BACKGROUND OF THE INVENTION

Polymeric materials with excellent non-fouling properties are known. Polymeric materials with strong mechanical properties are also known. However, polymeric materials having both excellent non-fouling properties and strong mechanical properties are not known. Polymeric materials having excellent non-fouling properties generally have weak mechanical properties, and high-strength polymeric materials generally suffer from high protein adsorption.

Despite the development of polymeric materials having excellent non-fouling properties and the development of polymeric materials high-strength mechanical properties, a need exists for polymeric materials having both excellent non-fouling properties and high mechanical strength. The present invention seeks to fulfill this need and provides further related advantages.

SUMMARY OF THE INVENTION

The present invention provides polymeric materials having both excellent non-fouling properties and high mechanical strength. The polymeric materials are polymers and bulk materials prepared from monomers and macromonomers that impart advantageous non-fouling and high strength properties to the polymer and bulk materials.

In one aspect, the invention provides monomers useful for making polymers and bulk materials of the invention.

In one embodiment, the invention provides a monomer having a formula selected from the group consisting of:


and

wherein

R1is selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20alkyl, and C6-C12aryl groups, or CN;

R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, C1-C20alkyl, and C6-C12aryl, cyclic alkyl, fluoroalkyl, and void;

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening;

L is C or Si or void;

L1, L3, and L4are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and (CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

L2is independently selected from —(CH2)x—, or —(CH(CN))x—, where x is an integer from 1 to 20;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

C1is PO4; and

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, and salicylate, or void.

In another embodiment, the invention provides a monomer having a formula selected from the group consisting of:



wherein

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening;

L is C or Si or void;

L1, L2, L3, and L4are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

C1is PO4; and

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, and salicylate, or void.

In a further embodiment, the invention provides a monomer having a formula selected from the group consisting of:



wherein

R1and R6is selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20 alkyl, C6-C12 aryl, CN, cyclic alkyl, fluoro alkyl, and void;

R4, R5, R7, and R8are independently selected from the group consisting of hydrogen, C1-C20 alkyl, C6-C12 aryl, cyclic alkyl group, fluoro alkyl, and void;

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening;

L0and L4are C or Si or void;

L1, L2, L3, L5, and L6are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

C1is PO4; and

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20 alkyl), lactate, benzoate, salicylate, or void.

For each of the above embodiments, R2and R3may further be selected from a functional group suitable for free radical polymerization. Such functional groups are known to those in the art and include, for example, ethylenic moieties, such as vinyl moieties including vinyl esters and vinyl amides, among others.

In certain embodiments, the invention provides macromonomers useful for making the polymers and bulk materials of the invention.

In one embodiment, the invention provides a macromonomer having a formula selected from the group consisting of:



wherein

R1is selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20alkyl, C6-C12aryl, CN;

R4, R5, R6, and R7, are independently selected from the group consisting of hydrogen, C1-C20alkyl, C6-C12aryl, cyclic alkyl, fluoro alkyl, and void;

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization; L is C or Si or void;

L1, L3, and L4are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

L2is independently selected from —(CH2)x—, or —(CH(CN))x—, where x is an integer from 1 to 20;

A1is N;

B1is C, S, SO, PO, or PO2;

B2is C or SO;

C1is PO4;

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, salicylate, or void; and

j is an integer from 1 to about 1000.

In another embodiment, the invention provides a macromonomer having a formula selected from the group consisting of:



wherein

R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, C1-C20alkyl, C6-C12aryl, cyclic alkyl, fluoro alkyl, and void;

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization;

L is C or Si or void;

L1, L3, and L4are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and (CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

L2is independently selected from —(CH2)x—, or —(CH(CN))x—, where x is an integer from 1 to 20;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, salicylate, or void; and

j is an integer from 1 to about 1000.

In a further embodiment, the invention provides a macromonomer having a formula selected from the group consisting of:



wherein

R1and R6are selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20 alkyl, C6-C12 aryl, CN, cyclic alkyl, fluoroalkyl, and void;

R4, R5, R7, and R8are independently selected from the group consisting of hydrogen, C1-C20 alkyl, C6-C12 aryl, cyclic alkyl, fluoroalkyl, and void;

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization;

L0and L4are C or Si or void;

L1, L2, L3, L5, and L6are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

C1is PO4;

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20 alkyl), lactate, benzoate, and salicylate or void;

j and k are integers independently selected from 1 to about 1000.

In other embodiments, the invention provides monomers useful for making the polymers and bulk materials of the invention.

In one embodiment, the invention provides a monomer having the formula:



or a salt thereof,

wherein

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization;

Xais selected from —(CH2)n—, where n is 0 to 6;

Xbis —(CH2)p—, where p is 1 to 6;

Rais selected from hydrogen and C1-C6 alkyl;

Xcis —(CH2)q—, where q is 1 to 6; and

Y is selected from CO2−, SO3−, or PO42−.

In another embodiment, the invention provides a monomer having the formula:



or a salt thereof,

wherein

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization;

Xais selected from —(CH2)n—, where n is 0 to 6;

Xbis —(CH2)p—, where p is 1 to 6;

Ra, Rb, and Rcare independently selected from hydrogen and C1-C6 alkyl;

Xcis —(CH2)q—, where q is 1 to 6;

Xdis —(CH2)r—, where r is 1 to 6; and

Y is selected from CO2−, SO3−, or PO42−.

In a further embodiment, the invention provides a monomer having the formula:



or a salt thereof,

wherein

R2and R3are independently selected from a functional group suitable for polymerization by addition, condensation, or ring opening, or free radical polymerization;

Xais selected from —(CH2)n—, where n is 0 to 6;

Xbis —(CH2)p—, where p is 1 to 6;

Raand Rbare independently selected from hydrogen and C1-C6 alkyl; and

Xcis —(CH2)q—, where q is 1 to 6.

In certain embodiment of the monomers and macromonomers of the invention, R2and R3are independently selected from the group consisting of F, Cl, Br, I, SH, protected thiols, NH2, —NH— (secondary amine), N═C═O, protected NCO, N═C═S, COOH, COSH, C(═S)SH, OCOOH, OCOSH, OC(═S)OH, SC(═O)SH, SC(═S)SH, N(C═O)NH2, N(C═NH)NH2, N(C═S)NH2, δ-valerolactone moiety, ε-caprolactone moiety, CH2═CH—C(═O)—O—, CH2═CH—C(═O)—NH—, CH2═CH—C(═O)—S—, CN, CH2═CH(CH3)—C(═O)—O—, CH2═CH(CH3)—C(═O)—O—, OH, azides, alkynes, or void.

In certain embodiments, R2and R3are selected from the group consisting of —N═C═O and —N═C═S. In other embodiments, R2and R3are Michael acceptors, such as CH2═CH—C(═O)—O—, CH2═CH—C(═O)—NH—, CH2═CH—C(═O)—S—, CH2═CH(CH3)—C(═O)—O—, and CH2═CH(CH3)—C(═O)—O—. In further embodiments, R2and R3are ring opening polymerization moieties or ring opening metathesis polymerization moieties, such as



wherein

m and n are independently selected from 1 to 3.

R4and R5are independently selected from the group consisting of hydrogen, C1-C20alkyl, and C6-C12aryl, cyclic alkyl, fluoroalkyl, and void;

L1is independently selected from —(CH2)x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

L2is —(CH2)xwhere x is an integer from 1 to 20;

A1is N;

B2is C or SO; and

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, and salicylate, or void.

In certain embodiments, the monomer is a stabilizing monomer that imparts advantageous strength properties to the polymers and bulk materials of the invention.

In certain of these embodiments, the monomer is a CN-substituted monomer that imparts a CN group to the polymer backbone. In this embodiment, the monomer has the formula:



or a salt thereof,

wherein

Xais selected from —O(C═O)(CH2)n— where n is 1 to 6, —O(CH2)m— where m is 1 to 6, or is absent;

Raand Rbare independently selected from hydrogen and C1-C6 alkyl; and

Xbis —(CH2)n— where n is 1 to 6.

In certain of these embodiments, the monomer is a CN-substituted monomer that imparts a CN group to the polymer side chains. In this embodiment, the monomer has the formula:



or a salt thereof,

wherein

Xais selected from —O(C═O)(CH2)n—, where n is 1 to 6, or —NH(C═O)(CH2)m—, where m is 1 to 6;

Raand Rbare independently selected from hydrogen and C1-C6 alkyl; and

Xbis —(CH2)p—, where p is 1 to 6; and

Xcis —(CH2)q—, where q is 1 to 6.

In certain embodiments, the monomer is a stabilizing monomer that imparts advantageous strength properties to the polymers and bulk materials of the invention.

In certain of these embodiments, the stabilizing monomer is an amide- or diamide-containing monomer that imparts an amide or a diamide group to the polymer side chain. In one embodiment, the diamide-containing monomer has the formula:



or a salt thereof,

wherein

Xais selected from —(CH2)n—, where n is 0 to 6;

Xbis —(CH2)p—, where p is 1 to 6;

Raand Rbare independently selected from hydrogen and C1-C6 alkyl; and

Xcis —(CH2)q—, where q is 1 to 6.

In certain of these embodiments, the stabilizing monomer is a urea-containing monomer that imparts a urea group to the polymer side chain. In one embodiment, the urea-containing monomer has the formula:



or a salt thereof,

wherein

Xais selected from —(CH2)n—, where n is 0 to 6;

Xbis —(CH2)p—, where p is 1 to 6;

Raand Rbare independently selected from hydrogen and C1-C6 alkyl; and

Xcis —(CH2)q—, where q is 1 to 6.

In another aspect of the invention, polymers and bulk materials comprising the polymers are provided.

In certain embodiments, the polymer or bulk material is prepared by polymerizing a monomer or macromonomer of the invention, as described herein.

In other embodiments, the polymer or bulk material is prepared by polymerizing a monomer or macromonomer of the invention, as described herein, with a second monomer (e.g., a monomer that does not include either a zwitterionic or zwitterionic precursor group).

In certain embodiments, the polymer has the formula:
R2M1K1—Z—K2jM2-M1K3—X—K4jM2nR3

wherein

K1, K2, K3, and K4are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

R2and R3are independently selected from H, F, Cl, Br, I, OH, SH, protected thiols, NH2, —NH— (secondary amine), N═C═O, N═C═S, COOH, COSH, C(═S)SH, OCOOH, OCOSH, OC(═S)OH, SC(═O)SH, SC(═S)SH, N(C═O)NH2, N(C═NH)NH2, N(C═S)NH2, δ-valerolactone moiety, ε-caprolactone moiety, CH2═CH—C(═O)—O—, CH2═CH—C(═O)—NH—, CH2═CH—C(═O)—S—, CN, CH2═CH(CH3)—C(═O)—O—, CH2═CH(CH3)—C(═O)—NH—, or void;

n is an integer from 5 to about 10,000;

j is an integer from 1 to about 1000;

M1and M2are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void; and

Z and X are independently selected from zwitterionic groups.

In certain embodiments of these embodiments, Z and X are independently selected from the group consisting of



wherein

R1and R8are selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20 alkyl, and C6-C12 aryl groups, CN;

R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, C1-C20 alkyl, C6-C12 aryl, cyclic alkyl, fluoroalkyl, or void;

L is C or Si or void;

L1, L3, L4, and L5are independently selected from —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

L2is independently selected from —(CH2)x—, or —(CH(CN))x—, where x is an integer from 1 to 20;

A1is N;

B1is C, S, SO, PO, or PO2—;

B2is C or SO;

C1is PO4; and

M is selected from Cl, Br, I, SO4, NO3, ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20 alkyl), lactate, benzoate, salicylate, or void.

In certain embodiments, the polymer has a formula selected from the group consisting of:



wherein

R1and R5is selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C20alkyl, and C6-C12aryl groups, CN;

R2, R3, R4, and R6are independently selected from the group consisting of hydrogen, C1-C20alkyl, C6-C12aryl, cyclic alkyl, fluoroalkyl, or void;

L0and L5are independently C or Si or void;

L1, L2, L3, L4, L6, and L7are independently selected from —(CH2)x—, —(CH(CN))x—C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

M1and M2are independently selected from the group consisting of —O—(CH2)n—, —S—(CH2)n—, —C(═O)—(CH2)n—, —C(═S)—(CH2)n—, —C(═NH)—(CH2)n— and —NH—(CH2)n—, wherein n is an integer from 1 to 20; —(CH2)x—, —(CH(CN))x—, —C(═O)NH(CH2)x—, —C(═O)O(CH2)x—, —C(═O)OC(═O)O(CH2)x—, —(CH2)x—O—(CH2)x—, and —(CH2)x—S—S—(CH2)x—, where x at each occurrence is an integer independently selected from 0 to 20, combinations thereof, or void;

B1is C, S, SO, P, or PO;

B2is C or SO;

A1is N, S, or P;

M is selected from Cl, Br, I, SO4, NO3ClO4, BF4, PF6, N(SO2CF3)2, SO3CF3, RCOO (R is C1-C20alkyl), lactate, benzoate, salicylate, or void;

wherein the ratio between m and n is selected from 0.8 to 1.2; and

wherein m and n are independently integers from 1 to about 10,000.

In certain embodiments, the polymers and bulk materials of the invention have a fibrinogen binding level of less than 30 ng/cm2in a fibrinogen binding assay (polymer surface is incubated at 37° C. for 90 minutes with a 1.0 mg/mL fibrinogen solution in 0.15 M phosphate buffered saline at pH 7.4).

In certain embodiments, the polymers and bulk materials of the invention have a tensile or compressive strength greater than 0.5 MPa.

In certain embodiments, the polymers and bulk materials of the invention have a fibrinogen binding level of less than 30 ng/cm2in a fibrinogen binding assay (polymer surface is incubated at 37° C. for 90 minutes with a 1.0 mg/mL fibrinogen solution in 0.15 M phosphate buffered saline at pH 7.4) and a tensile or compressive strengths greater than 0.5 MPa.

In certain embodiments, the polymers and bulk materials of the invention are crosslinked.

In a further aspect, the invention provides composite that include the polymers and bulk materials of the invention.

In one embodiment, the composite comprises a polymer of the invention and a second polymer. Suitable second polymers include polyesters, polycarbonates, polyurethanes, polyureas, polysulfides, polysulfones, polyimides, polyepoxies, aromatic polyesters, cellulosics, fluoropolymers, polyacrylics, polyamides, polyanhydrides, polyethers, vinyl polymers, phenolics, elastomers, and other addition polymers.

In certain embodiments, the composite further includes a strength additive. Representative strength additives include fibers, clays, nanotubes, and other inorganic objects.

In certain embodiments, the polymers or bulk materials of the invention are formed into an object by a method selected from the group consisting of injection molding, blow molding, extrusion molding, calendaring molding, flow casting, compression molding, prevarication molding, and 3D printing.

In another aspect, the invention provides a surface coating for a substrate that includes a polymer or bulk material of the invention. In certain embodiments, the substrate is a consumer product. In other embodiments, the substrate is a marine product.

Representative marine products include marine vessel hulls, marine structures, bridges, propellers, heat exchangers, periscopes, sensors, fish nets, cables, tubes/pipes, containers, membranes, and oil booms. In further embodiments, the substrate is a biomedical product. Representative biomedical products include catheters, ear drainage tubes, feeding tubes, glaucoma drainage tubes, hydrocephalous shunts, keratoprosthesis, nerve guidance tubes, tissue adhesives, x-ray guides, artificial joints, artificial heart valves, artificial blood vessels, pacemakers, left ventricular assist devices (LVAD), artery grafts, vascular grafts, stents, intravascular stents, cardiac valves, joint replacements, blood vessel prostheses, skin repair devices, cochlear replacements, contact lenses, artificial ligaments and tendons, dental implants, and tissue scaffolds for regenerative tissue engineering. In certain other embodiments, the substrate is a delivery vehicle selected from the group consisting of a drug delivery vehicle, a gene delivery vehicle, an RNA delivery vehicle, a protein delivery vehicle.

In a further aspect, the invention provides conjugate polymers and bulk materials where the polymer or bulk material is coupled (e.g., covalently) to a biomolecule. Representative biomolecules include therapeutic agents, nucleic acids (e.g., gene or DNA or RNA), proteins (e.g., antibody or functional fragment thereof), lipids, peptides, or small molecules having a molecular weight less than about 800.

In certain embodiments, the polymer or bulk material is coupled (e.g., covalently) to a cell or microorganism.

In other embodiments, the polymer or bulk material is coupled (e.g., covalently) to a nanoparticle. Representative nanoparticles include liposomes and micelles, quantum dots, and iron oxide, silica, or gold nanoparticles.

