Degradable crosslinkers, and degradable crosslinked hydrogels comprising them

1. A crosslinked hydrogel, comprising a hydrophilic polymer; and a crosslinker selected from the group consisting of a compound of formula 1 and a compound of formula 2, wherein said compound of formula 1 is represented by:

wherein

X represents independently for each occurrence O or S;

L represents independently for each occurrence —NH—O—Q, or —O—NH—Q;

Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;

R represents independently for each occurrence H or alkyl;

Z represents (CR 2 ) n ,(CR 2 ) n J(CR 2 ) m , or (CR 2 ) n Ar(CR 2 ) m ;

Ar represents independently for each occurrence aryl or heteroaryl;

J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;

n represents independently for each occurrence an integer in the range 1–10; and

m represents independently for each occurrence an integer in the range 0–10; and

said compound of formula 2 is represented by:

wherein

X represents independently for each occurrence O or S;

M represents independently for each occurrence —NH—O—Q, or —O—NH—Q;

Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;

R represents independently for each occurrence H or alkyl;

Z represents (CR 2 ) n , (CR 2 ) n J(CR 2 ) m , or (CR 2 ) n Ar(CR 2 ) m ;

Ar represents independently for each occurrence aryl or heteroaryl;

J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;

G represents (CR (4−t) ), aryl, or heteroaryl;

n represents independently for each occurrence an integer in the range 1–10; and

t represents 3 or 4.

2. The crosslinked hydrogel of claim 1 , wherein said hydrophilic polymer comprises an acrylic acid, acrylate, or acrylamide.

3. The crosslinked hydrogel of claim 1 , wherein said hydrophilic polymer comprises acrylic acid, 2-hydroxyethyl acrylate, oligo(ethylene glycol) 2-methacrylate, acrylamide, N,N-dimethylacrylamide, or N-(tris(hydroxymethyl)methyl)acrylamide.

4. The crosslinked hydrogel of claim 1 , wherein said hydrophilic polymer consists of a first acrylamide and a second acrylamide.

5. The crosslinked hydrogel of claim 4 , wherein said first acrylamide is acrylamide or N,N-dimethylacrylamide.

6. The crosslinked hydrogel of claim 4 , wherein said second acrylamide is N-(tris(hydroxymethyl)methyl)acrylamide.

7. The crosslinked hydrogel of claim 4 , wherein said first acrylamide is acrylamide or N,N-dimethylacrylamide; and said second acrylamide is N-(tris(hydroxymethyl)methyl)acrylamide.

8. The crosslinked hydrogel of claim 4 , wherein said hydrophilic polymer consists of an acrylamide and an acrylate.

9. The crosslinked hydrogel of claim 8 , wherein said acrylamide is acrylamide or N,N-dimethylacrylamide.

10. The crosslinked hydrogel of claim 8 , wherein said acrylate is acrylic acid, 2-hydroxyethyl acrylate, or oligo(ethylene glycol) 2-methacrylate.

11. The crosslinked hydrogel of claim 8 , wherein said acrylamide is acrylamide or N,N-dimethylacrylamide; and said acrylate is acrylic acid, 2-hydroxyethyl acrylate, or oligo(ethylene glycol) 2-methacrylate.

12. The crosslinked hydrogel of claim 1 , wherein said hydrophilic polymer consists of a first acrylate and a second acrylate.

13. The crosslinked hydrogel of claim 12 , wherein said first acrylate is acrylic acid, 2-hydroxyethyl acrylate, or oligo(ethylene glycol) 2-methacrylate.

14. The crosslinked hydrogel of claim 12 , wherein said first acrylate is acrylic acid, 2-hydroxyethyl acrylate, or oligo(ethylene glycol) 2-methacrylate; and said second acrylate is acrylic acid, 2-hydroxyethyl acrylate, or oligo(ethylene glycol) 2-methacrylate.

15. A method of preparing a crosslinked hydrogel, comprising a hydrophilic polymer and a crosslinker represented by 1:

wherein

X represents independently for each occurrence O or S;

L represents independently for each occurrence —NH—O—Q, or —O—NH—Q;

Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO (CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;

R represents independently for each occurrence H or alkyl;

Z represents (CR 2 ) n , (CR 2 ) n J(CR 2 ) m , or (CR 2 ) n Ar(CR 2 ) m ;

Ar represents independently for each occurrence aryl or heteroaryl;

J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O ) n , or (CH 2 CH 2 N(R)) n ;

n represents independently for each occurrence an integer in the range 1–10; and

m represents independently for each occurrence an integer in the range 0–10;

comprising:

a) reacting a monomer represented by 1 with a hydrophilic monomer in the presence of an initiator.

16. A method of preparing a crosslinked hydrogel, comprising a hydrophilic polymer and a crosslinker represented by 2:

wherein

X represents independently for each occurrence O or S;

M represents independently for each occurrence —NH—O—Q, or —O—NH—Q;

Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;

R represents independently for each occurrence H or alkyl;

Z represents (CR 2 ) n , (CR 2 ) n J(CR 2 ) m , or (CR 2 ) n Ar(CR 2 ) m ;

Ar represents independently for each occurrence aryl or heteroaryl;

J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O ) n , or (CH 2 CH 2 N(R)) n ;

G represents (CR (4−t) ), aryl, or heteroaryl;

n represents independently for each occurrence an integer in the range 1–10; and

t represents 3 or 4;

comprising:

a) reacting a monomer represented by 1 with a hydrophilic monomer in the presence of an initiator.

17. The crosslinked hydrogel of claim 1 , wherein said crosslinker is said compound of formula 1.

18. The crosslinked hydrogel of claim 17 , wherein X represents O.

19. The crosslinked hydrogel of claim 17 , wherein L represents —NH—O—Q.

20. The crosslinked hydrogel of claim 17 , wherein L represents —O—NH—Q.

21. The crosslinked hydrogel of claim 17 , wherein Q represents acryloyl, or 2-methacryloyl.

22. The crosslinked hydrogel of claim 17 , wherein R represents H.

23. The crosslinked hydrogel of claim 17 , wherein Z represents (CR 2 ) n .

24. The crosslinked hydrogel of claim 17 , wherein X represents O; and L represents —NH—O—Q.

25. The crosslinked hydrogel of claim 17 , wherein X represents O; and L represents —O—NH—Q.

26. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —NH—O—Q; and Q represents acryloyl, or 2-methacryloyl.

27. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —O—NH—Q; and Q represents acryloyl, or 2-methacryloyl.

28. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —NH—O—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.

29. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.

30. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —NH—O—Q; Q represents acryloyl, or 2-methacryloyl; R represents H; and Z represents (CR 2 ) n .

31. The crosslinked hydrogel of claim 17 , wherein X represents O; L represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; R represents H; and Z represents (CR 2 ) n .

32. The crosslinked hydrogel of claim 1 , wherein said crosslinker is said compound of formula 2.

33. The crosslinked hydrogel of claim 32 , wherein X represents O.

34. The crosslinked hydrogel of claim 32 , wherein M represents —NH—O—Q.

35. The crosslinked hydrogel of claim 32 , wherein M represents —O—NH—Q.

36. The crosslinked hydrogel of claim 32 , wherein Q represents acryloyl, or 2-methacryloyl.

37. The crosslinked hydrogel of claim 32 , wherein R represents H.

38. The crosslinked hydrogel of claim 32 , wherein X represents O; and M represents —NH—O—Q.

39. The crosslinked hydrogel of claim 32 , wherein X represents O; and M represents —O—NH—Q.

40. The crosslinked hydrogel of claim 32 , wherein X represents O; M represents —NH—O—Q; and Q represents acryloyl, or 2-methacryloyl.

41. The crosslinked hydrogel of claim 32 , wherein X represents O; M represents —O—NH—Q; and Q represents acryloyl, or 2-methacryloyl.

42. The crosslinked hydrogel of claim 32 , wherein X represents O; M represents —NH—O—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.

43. The crosslinked hydrogel of claim 32 , wherein X represents O; M represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.