Degradable crosslinkers, and degradable crosslinked hydrogels comprising them

A compound 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(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
• R represents independently for each occurrence H or alkyl;
• Z represents (CR2)n, (CR2)nJ(CR2)m, or (CR2)nAr(CR2)m;
• Ar represents independently for each occurrence aryl or heteroaryl;
• J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(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.

A method of preparing a compound 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(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
• R represents independently for each occurrence H or alkyl;
• Z represents (CR2)n, (CR2)nJ(CR2)m, or (CR2)nAr(CR2)m;
• Ar represents independently for each occurrence aryl or heteroaryl;
• J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(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 at least 2 molar equivalents of a hydroxylamine with a diester or 2 molar equivalents of an acrylic ester, thereby forming a dihydroxamic acid or 2 moles of a hydroxamic acrylamide, respectively;
• and
• b) reacting said dihydroxamic acid with at least 2 molar equivalents of an acryloyl halide;
• or reacting said 2 moles of a hydroxamic acrylamide with one molar equivalent of an adipoyl chloride.

A method of preparing a compound 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(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
• R represents independently for each occurrence H or alkyl;
• Z represents (CR2)n, (CR2)nJ(CR2)m, or (CR2)nAr(CR2)m;
• Ar represents independently for each occurrence aryl or heteroaryl;
• J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(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 at least 3 molar equivalents of a hydroxylamine with either a triester, a tetraester, or with at least 3 equivalents of an acrylic ester, thereby forming a trihydroxamic acid, a tetrahydroxamic acid, or at least 3 moles of a hydroxamic acrylamide;
• and
• b) reacting said trihydroxamic or tetrahydroxamic acid with at least 3 molar equivalents of an acryloyl halide, or reacting said at least 3 moles of a hydroxamic acrylamide with one molar equivalent of a triacyl halide.