Multi-armed, monofunctional, and hydrolytically stable derivatives of poly(ethylene glycol) and related polymers for modification of surfaces and molecules

A method for preparing a branched, monofunctional, water-soluble polymer, the method comprising:

• (i) reacting a monomethoxypoly(ethylene glycol)polymer comprising a single reactive moiety, W, and having the structure mPEG-W, where W is the single reactive moiety, with a linker molecule comprising from 1 to 10 carbon atoms and having the structure X—C(Y)(R)—Z,
• where X and Y each independently comprise reactive groups that can react with W to form hydrolytically stable linkage fragments P and Q, respectively,
• Z is a moiety that (a) comprises a single ionizable reactive site that is capable of reacting with ion exchange chromatography media, and (b) is not reactive with either X or Y, and
• R is H, methyl or another alkyl group,
• under conditions effective to provide an impure branched monofunctional, water-soluble polymer having the structure:
• “mPEG-P—C(R)(Z)-Q-mPEG”, and one or more polymeric impurities, where neither the linker molecule nor the resulting linkage fragments P or Q comprises aromatic or ester groups, and
• (ii) purifying the impure branched monofunctional, water-soluble polymer from step (i) by ion exchange chromatography under conditions effective to essentially remove the polymeric impurities to thereby provide purified mPEG-P—C(R)(Z)-Q-mPEG in essentially pure form.