour, at least 1.5 hours, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 9 hours, at least 12 hours, or at least 18 hours. The time sufficient to undergo thermografting may be at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 6 minutes, at most 7 minutes, at most 8 minutes, at most 9 minutes, at most 10 minutes, at most 15 minutes, at most 20 minutes, at most 25 minutes, at most 30 minutes, at most 45 minutes, at most 1 hour, at most 1.5 hours, at most 2 hours, at most 3 hours, at most 4 hours, at most 5 hours, at most 6 hours, at most 9 hours, at most 12 hours, at most 18 hours, or at most 24 hours.

[0120] The heat source may provide a grafting temperature between 40 and 380 degree Celsius (°C). The heat source may provide a grafting temperature between 40 °C and 360 °C. The heat source may provide a grafting temperature between 60 °C and 320 °C. The heat source may provide a grafting temperature between 80 °C and 260 °C. The heat source may provide a grafting temperature between 100 °C and 220 °C. The heat source may provide a grafting temperature between 120 °C and 220 °C. The heat source may provide a grafting temperature between 40 °C and 60 °C, between 60 °C and 80 °C, between 80 °C and 100 °C, between 100 °C and 120 °C, between 120 °C and 140 °C, between 140 °C and 160 °C, between 160 °C and 180 °C, between 180 °C and 200 °C, between 200 °C and 220 °C, between 220 °C and 240 °C, between 240 °C and 260 °C, between 260 °C and 280 °C, between 280 °C and 300 °C, between 300 °C and 320 °C, between 320 °C and 340 °C, or between 340 °C and 360 °C. The heat source may provide a grafting temperature between 60 °C and 80 °C, between 80 °C and 100 °C, between 100 °C and 120 °C, between 120 °C and 140 °C, between 140 °C and 160 °C, between 160 °C and 180 °C, between 180 °C and 200 °C, between 200 °C and 220 °C, or between 220 °C and 240 °C. The heat source may provide a grafting temperature of 60 °C, 80 °C, 100°C, 120 °C, 140 °C, 160 °C, 180 °C, 200 °C, 220 °C, 240 °C, 260 °C, 280 °C, or 300 °C. The heat source may provide a grafting temperature of 60 °C, 80 °C, 100°C, 120 °C, 140 °C, 160 °C, 180°C, 200 °C, or 220 °C. The heat source may provide a grafting temperature of at least 60 °C, at least 80 °C, at least 100 °C, at least 120 °C, at least 140 °C, at least 160 °C, at least 180 °C, at least 200 °C, at least 220 °C, at least 240 °C , at least 260 °C, or at least 280 °C. The heat source may provide a grafting temperature of at most 80 °C, at most 100 °C, at most 120 °C, at most 140 °C, at most 160 °C, at most 180 °C, at most 200 °C, at most 220 °C, at most 240 °C, at most 260 °C, at most 280 °C, or at most 300 °C.

[0121] The mixture of step a) may be an aqueous solution, an aqueous colloid, or an aqueous suspension. The mixture of step a) may be a non-aqueous solution, an aqueous colloid, or an aqueous suspension.

[0122] The mixture comprising a charged or zwitterion copolymer may have a concentration of the charged or zwitterion copolymer in the mixture between 1 mg / mL and 30 mg / mL.

[0123] The concentration of the charged or zwitterion copolymer in the mixture may be between 0.1 mg / mL and 100 mg / mL, 0.5 mg / mL and 50 mg / mL, 1 mg / mL and 25 mg / mL, between 1 mg / mL and 20 mg / mL, between 1 mg / mL and 15 mg / mL, between 1 mg / mL and 10 mg / mL, between 1 mg / mL and 5 mg / mL, between 5 mg / mL and 30 mg / mL, between 5 mg / mL and 25 mg / mL, between 5 mg / mL and 20 mg / mL, between 5 mg / mL and 15 mg / mL, between 5 mg / mL and 10 mg / mL, between 10 mg / mL and 30 mg / mL, between 10 mg / mL and 25 mg / mL, between 10 mg / mL and 20 mg / mL, between 10 mg / mL and 15 mg / mL, between 15 mg / mL and 30 mg / mL, between 15 mg / mL and 25 mg / mL, between 15 mg / mL and 20 mg / mL, between 20 mg / mL and 30 mg / mL, or between 20 mg / mL and 25 mg / mL. The concentration of the charged or zwitterion copolymer in the mixture may be between 25 mg / mL and 30 mg / mL, between 30 mg / mL and 35 mg / mL, between 35 mg / mL and 40 mg / mL, between 40 mg / mL and 45 mg / mL, between 45 mg / mL and 50 mg / mL, between 50 mg / mL and 55 mg / mL, between 55 mg / mL and 60 mg / mL, between 60 mg / mL and 65 mg / mL, between 65 mg / mL and 70 mg / mL, between 70 mg / mL and 75 mg / mL, between 75 mg / mL and 80 mg / mL, between 80 mg / mL and 85 mg / mL, between 85 mg / mL and 90 mg / mL, between 90 mg / mL and 95 mg / mL, or between 95 mg / mL and 100 mg / mL.

[0124] The concentration of the charged or zwitterion copolymer in the mixture may be about 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL, 25 mg / mL, 26 mg / mL, 27 mg / mL, 28 mg / mL, 29 mg / mL, or 30 mg / mL. The concentration of the charged or zwitterion copolymer in the mixture may be about 31 mg / mL, 32 mg / mL, 33 mg / mL, 34 mg / mL, 35 mg / mL, 36 mg / mL, 37 mg / mL, 38 mg / mL, 39 mg / mL, 40 mg / mL, 41 mg / mL, 42 mg / mL, 43 mg / mL, 44 mg / mL, 45 mg / mL, 46 mg / mL, 47 mg / mL, 48 mg / mL, 49 mg / mL, 50 mg / mL, 51 mg / mL, 52 mg / mL, 53 mg / mL, 54 mg / mL, 55 mg / mL, 56 mg / mL, 57 mg / mL, 58 mg / mL, 59 mg / mL, or 60 mg / mL.

[0125] The concentration of the charged or zwitterion copolymer may be between 0.01 to 10 mg per square centimeter of the medical device. The concentration of the charged or zwitterion copolymer may be between 0.1 to 1 mg per square centimeter of the medical device. The concentration of the charged or zwitterion copolymer may be between 0.01 to 0.05, between 0.1 to 0.2, between 0.2 to 0.3, between 0.3 to 0.4, between 0.4 to 0.5, between 0.5 to 0.6, between 0.6 to 0.7, between 0.7 to 0.8, between 0.8 to 0.9, between 0.9 to 1, between 1 to 2, between 2 to 2, between 3 to 2, between 4 to 2, between 5 to 2, between 6 to 2, between 7 to 2, between 8 to 2, or between 9 to 10 per square centimeter of the medical device.

[0126] The medical device may comprise a polymer-based device. The polymer-based device may comprise a polyolefinic device. The polyolefinic device may comprise a device modified with polyethylene (PE), polypropylene (PP), polyamide (PA), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVdF), polyvinyl chloride (PVC), or a combination thereof. The medical device may comprise a microporous device or a nonwoven device. The medical device may comprise a carbon-based device comprising a moiety capable of binding with a copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX). The carbon-based device may comprise a polymer moiety. The carbon-based device may comprise a carbon-based polymer. The carbon-based device may comprise a polyolefin moiety. The polyolefin moiety may comprise a polyethylene (PE) moiety, a polypropylene (PP) moiety, a polyamide (PA) moiety, a polytetrafluoroethylene (PTFE) moiety, a polyvinylidene fluoride (PVdF) moiety, or a polyvinyl chloride (PVC) moiety.

[0127] The medical device may comprise a carbon-based device. The carbon-based device may comprise a carbon-based polymer. The carbon-based device may comprise a polyolefin moiety. The polyolefin moiety may comprise polyethylene moiety, polypropylene moiety, polyvinyl chloride moiety, polyvinylidene fluoride moiety, polytetrafluoroethylene moiety, polychlorotrifluoroethylene moiety, or polystyrene moiety. The carbon-based polymer may comprise polyamide moiety, polyurethane moiety, phenol-formaldehyde resin moiety, polycarbonate moiety, polychloroprene moiety, polyacrylonitrile moiety, polyimide moiety, or polyester moiety. The carbon-based polymer may comprise nylon. The carbon-based polymer may comprise polyethylene terephthalate.

[0128] The medical device may comprise a silicon-based device. The silicon-based device may comprise a silicon-based polymer moiety. The medical device may comprise a silicon-based device comprising a moiety capable of binding with a copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX). The silicon-based device may comprise a polymer moiety. The silicon-based device may comprise a siloxane polymer moiety, a sesquisiloxane polymer moiety, a siloxane-silarylene polymer moiety, a silalkylene polymer moiety, a polysilane moiety, a polysilylene moiety, or a polysilazane moiety.

[0129] The silicon-based device may comprise a siloxane polymer moiety. The silicon-based device may comprise a silicone polymer.

[0130] The medical device may comprises a carbon-based device or a silicon-based device.

[0131] The copolymer may comprise zwitterionic copolymer. The zwitterionic copolymer may comprise polysulfobetaine.

[0132] The biofouling of the biofouling-resistant medical device described herein may be produced by a bacterium, a virus, and / or a fungus.Properties of Biofouling-Resistant Coatings

[0133] Biofouling-resistant coatings disclosed herein may have various properties that provide the superior function of the medical devices, including excellent flux, improved hydrophilicity, improved resistance to fouling, tunable surface charge properties, higher thermal stability, higher chemical stability, higher solvent stability, or a combination thereof. It is also understood that the coatings disclosed herein have other properties.

[0134] A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 70°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 65°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 60°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 55°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 50°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 45°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 40°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 35°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 30°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 25°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 20°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 15°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 10°. A biofouling-resistant coating disclosed herein may have a water receding angle of less than about 5°. A biofouling-resistant coating disclosed herein may have a water receding angle of about 0°. The medical devices provided herein, coated by one or more biofouling-resistant coatings described herein may have a high resistance of fouling.

[0135] A biofouling-resistant coating disclosed herein may exhibit an improvement in at least one property selected from resistance to fouling, hydrophilicity, surface charge, salt rejection, and roughness. A biofouling-resistant coating disclosed herein may demonstrate an improvement in at least one property selected from resistance to fouling, salt rejection, and hydrophilicity. A biofouling-resistant coating disclosed herein may demonstrate an improvement in resistance to fouling. A biofouling-resistant coating disclosed herein may demonstrate an improvement in hydrophilicity. A biofouling-resistant coating disclosed herein may demonstrate an improvement in surface charge. A biofouling-resistant coating disclosed herein may demonstrate an improvement in roughness. A biofouling-resistant coating disclosed herein may demonstrate reduced surface roughness. A biofouling-resistant coating disclosed herein may demonstrate an improvement in salt rejection.

[0136] A biofouling-resistant coating disclosed herein comprising one or more copolymers comprising repeating units of Formula (VII), (VIII), and (IX) described herein may prevent and / or reduce biofouling. In some instances, biofouling comprises microfouling or macrofouling. Microfouling comprises formation of microorganism adhesion (e.g., bacteria adhesion) and / or biofilm. Biofilm is a group of microorganism which adheres to a surface. In some instances, the adhered microorganisms are further embedded in a self-produced matrix of extracellular polymeric substance, which comprises a polymeric conglomeration of extracellular DNA, protein, and polysaccharides. Macrofouling comprises attachment of larger organism. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacterial adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm. A biofouling-resistant coating disclosed herein may prevent and / or reduce macrofouling.Microfouling

[0137] In some instances, microfouling is formed by bacteria or fungi. In some instances, microfouling is formed by bacteria. In some instances, a bacterium is a gram-positive bacterium or a gram-negative bacterium. In some cases, a bacterium is a marine bacterium.

[0138] In some cases, microfouling is formed by a gram-positive bacterium. Exemplary gram-positive bacteria include, but are not limited to, bacteria from the genus Actinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. In some instances, a gram-positive bacterium comprises Actinomyces spp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile, Clostridium spp., Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcus pyogenes.

[0139] In some instances, microfouling is formed by a gram-positive bacterium from the genus Actinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. In some instances, microfouling is formed by a gram-positive bacterium: Actinomyces spp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile, Clostridium spp., Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcus pyogenes.

[0140] In some instances, a biofouling-resistant coating disclosed herein is resistant to fouling. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling on one or more of its surfaces. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a gram-positive bacterium from the genus Actinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a gram-positive bacterium: Actinomyces spp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile, Clostridium spp., Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcus pyogenes.

[0141] In some cases, microfouling comprises bacteria adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by a gram-positive bacterium from the genus Actinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. A biofouling-resistant coating disclosed herein coated onto a material may prevent and / or reduce bacteria adhesion formed by a gram-positive bacterium: Actinomyces spp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile, Clostridium spp., Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcus pyogenes.

[0142] In some cases, microfouling comprises biofilm. A biofouling-resistant coating disclosed herein coated onto a material may prevent and / or reduce biofilm. A biofouling-resistant coating disclosed herein coated onto a material may prevent and / or reduce biofilm formed by a gram-positive bacterium from the genus Actinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. A biofouling-resistant coating disclosed herein coated onto a material may prevent and / or reduce biofilm formed by a gram-positive bacterium: Actinomyces spp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile, Clostridium spp., Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcus pyogenes.

[0143] In some cases, microfouling is formed by a gram-negative bacterium. Exemplary gram-negative bacteria include, but are not limited to, bacteria from the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. In some instances, a gram-negative bacterium comprises Alteromonas spp., Aeromonas spp., Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonella enterica, or Vibrio Cholerae.

[0144] In some instances, microfouling is formed by a gram-negative bacterium from the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. In some instances, microfouling is formed by a gram-negative bacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonella enterica, or Vibrio Cholerae.

[0145] A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a gram-negative bacterium from the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a gram-negative bacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonella enterica, or Vibrio Cholerae.

[0146] In some instances, microfouling comprises bacteria adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by a gram-negative bacterium from the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by a gram-negative bacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonella enterica, or Vibrio Cholerae.

[0147] In some instances, microfouling comprises biofilm. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by a gram-negative bacterium from the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by a gram-negative bacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonella enterica, or Vibrio Cholerae.

[0148] In some cases, microfouling is formed by a marine bacterium. In some instances, a marine bacterium comprises Pseudoalteromonas spp. or Shewanella spp. In some cases, microfouling is formed by Pseudoalteromonas spp. or Shewanella spp.

[0149] A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a marine bacterium. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by Pseudoalteromonas spp. or Shewanella spp.

[0150] In some instances, microfouling comprises bacteria adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by a marine bacterium. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by Pseudoalteromonas spp. or Shewanella spp.

[0151] In some instances, microfouling comprises biofilm. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by a marine bacterium. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by Pseudoalteromonas spp. or Shewanella spp.

[0152] In some instances, microfouling is formed by a fungus. Exemplary fungus includes, but is not limited to, Candida albicans, Candida glabrata, Candida rugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconis resinae. In some cases, microfouling is formed by Candida albicans, Candida glabrata, Candida rugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconis resinae.

[0153] A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by a fungus. A biofouling-resistant coating disclosed herein may prevent and / or reduce microfouling formed by Candida albicans, Candida glabrata, Candida rugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconis resinae.

[0154] In some instances, microfouling comprises bacteria adhesion. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by a fungus. A biofouling-resistant coating disclosed herein may prevent and / or reduce bacteria adhesion formed by Candida albicans, Candida glabrata, Candida rugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconis resinae.

[0155] In some instances, microfouling comprises biofilm. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by a fungus. A biofouling-resistant coating disclosed herein may prevent and / or reduce biofilm formed by Candida albicans, Candida glabrata, Candida rugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconis resinae.Macrofouling

[0156] In some instances, macrofouling comprises calcareous fouling organism or non-calcareous fouling organism. A calcareous fouling organism is an organism with a hard body. In some cases, calcareous fouling organisms comprise barnacle, bryozoan, mollusk, polychaete, tube worm, or zebra mussel. A non-calcareous fouling organism comprises a soft body. Non-calcareous fouling organism comprises seaweed, hydroids, or algae.

[0157] In some instances, macrofouling is formed by a calcareous fouling organism. In some cases, macrofouling is formed by barnacle, bryozoan, mollusk, polychaete, tube worm, or zebra mussel.

[0158] A biofouling-resistant coating disclosed herein may prevent and / or reduce macrofouling formed by a calcareous fouling organism. A biofouling-resistant coating disclosed herein may prevent and / or reduce macrofouling formed by barnacle, bryozoan, mollusk, polychaete, tube worm, or zebra mussel.

[0159] In some cases, macrofouling is formed by a non-calcareous fouling organism. In some cases, macrofouling is formed by seaweed, hydroids, or algae.

[0160] A biofouling-resistant coating may prevent and / or reduce macrofouling formed by a non-calcareous fouling organism. A biofouling-resistant coating disclosed herein may prevent and / or reduce macrofouling formed by seaweed, hydroids, or algae.

[0161] A biofouling-resistant coating disclosed herein may reduce the formation of biofouling on its surface. In some cases, the formation of biofouling on a surface of a medical device modified with a copolymer comprising a repeating unit of Formula (VII), (VIII), and (IX) is reduced by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling relative to the unmodified surface of a medical device is determined by comparing the amount of biofouling following a period of time of storage, use, and / or testing of the medical device(s). For example, the medical devices may be tested by exposing them to conditions conducive of biofouling formation (e.g., in vitro biofouling testing techniques known and practiced in the art). In some instances, the formation of biofouling is reduced by about 10%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 20%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 30%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 40%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 50%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 60%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 70%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 80%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 90%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 95%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 99%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 99.5%, or more relative to the unmodified surface of a medical device. In some instances, the formation of biofouling is reduced by about 99.9%, or more relative to the unmodified surface of a medical device.

[0162] A biofouling-resistant coating disclosed herein may be further coated with an additional agent. In some instances, the additional agent is an antimicrobial agent. Exemplary antimicrobial agent comprises quaternary ammonium salts or tertiary amines. In some instances, the additional agent is a chemical disinfectant. Exemplary chemical disinfectant comprises sodium hypochlorite, sodium hydroxide, and benzalkonium chloride.Definitions

[0163] As used herein, nomenclature for compounds, including organic compounds, can be given using common names, IUPAC, IUBMB, or CAS recommendations for nomenclature. When one or more stereochemical features are present, Cahn-Ingold-Prelog rules for stereochemistry can be employed to designate stereochemical priority, E / Z specification, and the like. One of skill in the art can readily ascertain the structure of a compound if given a name, either by systemic reduction of the compound structure using naming conventions, or by commercially available software, such as CHEMDRAW ™< (Cambridgesoft Corporation, U.S.A.).

[0164] As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component," "a polymer," or "a particle" includes mixtures of two or more such components, polymers, or particles, and the like.

[0165] Ranges can be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. The term "about" may include an amount that would be expected to be within experimental error. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "10" is disclosed the "less than or equal to 10" as well as "greater than or equal to 10" is also disclosed. It is also understood that throughout the specification, data is provided in a number of different formats and that this data represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point "10" and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0166] References in the specification and appended claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

[0167] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included.

[0168] As used herein, the terms "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0169] As used herein, the terms "effective amount" and "amount effective" refer to an amount that is sufficient to achieve the desired result or to have an effect on an undesired condition.

[0170] The term "stable", as used herein, refers to compositions that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain aspects, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0171] As used herein, the term "polymer" refers to a relatively high molecular weight organic compound, natural or synthetic, whose structure can be represented by a repeated small unit, the monomer (e.g., polyethylene, rubber, cellulose). Synthetic polymers are typically formed by addition or condensation polymerization of monomers. Unless indicated otherwise, polymer molecular weights are given in Daltons.

[0172] As used herein, the term "homopolymer" refers to a polymer formed from a single type of repeating unit (monomer residue).

[0173] As used herein, the term "copolymer" refers to a polymer formed from two or more different repeating units (monomer residues). By way of example and without limitation, a copolymer can be an alternating copolymer, a random copolymer, a block copolymer, or a graft copolymer. It is also contemplated that, in certain aspects, various block segments of a block copolymer can themselves comprise copolymers. The terms "copolymer" and "compound" may be used interchangeably throughout the specification.

[0174] As used herein, the term "oligomer" refers to a relatively low molecular weight polymer in which the number of repeating units is between two and ten, for example, from two to eight, from two to six, or form two to four. In one aspect, a collection of oligomers can have an average number of repeating units of from about two to about ten, for example, from about two to about eight, from about two to about six, or form about two to about four.

[0175] As used herein, the term "cross-linked polymer" refers to a polymer having bonds linking one polymer chain to another.

[0176] As used herein, the term "porogen composition" or "porogen(s)" refers to any structured material that can be used to create a porous material.

[0177] "Oxo" refers to the =O substituent.

[0178] "Benzyl" refers to the -CH 2 (C 6 H 5 ) substituent.

[0179] "Alkyl" refers to a straight or branched hydrocarbon chain radical, having from one to twenty carbon atoms, and which is attached to the rest of the molecule by a single bond. An alkyl comprising up to 10 carbon atoms is referred to as a C 1 -C 10 alkyl, likewise, for example, an alkyl comprising up to 6 carbon atoms is a C 1 -C 6 alkyl. Alkyls (and other moieties defined herein) comprising other numbers of carbon atoms are represented similarly. Alkyl groups include, but are not limited to, C 1 -C 10 alkyl, C 1 -C 9 alkyl, C 1 -C 8 alkyl, C 1 -C 7 alkyl, C 1 -C 6 alkyl, C 1 -C 5 alkyl, C 1 -C 4 alkyl, C 1 -C 3 alkyl, C 1 -C 2 alkyl, C 2 -C 8 alkyl, C 3 -C 8 alkyl and C 4 -C 8 alkyl. Representative alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (i-propyl), n-butyl, i-butyl, s-butyl, n-pentyl, 1,1-dimethylethyl (t-butyl), 3-methylhexyl, 2-methylhexyl, 1-ethyl-propyl, and the like. The alkyl may be methyl or ethyl. The alkyl may be -CH(CH 3 ) 2 or -C(CH 3 ) 3 . Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted as described below.

[0180] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group. The alkylene may be -CH 2 -, -CH 2 CH 2 -, or - CH 2 CH 2 CH 2 -. The alkylene may be -CH 2 -. The alkylene may be -CH 2 CH 2 -. The alkylene may be - CH 2 CH 2 CH 2 -. The alkylene may be -CH 2 C(CH 3 )CH 2 -.

[0181] "Alkoxy" refers to a radical of the formula -OR where R is an alkyl radical as defined. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted as described below. Representative alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, pentoxy. The alkoxy may be methoxy. The alkoxy may be ethoxy.

[0182] "Alkenyl" refers to a type of alkyl group in which at least one carbon-carbon double bond is present. An alkenyl group may have the formula -C(R a< )=C(R a< ) 2 , wherein each R a< refers to the remaining portions of the alkenyl group, which may be the same or different. Each R a< may be hydrogen or an alkyl group. An alkenyl may be selected from ethenyl (i.e., vinyl), propenyl (i.e., allyl), butenyl, pentenyl, pentadienyl, and the like. Non-limiting examples of an alkenyl group include -CH=CH 2 , -C(CH 3 )=CH 2 , -CH=CHCH 3 , -C(CH 3 )=CHCH 3 , and -CH 2 CH=CH 2 .

[0183] "Heteroalkylene" refers to an alkyl radical as described above where one or more carbon atoms of the alkyl is replaced with a O, N or S atom. "Heteroalkylene" or "heteroalkylene chain" refers to a straight or branched divalent heteroalkyl chain linking the rest of the molecule to a radical group. Unless stated otherwise specifically in the specification, the heteroalkyl or heteroalkylene group may be optionally substituted as described below. Representative heteroalkyl groups include, but are not limited to -OCH 2 OMe, -OCH 2 CH 2 OMe, or -OCH 2 CH 2 OCH 2 CH 2 NH 2 . Representative heteroalkylene groups include, but are not limited to -OCH 2 CH 2 O-, -OCH 2 CH 2 OCH 2 CH 2 O-, or - OCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 O-.

[0184] "Alkylamino" refers to a radical of the formula -NHR or -NRR where each R is, independently, an alkyl radical as defined above. Unless stated otherwise specifically in the specification, an alkylamino group may be optionally substituted as described below.

[0185] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2 π electrons, where n is an integer. Aromatics can be optionally substituted. The term "aromatic" includes both aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups (e.g., pyridinyl, quinolinyl).

[0186] "Aryl" refers to an aromatic ring wherein each of the atoms forming the ring is a carbon atom. Aryl groups can be optionally substituted. Examples of aryl groups include, but are not limited to phenyl, and naphthyl. The aryl may be phenyl. Depending on the structure, an aryl group can be a monoradical or a diradical (i.e., an arylene group). Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals that are optionally substituted.

[0187] "Carboxy" refers to -CO 2 H. Carboxy moieties may be replaced with a "carboxylic acid bioisostere", which refers to a functional group or moiety that exhibits similar physical and / or chemical properties as a carboxylic acid moiety. A carboxylic acid bioisostere has similar biological properties to that of a carboxylic acid group. A compound with a carboxylic acid moiety can have the carboxylic acid moiety exchanged with a carboxylic acid bioisostere and have similar physical and / or biological properties when compared to the carboxylic acid-containing compound. For example, a carboxylic acid bioisostere would ionize at physiological pH to roughly the same extent as a carboxylic acid group. Examples of bioisosteres of a carboxylic acid include, but are not limited to: and the like.

[0188] "Cycloalkyl" refers to a monocyclic or polycyclic non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. Cycloalkyls may be saturated, or partially unsaturated. Cycloalkyls may be fused with an aromatic ring (in which case the cycloalkyl is bonded through a non-aromatic ring carbon atom). Cycloalkyl groups include groups having from 3 to 10 ring atoms. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to ten carbon atoms, from three to eight carbon atoms, from three to six carbon atoms, or from three to five carbon atoms. Monocyclic cycloalkyl radicals include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. The monocyclic cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The monocyclic cycloalkyl may be cyclopentyl. Polycyclic radicals include, for example, adamantyl, norbornyl, decalinyl, and 3,4-dihydronaphthalen-1(2H)-one. Unless otherwise stated specifically in the specification, a cycloalkyl group may be optionally substituted.

[0189] "Fluoroalkyl" refers to an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom. In one aspect, a fluoroalkyl is a C 1 -C 6 fluoroalkyl. A fluoroalkyl may be selected from trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like.

[0190] "Fused" refers to any ring structure described herein which is fused to an existing ring structure. When the fused ring is a heterocyclyl ring or a heteroaryl ring, any carbon atom on the existing ring structure which becomes part of the fused heterocyclyl ring or the fused heteroaryl ring may be replaced with a nitrogen atom.

[0191] "Halo" or "halogen" refers to bromo, chloro, fluoro or iodo.

[0192] "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. Unless stated otherwise specifically in the specification, a haloalkyl group may be optionally substituted.

[0193] "Haloalkoxy" refers to an alkoxy radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethoxy, difluoromethoxy, fluoromethoxy, trichloromethoxy, 2,2,2-trifluoroethoxy, 1,2-difluoroethoxy, 3-bromo-2-fluoropropoxy, 1,2-dibromoethoxy, and the like. Unless stated otherwise specifically in the specification, a haloalkoxy group may be optionally substituted.

[0194] "Heterocycloalkyl" or "heterocyclyl" or "heterocyclic ring" refers to a stable 3- to 14-membered non-aromatic ring radical comprising 2 to 10 carbon atoms and from one to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical may be a monocyclic, or bicyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom) or bridged ring systems. The nitrogen, carbon or sulfur atoms in the heterocyclyl radical may be optionally oxidized. The nitrogen atom may be optionally quaternized. The heterocycloalkyl radical is partially or fully saturated. 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, 1,1-dioxo-thiomorpholinyl. The term heterocycloalkyl also includes all ring forms of carbohydrates, including but not limited to monosaccharides, disaccharides and oligosaccharides. Unless otherwise noted, heterocycloalkyls have from 2 to 10 carbons in the ring. Heterocycloalkyls may have from 2 to 8 carbons in the ring. Heterocycloalkyls may have from 2 to 8 carbons in the ring and 1 or 2 N atoms. Heterocycloalkyls may have from 2 to 10 carbons, 0-2 N atoms, 0-2 O atoms, and 0-1 S atoms in the ring. Heterocycloalkyls may have from 2 to 10 carbons, 1-2 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e. skeletal atoms of the heterocycloalkyl ring). Unless stated otherwise specifically in the specification, a heterocycloalkyl group may be optionally substituted.

[0195] "Heteroaryl" refers to an aryl group that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur. The heteroaryl is monocyclic or bicyclic. Illustrative examples of monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, furazanyl, indolizine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. Illustrative examples of monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl. Illustrative examples of bicyclic heteroaryls include indolizine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. Heteroaryl may be pyridinyl, pyrazinyl, pyrimidinyl, thiazolyl, thienyl, thiadiazolyl or furyl. A heteroaryl may contain 0-4 N atoms in the ring. A heteroaryl may contain 1-4 N atoms in the ring. A heteroaryl may contain 0-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. A heteroaryl may contain 1-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. A heteroaryl may be a C1-C9heteroaryl. Monocyclic heteroaryl may be a C1-C5heteroaryl. Monocyclic heteroaryl may be a 5-membered or 6-membered heteroaryl. A bicyclic heteroaryl may be a C6-C9heteroaryl.

[0196] The term "optionally substituted" or "substituted" means that the referenced group may be substituted with one or more additional group(s) individually and independently selected from alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, aryl sulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, C 1 -C 6 alkylalkyne, halogen, acyl, acyloxy, -CO 2 H, -CO 2 alkyl, nitro, and amino, including mono- and di-substituted amino groups (e.g. -NH 2 , -NHR, -N(R) 2 ), and the protected derivatives thereof. Optional substituents may be independently selected from alkyl, alkoxy, haloalkyl, cycloalkyl, halogen, -CN, -NH 2 , -NH(CH 3 ), -N(CH 3 ) 2 , -OH, -CO 2 H, and -CO 2 alkyl. Optional substituents may be independently selected from fluoro, chloro, bromo, iodo, -CH 3 , -CH 2 CH 3 , -CF 3 , -OCH 3 , and -OCF 3 . Substituted groups may be substituted with one or two of the preceding groups. An optional substituent on an aliphatic carbon atom (acyclic or cyclic, saturated or unsaturated carbon atoms, excluding aromatic carbon atoms) may include oxo (=O). Compounds described herein can contain one or more double bonds and, thus, potentially give rise to cis / trans (E / Z) isomers, as well as other conformational isomers. Unless stated to the contrary, the compounds disclosed herein include all such possible isomers, as well as mixtures of such isomers.

[0197] PSB and PFPA-PSB are used interchangeably and refer to poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate).

[0198] Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers such as Aldrich Chemical Co., Milwaukee, Wis.), Acros Organics (Morris Plains, N.J.), Fisher Scientific (Pittsburgh, Pa.), or Sigma (St. Louis, Mo.) or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplemental volumes (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991); March's Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition); and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989).

[0199] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the appended claims or description that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification.EXAMPLES

[0200] The following examples are provided for illustrative purposes only, and are intended to be purely exemplary of the disclosure and are not intended to limit the scope of the appended claims. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for.Materials

[0201] α-Bromoisobutyryl bromide, N-Boc-ethanolamine, Trifluoroacetic acid, 1,1,4,7,10,10-Hexamethyltriethylenetetramine (97%), [2-(Methacryloyloxy) ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, tetrabutylammonium chloride, and cupper(I) chloride are used as received from Sigma Aldrich. Sodium bicarbonate, methylene chloride, magnesium sulfate, and 2,2,2-trifluoroethanol are purchased from Alfa Aesar. Sylgard 184 kit (Dow Corning) is obtained from Fisher Chemical.

[0202] The zwitterionic polymer, polysulfobetaine (PSB), is selected as an antifouling component of the coating. By adsorbing water electrostatically, PSB coatings form a thin hydration barrier that prevents organic material from adhering to its surface. Commonly used approaches to attach PSB coatings to surfaces such as radical-initiated graft polymerizations of PSB-methacrylate necessitate the use of oxygen-free conditions, preconditioning steps, or long reaction times that do not meet the scalability requirements. To circumvent the use of air-free graft polymerizations, we employ perfluorophenylazide (PFPA) as a molecular anchor to graft the PSB coating to the surface of polymeric materials under ambient conditions. When triggered with UV-light, PFPA moieties generate a highly reactive nitrene that forms covalent bonds with materials containing amines, C=C double bonds, and C-H bonds. With this method, it is surprisingly found that PSB is rapidly coated to a variety of substrates using UV light under ambient conditions with no preconditioning steps needed. In addition, it is unexpectedly found that water provides an optimal solvent for photografting of PFPA-PSB coating and that photografting of PFPA-PSB does not proceed well in the presence of organic solvents.Example 1. Synthesis of ATRP initiator 2-aminoethyl 2-bromoisobutyrate

[0203] ATRP initiator 2-aminoethyl 2-bromoisobutyrate is synthesized according to the following procedure. 5 g of 2-bromoisobutyryl bromide is added to a solution of 3.8 g of t-Boc-aminoethyl alcohol and 2.5 g of triethylamine in 12 ml methylene chloride in an ice bath. After 16 h, the salts are filtered off and the filtrate is extracted with saturated sodium bicarbonate solution. Methylene chloride phase is dried over magnesium sulfate and evaporated. The resulting t-Boc-aminoethyl 2-bromoisobutyrate is treated by 15 ml trifluoroacetic acid (TFA) for 2 h and crystallized upon addition of ethyl ether.Example 2. Synthesis of PFPAS-Methacrylate / acrylate

[0204]

[0205] 2-Aminoethyl methacrylate / acrylate hydrochloride is dissolved in DI Water at a concentration of 0.56M. 2 equivalents of sodium bicarbonate is added dropwise to the solution. In a separate vial, 1 equivalent of pentafluorobenzene sulfonyl chloride is dissolved in acetone at a concentration of 0.186M. Both solutions are cooled to 4°C. The solution containing 2-aminoethyl methacrylate / acrylate and sodium bicarbonate is added to the pentafluorobenzenesulfonyl chloride solution dropwise on ice. The reaction is stirred and gradually warmed up to room temperature. After 3 hours, 3 equivalents of sodium azide is added to the solution and the reaction is stirred for another 18 hours at room temperature. After, the acetone is removed under reduced pressure. Three times the reaction volume of methyl tert-butyl ether is added to the crude mixture and poured into a separatory funnel. DI water is added three times to wash the organic layer. The methyl tert-butyl ether is removed under reduced pressure to give the desired product.Example 3. Synthesis of PFPAA-Methacrylate / methacrylamide / acrylate / acrylamide

[0206]

[0207] 4-azidotetrafluorobenzoic acid was prepared according a published procedure by Keana et al. (J. Org. Chem. 1990, 55(11), 3640-7). To prepare the PFPAA-methacrylate: N-3-aminopropylmethacrylate hydrochloride and triethylamine are dissolved in dichloromethane to a concentration of 0.31M each. This solution is allowed to stir for 3 hours. The 4-azidotetrafluorobenzoic acid is then dissolved at a concentration of 0.235M. 4-dimethylaminopyridine is then added to the solution containing the 4-azidotetrafluorobenzoic acid (0.26M). A second portion of triethylamine is added so that the final concentration of triethylamine in the reaction is 0.56M. The reaction is then stirred for 48 hours, washed 3x with DI water, and the organic layer evaporated under reduced pressure to give the desired product. This procedure is used to prepare different PFPA amide - methacrylate / methacrylamide / acrylate / acrylamide compounds.Example 4. Synthesis of PFPAE-methacrylate / methacrylamide / acrylate / acrylamide

[0208]

[0209] 4-azidotetrafluorobenzoic acid was prepared according a published procedure by Keana et al. (J. Org. Chem. 1990, 55(11), 3640-7). To prepare the PFPAE-methacrylamide: 2-Hydroxyethyl methacrylamide and triethylamine are dissolved in dichloromethane to a concentration of 0.31M each. This solution is allowed to stir for 3 hours. The 4-azidotetrafluorobenzoic acid is then dissolved at a concentration of 0.235M. 4-Dimethylaminopyridine is then added to the solution containing the 4-azidotetrafluorobenzoic acid (0.26M). A second portion of triethylamine is added so that the final concentration of triethylamine in the reaction is 0.56M. The reaction is then stirred for 48 hours, washed 3X with DI water, and the organic layer evaporated under reduced pressure to give the desired product. This procedure is used to prepare different PFPA ester - methacrylate / methacrylamide / acrylate / acrylamide compounds.Example 5. Copolymer formation by polymerization of sulfobetaine methacrylate and perfluorophenylazide

[0210]

[0211] The copolymer is synthesized as follows: 2 g sulfobetaine methacrylate monomer 5-1, 100 mg, 150 mg, or 200 mg of perfluorophenylazide monomer 5-2, and 2 g tetrabutylammonium chloride are dissolved in 30 mL trifluoroethanol in a Schlenk flask and undergo two vacuum-argon cycles. Then, 14 mg Cu(I)Cl and 76 µL 1,1,4,7,10,10-hexamethyltriethylenetetramine are added. The Schlenk flask is sealed with a rubber septum and another two vacuum-argon cycles are performed. Finally, 44 mg TFA protected 2-aminoethyl 2-bromoisobutyrate as ATRP initiator is dissolved in a small amount of trifluoroethanol (~0.5 mL) and syringe-injected into the Schlenk flask, followed by two additional vacuum-argon cycles. Polymerization is carried out at 60 °C under argon. After 24 h, the reaction mixture is cooled down to room temperature and the copolymer is purified by performing membrane dialysis using a membrane with cut off molecular weight of 1000 Dalton. The resulting copolymer is freeze-dried before further use.

[0212] NMR spectra are recorded on a Bruker DPX300 spectrometer. Chemical shifts are calibrated to residual solvent signals. Molecular weights and dispersities are measured by gel permeation chromatography on a Shimadzu HPLC system with a refractive index detector S3 RID-10A, one Tosoh TSKGel guard column, and one Tosoh TSKGel G4000PW column. Eluent is 0.1 M NaNO 3 + 20 mM phosphate buffer pH 7 + 20% MeCN at 25 °C (flow rate 0.7 mL / min). Calibration is performed using near-monodisperse PEG standards from Polymer Laboratories. Light scattering is used to obtain the absolute molecular weight.Example 6. Synthesis of mixed charged copolymers

[0213]

[0214] Monomers 6-2, 6-3, and 6-4 are dissolved in different molar ratios in a solution of 4:1 TFE:DMF at a total concentration of 0.37M. 6-1 is added at a concentration of 0.022M and the radical initiator (AIBN) is added at a concentration of 0.0037M. The reaction is performed protected under argon gas using common Schlenk line technique. The oxygen is removed under reduced pressure and back-filled with argon gas three times. The reaction is stirred by mechanical stir bar and is heated to 60 °C using oil bath. After 72h, the reaction solvent is removed under reduced pressure with a rotary evaporator to 1 / 4 th< of the original reaction volume. Once concentrated, the polymer crude mixture is diluted with 10 times its volume with DI water. Residual monomers and oligomers are removed by pipetting the crude polymer reaction mixture into cellulose dialysis bags, with a 10,000 Dalton molecular weight cut-off, and placing the filled dialysis bag into a large water bath. The water bath is replenished with fresh deionized water continuously over 7 days. The purified polymer solution, now dispersed in water inside the dialysis bags, are freeze-dried to remove the water to yield a white powder. To synthesize mixed charged copolymers of different isoelectric points, the molar ratios of 6-2, 6-3, and 6-4 can be modified.Example 7. Synthesis of mixed charged copolymers

[0215]

[0216] Monomers 6-3 and 6-4 are dissolved in different molar ratios in a solution of 4:1 TFE:DMF at a total concentration of 0.37M. 6-1 is added at a concentration of 0.022M and the radical initiator (AIBN) is added at a concentration of 0.0037M. The reaction is performed protected under argon gas using common Schlenk line technique. The oxygen is removed under reduced pressure and back-filled with argon gas three times. The reaction is stirred by mechanical stir bar and is heated to 60 °C using oil bath. After 72h, the reaction solvent is removed under reduced pressure with a rotary evaporator to 1 / 4 th< of the original reaction volume. Once concentrated, the polymer crude mixture is diluted with 10 times its volume with DI water. Residual monomers and oligomers are removed by pipetting the crude polymer reaction mixture into cellulose dialysis bags, with a 10,000 Dalton molecular weight cut-off, and placing the filled dialysis bag into a large water bath. The water bath is replenished with fresh deionized water continuously over 7 days. The purified polymer solution, now dispersed in water inside the dialysis bags, are freeze-dried to remove the water to yield a white powder. To synthesize mixed charged copolymers of different isoelectric points, the molar ratios of 6-3 and 6-4 can be modified.Example 8. Synthesis of PFPA-positive and PFPA-negative charged copolymers

[0217] A surface containing a 1:1 molar ratio of positive and negative moieties is hypothesized to possess great antifouling properties. To achieve the 1:1 molar ratio of positive and negative moieties on the surface, two separate copolymers can be polymerized, each copolymer containing either positive charged moieties or negative charged moieties, and then blending them together in a 1:1 molar ratio in solution. An example of this is demonstrated below.

[0218] To synthesize a negatively charged PFPA-sulfonic acid copolymer, monomer 6-3 is dissolved in a solution of 4:1 TFE:DMF at a concentration of 0.37M. 6-1 is added at a concentration of 0.022M and the radical initiator (AIBN) is added at a concentration of 0.0037M. The reaction is performed protected under argon gas using common Schlenk line technique. The oxygen is removed under reduced pressure and back-filled with argon gas three times. The reaction is stirred by mechanical stir bar and is heated to 60 °C using oil bath. After 72h, the reaction solvent is removed under reduced pressure with a rotary evaporator to 1 / 4th of the original reaction volume. Once concentrated, the polymer crude mixture is diluted with 10 times its volume with deionized water. Residual monomers and oligomers are removed by pipetting the crude polymer reaction mixture into cellulose dialysis bags, with a 10,000 Dalton molecular weight cut-off, and placing the filled dialysis bag into a large water bath. The water bath is replenished with fresh deionized water continuously over 7 days. The purified polymer solution, now dispersed in water inside the dialysis bags, are freeze-dried to remove the water to yield a white powder.

[0219] To synthesize a positively charged PFP A-quaternary ammonium copolymer, monomer 6-4 is dissolved in a solution of 4:1 TFE:DMF at a concentration of 0.37M. 6-1 is added at a concentration of 0.022M and the radical initiator (AIBN) is added at a concentration of 0.0037M. The reaction is performed protected under argon gas using common Schlenk line technique. The oxygen is removed under reduced pressure and back-filled with argon gas three times. The reaction is stirred by mechanical stir bar and is heated to 60 °C using oil bath. After 72h, the reaction solvent is removed under reduced pressure with a rotary evaporator to 1 / 4th of the original reaction volume. Once concentrated, the polymer crude mixture is diluted with 10 times its volume with deionized water. Residual monomers and oligomers are removed by pipetting the crude polymer reaction mixture into cellulose dialysis bags, with a 10,000 Dalton molecular weight cut-off, and placing the filled dialysis bag into a large water bath. The water bath is replenished with fresh deionized water continuously over 7 days. The purified polymer solution, now dispersed in water inside the dialysis bags, are freeze-dried to remove the water to yield a white powder.

[0220] Once powders of each of the positively charged copolymer and negatively charged copolymer are obtained, they can be each added into a suitable solvent (H 2 O, DMF, 2,2,2-trifluoroethanole, DMSO, DMAc, etc) to make a 1:1 molar ratio of sulfonic acid moieties and quaternary ammonium moieties. The resulting mixture is used to modify a surface.Example 9. UV light silicone surface modification and characterization

[0221] Copolymer of Example 5 or 6 is dissolved or suspended in DI water to prepare 2-20 mg / mL aqueous mixture. Silicone elastomer films are prepared by mixing 10: 1 (by weight) base: crosslinker (Sylgard 184), followed by degassing under vacuum and subsequently crosslinking at 70 °C for 8 h. For anti-biofouling experiments, 2 mg / mL of copolymer aqueous mixture is spread onto a cured silicone elastomer surface and exposed to 254 nm UV light irradiation for 10 mins. Then the silicone elastomer surface is rinsed with large amounts of DI water to remove unreacted and physically adsorbed copolymer molecules from the surface and stored underneath a layer of water before further use.

[0222] Contact angles of deionized water (18 MΩ / cm, Millipore) on polymer coatings are measured using a rame-hart Model 590 goniometer. Advancing angles (θ adv ) are measured as water is supplied via a syringe, while receding angles (θ rec ) are measured as water is removed via a syringe. The total drop volume is about 5 µL, and the pump dispensing speed is about 0.2 µL / s. Measurements are taken over three or more different locations on each surface, and the reported values are in the format of average ± standard deviation.

[0223] For surface modification, the following photoreaction takes place. First, PFPA decomposes by releasing N 2 to give the singlet phenylnitrene upon activation of the compound by UV light. The singlet phenylnitrene further undergoes C-H or N-H insertion, and C=C addition reactions which contributes to the covalent bond formation with the target surfaces (Liu, L.-H. et al. Perfluorophenyl azides: new applications in surface functionalization and nanomaterial synthesis. Accounts of Chemical Research 2010, 43 (11), 1434-1443). In this process, "the singlet phenylnitrene" reaction intermediate is a strong nucleophile and its stability is not affected by the existence of oxygen and water molecules.Example 10. Silicone surface heat modification and characterization

[0224] Four 2cm segments of a catheter (16fr) were immersed in a 10mg / mL solution of PFPA-PSB copolymer dissolved in DI water in a sealed flask and subjected to a 1h heating period at various temperatures (80 °C, 100 °C, 120 °C, 140 °C, 160 °C, 180 °C, 200 °C, or 220 °C). The catheter segments were then removed from the solution and rinsed by slowly dipping twice in fresh DI water and blotted on a paper towel to remove any liquid from the interior lumens of the samples. The catheters were then allowed to dry

[0225] A dye solution of 3mg / mL Crystal Violet-HCl solution in DI water was stirred overnight. The modified catheter segments and an analogous set of unmodified catheter segments were immersed individually in the crystal violet solution for 1 minute and then rinsed by dipping twice in fresh DI water blotted on a paper towel to remove any liquid from the interior lumens of the samples. The catheter segments were then placed into scintillation vials.

[0226] 10mL of a 2:1 solution of DI Water: Acetic acid was then added to each vial. Each vial was shaken vigorously for 30 seconds to remove all adsorbed crystal violet from the catheters. 2mL of solution was removed from each tube, placed into a cuvette, and the absorbance at 580 nm was taken. Because the initial readings were too high, each solution was then diluted by a factor of 2. The absorbance measurement at 580 nm for the unmodified (control) and modified catheters by thermal treatment at different temperatures are listed in Table E-10 below. Table E-10. T, °CAbsorbances at 580 nmN / A0.104 (control)800.2961000.3471200.4921400.4581600.6151800.6852000.6522201.486 Example 11. Substrates modification and characterization

[0227] Coating substrates with PSB: PDMS substrates are prepared by mixing a 10:1 ratio of elastomer to curing agent, followed by curing at 80 °C for 1 h. The PDMS disks are cut with a laser cutter into 3 mm diameter disks. 30 µL of coating (PSB) mixture with concentrations ~ 2, 5, or 10 mg mL -1< is placed and spread out on the surface of each disk. The PSB is then crosslinked on the discs by exposing them to 254 nm UV light for 10 min under sterile conditions, followed by rinsing with Milli-Q water and drying with air.

[0228] Contact angle visualization and measurement: Water contact angle on various substrates, such as PDMS, Nylon 66, polystyrene, polyvinyl chloride, and polyethylene is visualized by placing 17 µL of Milli-Q water on the flat substrates at room temperature followed by imaging them. The images are analyzed using Fta32 version 2.1 software to measure the contact angle. To study the recovery of water contact angle on PDMS substrates, they are divided into two groups: (i) uncoated PDMS sheets, which are treated using O 2 plasma (Plasma Etch PE25-JW Plasma Cleaner, NV, US) for 1 min, followed by measuring water contact angle after 1, 2, 4, 7, and 10 days, and (ii) PDMS sheets that are coated with PSB, and the contact angle is similarly measured over time.

[0229] XPS studies are carried out on a Kratos AXIS Ultra DLD with a monochromatic Al Kα X-ray source operating at 10 mA and 15 kV. Survey spectra and individual high-resolution spectra are collected using pass energies of 160 and 20 eV, respectively. Data processing are performed using CasaXPS 2.3 software, and spectra binding energies are calibrated by assigning the hydrocarbon peak in the C1s high-resolution spectra to 284.6 eV

[0230] Cell culture: NIH / 3T3 fibroblast cells are cultured in cell culture flasks containing DMEM with 10% FBS and 1% P / S and passaged twice a week. For this purpose, a standard cell culture incubator (Thermo Fisher Scientific, PA, USA) is used to provide 5% CO 2 atmosphere and temperature = 37 °C. To conduct cell studies, 0.5% trypsin-EDTA is used to trypsinize fibroblast cells and count them using a hemocytometer, followed by seeding them on desirable substrates.

[0231] Cell adhesion: Trypsinized fibroblasts cells are seeded on PSB-coated 96-well plates by placing 100 µL of the cell suspension (cell density ~ 1 ×10 5< in 1 mL media) on the treated well plates, cultured for 24 h. Uncoated well plates are used as a control.

[0232] Cytotoxicity evaluation: To assess the cytotoxicity of un-crosslinked PSB, trypsinized fibroblasts cells are seeded on 96-well plates by placing 100 µL of the cell suspension (cell density ~ 1 ×10 5< in 1 mL media) and cultured for 24 h, followed by adding a desired amount of un-crosslinked PSB to the media and further culturing for 72 h. The cytotoxicity of crosslinked PSB is evaluated by seeding 500 µL of cell suspension (cell density ~ 2 ×10 5< in 1 mL media) in 24-well plates, culturing for 24 h, followed by placing PSB coated PDMS discs (diameter ~ 6 mm, height ~ 3 mm) in the medium and further culturing for 72 h.

[0233] Metabolic activity assessment: MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (Thermo Fisher Scientific) stain solutions are prepared at a concentration ~ 5 mg mL -1< in DPBS. Cell culture media are removed from the well plates, followed by one time rinsing with DPBS. The wells are then loaded with fresh media and MTT solution at a ratio of 9:1. The well plates are wrapped with aluminum foil and incubated for 4 h at 37°C and 5% CO 2 . After 4 h, the wells are aspirated with a pipette and 200 or 500 µL of DMSO is added for 96- and 24-well plates, respectively. The well plates are wrapped with aluminum foil again and left on a rotator for 30 min, after which absorbance is recorded at 570 nm using a microplate reader (Synergy HTX multi-mode reader, BioTek, VT, USA).

[0234] Live / Dead assay: To assess the cell viability, a live / dead fluorescence assay is used. The staining solution is prepared by adding ethidium homodimer-1 (20 µL) and calcein AM (5 µL) to DPBS (10 mL). To perform the assay, the cells are incubated with 1 mL of the staining solution for approximately 20 min and imaged using a fluorescent microscope (Axio Observer 5, Zeiss, Germany) at excitation / emission wavelengths ~ 494 / 515 nm for calcein and 528 / 617 nm for ethidium homodimer-1.

[0235] Protein adsorption: The protein adsorption is assessed by incubating 100 µg of 50 µg mL -1< of Alexa Fluor ™< 488 (AF)-conjugated BSA on each PDMS substrate for 1 h at 37 °C. To inhibit the photodegradation of AF, aluminum foil is used to wrap the substrates. Then, the PDMS substrates are gently rinsed with Milli-Q water and imaged at a constant exposure time ~ 1.13 ms using a fluorescent microscope (Axio Observer 5, Zeiss, Germany) at excitation / emission wavelengths ~ 488 / 517 nm. ImageJ (National Institutes of Health, US) is used to quantify the emitted fluorescence via the mean gray value analysis tool. The average pixel brightness indirectly reflects the amount of protein adsorbed to the substrates. Background autofluorescence is eliminated using AF-free samples as control.

[0236] Bacterial culture: Bacterial species, E. coli, S. epidermidis, S. aureus Rosenbach, S. aureus (MRSA), P. aeruginosa, and C. albicans are used in this work. All strains are incubated at 30°C at 150 rpm until a mid-exponential phase is reached, at which time the cells are harvested by centrifugation at 3800 xg for 8 min. E. coli is grown on a Luria-Bertani (LB) broth, S. epidermidis, P. aeruginosa, and S. aureus Rosenbach are grown on nutrient broth; S. aureus (MRSA) is grown on a trypticase soy broth (TSB); and C. albicans is grown on a yeast mold (YM) broth. These initial cultures are then adjusted to an optical density of 1 at 600 nm and had an initial total cell number ranging from 1×10 7< cells per mL to 1×10 8< cells per mL.

[0237] Bacterial adhesion: 55 mm diameter Petri dishes are filled with a 10:1 elastomer to curing agent (Sylgard 184) and allowed to cure at room temperature for at least 48 hours to form a 3mm thick PDMS film on the bottom of the dishes. Modified plates are coated with a solution containing PFPA-PSB and irradiated with 254 nm UV light. Each modified and unmodified PDMS-lined dish is inoculated with 4 mL of bacterial or fungal suspension and incubated for 24-72 hours (shaken at 25 rpm) at 35 °C. The bacterial or fungal suspension is then removed and stored for further microscopy. The Petri dishes are gently rinsed with sterile, deionized water using a Pasteur pipette, and covered in 4 mL of a dye solution (SYTO 9 live / dead Baclight Bacterial Viability Kit L13152, Molecular Probes) for 15 min. The SYTO 9 solution is prepared by dissolving the contents of component A of the kit in 30 mL of sterile, deionized water. After the staining is complete, the Petri dishes are gently rinsed with deionized water and imaged using a 4x CCD camera (Axiocam MRm System) attached to a Zeiss Axioskop 2 microscope with a 10x objective, 40x objective, a fluorescent lamp, and a blue excitation filter. During observation, the images are taken at an excitation range of 450-490 nm. The number of attached microorganisms on all fluorescent images are determined using ImageJ software.

[0238] Statistical analysis: The data are reported as mean values ± standard deviation of at least triplicate experiments. The one-way analysis of variance (ANOVA) and Tukey's multiple comparisons are used, and statistically significant differences are identified for p-values lower than 0.05 (*p<0.05), 0.01 (**p<0.01), 0.001 (***p<0.001), and 0.0001 (****p<0.0001).

[0239] Escherichia coli is used as the model bacteria for this test. Pure bacterial cell cultures are suspended in Luria-Bertani (LB) broth and grown at 35 °C while being shaken at 150 rpm and incubated until a mid-exponential phase is reached, at which time the cells are harvested by centrifugation at 3800×g for 8 min. The cells are then re-suspended with fresh LB medium to a concentration of 4×10 7< cells / mL. Membrane coupons, of approximately 1 cm 2< , are incubated in this bacterial suspension for 24 hr at 25 rpm and 35°C. The coupons are then removed from the suspension and gently rinsed with fresh LB broth using a Pasteur pipette. Once rinsed, the coupons are immersed in a dye solution (SYTO 9 live / dead Baclight Bacterial Viability Kit L13152, Molecular Probes) for 15 min. The SYTO 9 solution is prepared by dissolving the contents of component A of the kit in 30 mL of sterile distillated water. After the staining is complete, the coupons are gently rinsed with fresh LB broth and imaged using a microscope (Olympus BX51 microscope) equipped with a fluorescent lamp and green / red fluorescence filters and a 4x CCD camera attachment (FVIEW-II, Soft Imaging System, USA).

Claims

1. A copolymer comprising: a) a repeating unit of Formula (VII): wherein each R1a and R1b is independently selected from hydrogen and halogen; each R2a and R2b is independently selected from halogen, -CN, and optionally substituted C1-C6 fluoroalkyl; each A1 and A2 is independently selected from -C(=O)-, -S(=O)-, -S(=O)2-, and-S(=O)(=NR3c)-; each B1 and B2 is independently selected from -O- and -NR3c-; Z1 is -(CR6cR6d),-; each R4c, R4d, R5d, R5e, R6c, and R6d is independently selected from hydrogen, halogen, -CN, -OR9a, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 fluoroalkyl, optionally substituted C2-C6 alkenyl, -NR3cR3d, -S(=O)2O-, -S(=O)2OR9a, -C(=O)O-, and -C(=O)OR9a; each R3c and R3d is independently selected from hydrogen, optionally substituted C1-C4 alkyl, -X-optionally substituted C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O)2-; each R9a, R11a, R11b, and R11c is independently selected from hydrogen, optionally substituted C1-C4 alkyl, and optionally substituted aryl; n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; and s is an integer selected from 1, 2, 3, 4, and 5; b) a repeating unit of Formula (VIII): wherein, A3 is -C(=O)-, -S(=O)-, -S(=O)2-, or -S(=O)(=NR3c)-; B3 is -O- or -NR3c-; D is -S(=O)2O-, -S(=O)2OR9a, -C(=O)O-, or -C(=O)OR9a; Z2 is -(CR6cR6d)t-; Z3 is -(CR6cR6d)p-; each R3a and R3b is independently selected from hydrogen, optionally substituted C1-C4 alkyl, and optionally substituted benzyl; each R6c and R6d is independently selected from hydrogen, halogen, -CN, -OR9a, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 fluoroalkyl, optionally substituted C2-C6 alkenyl, -NR3cR3d, -S(=O)2O-, -S(=O)2OR9a, -C(=O)O-, and -C(=O)OR9a; each R3c and R3d is independently selected from hydrogen, optionally substituted C1-C4 alkyl, -X-optionally substituted C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O)2-; each R9a, R12a, R12b, and R12c is independently selected from hydrogen, optionally substituted C1-C4 alkyl, and optionally substituted aryl; t is an integer selected from 1, 2, 3, 4, or 5; p is an integer selected from 1, 2, 3, 4, or 5; and wherein the repeating unit of Formula (VIII) is charged or zwitterionic; and c) a repeating unit of Formula (IX): A4 is -C(=O)-, -S(=O)-, -S(=O)2-, or -S(=O)(=NR3c)-; B4 is -O- or -NR3c-; Z4 is -(CR6cR6d)k-; E is -CN, -OR9a, -NR9aR9b, -NR9aR9bR9c+, optionally substituted C1-C4 alkyl, optionally substituted C1-C6 fluoroalkyl, -S(=O)2O-, -S(=O)2OR9a, -C(=O)O-, or -C(=O)OR9a; each R6c, and R6d is independently selected from hydrogen, halogen, -CN, -OR9a, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 fluoroalkyl, optionally substituted C2-C6 alkenyl, -NR3cR3d, -S(=O)2O-, -S(=O)2OR9a, -C(=O)O-, and -C(=O)OR9a; each R3c and R3d is independently selected from hydrogen, optionally substituted C1-C4 alkyl, -X-optionally substituted C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted aryl; X is -C(=O)-, -S(=O)-, or -S(=O)2-; each R9a, R9b, R9c, R13a, R13b, and R13c is independently selected from hydrogen, optionally substituted C1-C4 alkyl, and optionally substituted aryl; and k is an integer selected from 1, 2, 3, 4, or 5.

2. The copolymer of claim 1, wherein each R1a, R1b, R2a, and R2b is F.

3. The copolymer of claim 1 or 2, wherein A1 is -S(=O)2- and each A2, A3, and A4 is -C(=O)-.

4. The copolymer of any one of claims 1-3, wherein each B1, B2, and B3 is independently -O-or -NR3c-.

5. The copolymer of any one of claims 1-4, wherein each R3c is hydrogen or -CH3.

6. The copolymer of any one of claims 1-5, wherein D is -S(=O)2O- or -C(=O)O-.

7. The copolymer of any one of claims 1-6, wherein E is -NR9aR9bR9c+ or -S(=O)2OR9a.

8. The copolymer of any one of claims 1-7, wherein each R9a, R9b, and R9c is independently hydrogen or C1-C4 alkyl.

9. The copolymer of any one of claims 1-8, wherein each R3a and R3b is -CH3.

10. The copolymer of any one of claims 1-9, wherein each R3c, R3d, R4c, R4d, R5d, R5e, R6c, and R6d is hydrogen.

11. The copolymer of any one of claims 1-10, wherein each R11a, R12a, and R13a is hydrogen or-CH3, and each R11b, R11c, R12b, R12c, R13b, and R13c is hydrogen.

12. The copolymer of any one of claims 1-11, wherein n is 0, 1, or 2, and each s, t, p, and k is independently 1, 2 or 3.

13. A biofouling-resistant medical device, wherein a surface of the medical device is coated with a copolymer of any one of claims 1-12.

14. The biofouling-resistant medical device of claim 13, wherein the medical device comprises an implant, an IV, a prosthesis, suturing material, valve, stent, catheter, rod, shunt, scope, a contact lens, tubing, wiring, electrode, clip, fastener, syringe, container, or a combination thereof.

15. A method of making a biofouling-resistant medical device, comprising: a) contacting a surface of a device with a mixture comprising a copolymer of any one of claims 1-12; and b) treating the surface of the device of step a) with a heat source for a time sufficient to undergo thermografting of the copolymer onto the surface of the device, thereby making the biofouling-resistant device.