Antimicrobial copolymers and uses thereof

1 . A random copolymer of Formula III:

A-(B) n1 -(D) m1 -H  III

or an acceptable salt or solvate thereof, wherein:

A is the residue of a chain transfer agent;

B is —[CH 2 —C(R 11 )(B 11 )]—, wherein B 11 is —X 11 -Y 11 -Z 11 , and

X 11 is carbonyl (—C(═O)—) or optionally substituted C 1-6 alkylene; or X 11 is absent;

Y 11 is O, NH, or optionally substituted C 1-6 alkylene; or Y 11 is absent;

Z 11 is -Z 11A -Z 11B , wherein:

Z 11A is alkylene, arylene, or heteroarylene, any of which is optionally substituted; or Z 11A is absent;

Z 11B is -guanidino, -amidino, —N(R 3 )(R 4 ) or —N + (R 3 )(R 4 )(R 5 ), wherein R 3 , R 4 , and R 5 are independently hydrogen, alkyl, aminoalkyl, aryl, heteroaryl, heterocyclic, or aralkyl; or

Z 11 is pyridinium

 or phosphonium

wherein R 81 , R 911 , R 921 , and R 931 are independently hydrogen or alkyl;

D is —[CH 2 —C(R 21 )(D 21 )]—, wherein D 21 is -X 21 -Y 21 -Z 21 , and

X 21 is carbonyl (—C(═O)—) or optionally substituted C 1-6 alkylene; or X 21 is absent;

Y 21 is O, NH, or optionally substituted C 1-6 alkylene, or Y 21 is absent;

Z 21 is alkyl, cycloalkyl, alkoxy, aryl, or aralkyl, any of which is optionally substituted;

R 11 and R 21 are independently hydrogen or C 1-4 alkyl;

m 1 , the mole fraction of D monomer, is about 0.1 to about 0.9; and

n 1 , the mole fraction of B monomer, is 1−m 1 ;

wherein the copolymer is a random copolymer of B and D monomers, and

wherein the copolymer has a degree of polymerization of about 5 to about 50.

2 . The random copolymer of claim 1 , wherein A is C 1-4 alkoxycarbonyl(C 1-4 )alkylthio.

3 . The random copolymer of claim 2 , wherein:

X 11 and X 21 are carbonyl;

Y 11 and Y 21 are 0;

Z 11 is -Z 11A -Z 11B , wherein Z 11A is C 1-6 alkylene optionally substituted with C 1-4 alkyl or aryl; and Z 11B is —N(R 31 )(R 41 ) or —N + (R 31 )(R 41 )(R 51 ), wherein R 31 , R 41 , and R 51 are independently hydrogen, C 1-4 alkyl, amino(C 1-4 ) alkyl, C 1-6 aryl, or Cl 6 ar(C 1-4 )alkyl;

Z 21 is C 1-6 alkyl, C 1-6 aryl, or C 1-6 ar(C 1-4 )alkyl; and

R 11 and R 21 are independently hydrogen or methyl;

wherein the copolymer has a degree of polymerization of about 5 to about 25.

4 . The random copolymer of claim 3 , wherein Z 11A is C 1-4 alkylene optionally substituted with methyl or ethyl; and R 31 , R 41 , and R 51 are independently hydrogen or methyl.

5 . The random copolymer of claim 2 , wherein Z, 1 is pyridinium

 or phosphonium

wherein R 81 , R 911 , R 921 , and R 931 are independently hydrogen or C 1-4 alkyl.

6 . The random copolymer of claim 2 , wherein:

X 21 is carbonyl or optionally substituted C 1-4 alkylene;

Y 21 is O or NH; and

Z 21 is C 1-6 alkyl, C 1-6 aryl, or C 1-6 ar(C 1-4 )alkyl.

7 . The copolymer of claim 6 , wherein Z 21 is methyl, ethyl, n-butyl, isobutyl, hexyl, or benzyl.

8 . The random copolymer of claim 1 , wherein m 1 is about 0.35 to about 0.60.

9 . The random copolymer of claim 1 , wherein the degree of polymerization (DP) is about 5 to about 10.

10 . The random copolymer of claim 1 , wherein the random copolymer is of Formula IIIa:

or an acceptable salt or solvate thereof, wherein:

R 1a and R 2a are independently hydrogen or methyl;

R 3a , R 4a , and R 5a are independently hydrogen or C 1-4 alkyl;

R 6a is C 1-4 alkyl;

R 7a is C 1-10 alkyl, C 1-6 aryl, or C 1-6 ar(C 1-4 )alkyl;

p 1a is 1 to 4;

p 2a is 1 to 6; and

m a is about 0.35 to about 0.55; and n a is 1−m a ;

wherein the copolymer has a degree of polymerization of about 5 to about 25.

11 . The random copolymer of claim 10 , wherein:

R 1a and R 2a are independently methyl;

R 3a , R 4a , and R 5a are independently hydrogen or methyl;

R 6a is methyl or ethyl;

R 7a is C 1-4 alkyl, e.g., methyl, ethyl, propyl, or butyl;

p 1a is 1 or 2;

p 2a is 1, 2 or 3;

m a is about 0.35 to about 0.55; and n a is 1−m a .

12 . The random copolymer of claim 10 , wherein the random copolymer is of Formula IIIb:

or an acceptable salt or solvate thereof, wherein:

m b is about 0.45 to about 0.55; n b is 1−m b ; and

the degree of polymerization is about 5 to about 10.

13 . The random copolymer of claim 10 , wherein the random copolymer is of Formula IIIc:

or an acceptable salt or solvate thereof, wherein:

m c is about 0.35 to about 0.45; n c is 1−m c ; and

the degree of polymerization is about 5 to about 10.

14 . The random copolymer of claim 10 , wherein the random copolymer is of Formula IIId:

or an acceptable salt or solvate thereof, wherein:

m d is about 0.45 to about 0.55; n d is 1−m d ; and

the degree of polymerization is about 5 to about 10.

15 . The random copolymer of claim 10 , wherein the random copolymer is of Formula IIIe:

or an acceptable salt or solvate thereof, wherein:

m e is about 0.50 to about 0.60; n e is 1−m e ; and

the degree of polymerization is about 5 to about 10.

16 . A pharmaceutical composition comprising the random copolymer of claim 1 and a pharmaceutically acceptable carrier or diluent.

17 . A method of treating a microbial infection in an animal in need thereof, said method comprising administering to the animal an effective amount of the pharmaceutical composition of claim 16 .

18 . The method of claim 17 , wherein the microbial infection is an oral infection.

19 . The method of claim 17 , wherein the microbial infection is a bacterial infection, a fungal infection, or a viral infection.

20 . A method of killing or inhibiting the growth of a microorganism, said method comprising contacting the microorganism with an effective amount of the random copolymer of claim 1 .

21 . The method of claim 20 , wherein the microorganism is a bacterial cell, a fungus, or a virus.

22 . The method of claim 20 , wherein the random copolymer is present on a substrate.

23 . The method of claim 22 , wherein the random copolymer is covalently attached to the substrate.

24 . The method of claim 22 , wherein the substrate is selected from the group consisting of wood, synthetic polymers, natural fibers, synthetic fibers, cloth, paper, rubber and glass.

25 . An antimicrobial composition comprising the copolymer of claim 1 and a composition selected from the group consisting of paints, lacquers, coatings, varnishes, caulks, grouts, adhesives, resins, films, cosmetics, soaps, lotions, handwashes, and detergents.

26 . A method of providing an antidote to low molecular weight heparin overdose in an animal, said method comprising administering to the animal the pharmaceutical composition of claim 16 .

27 . A random copolymer having a monomer unit of Formula I:

—[CH 2 —C(R 1 )(B 1 )] n —  I

wherein:

R 1 is hydrogen or C 1-4 alkyl;

B 1 is -X 1 -Y 1 -Z 1 , wherein:

X 1 is carbonyl (—C(═O)—) or optionally substituted C 1-6 alkylene; or X 1 is absent;

Y 1 is O, NH, or optionally substituted C 1-6 alkylene; or Y 1 is absent;

Z 1 is -Z 1A -Z 1B , wherein:

Z 1A is alkylene, arylene, or heteroarylene, any of which is optionally substituted; or Z 1A is absent;

Z 1B is -guanidino, -amidino, —N(R 3 )(R 4 ) or —N + (R 3 )(R 4 )(R 5 ), wherein R 3 , R 4 , and R 5 are independently hydrogen, alkyl, aminoalkyl, aryl, heteroaryl, heterocyclic, or aralkyl; or

Z 1 is pyridinium

 or phosphonium

 wherein R 8 , R 91 ,

R 92 , and R 93 are independently hydrogen or alkyl;

n is 1−m, wherein m is as defined below;

and a monomer unit of Formula II:

—[CH 2 —C(R 2 )(D 2 )] m —  II

or an acceptable salt or solvate thereof,

wherein:

R 2 is hydrogen or C 1-4 alkyl;

D 2 is —X 2 -Y 2 -Z 2 , wherein

X 2 is carbonyl (—C(═O)—) or optionally substituted C 1-6 alkylene, or X 2 is absent;

Y 2 is O, NH, or optionally substituted C 1-6 alkylene, or Y 2 is absent;

Z 2 is alkyl, cycloalkyl, alkoxy, aryl, or aralkyl, any of which is optionally substituted; and

m is about 0.1 to about 0.9;

wherein the copolymer has a degree of polymerization of about 5 to about 50; and

wherein a chain transfer agent A is used to control the degree of polymerization of the random copolymer.

28 . The random copolymer of claim 27 , wherein the chain transfer agent A is

or an alkoxycarbonylalkylthiol.

29 . The random copolymer of claim 28 , wherein the chain transfer agent A is