Synthesis of defined high molar mass poly(2-methyl-2-oxazoline)

In this communication, we report for the first time the synthesis of defined high molar mass poly(2-methyl-2-oxazoline) (PMeOx), a water-soluble polymer with excellent anti-fouling properties. So far, there has been no report on low dispersity (D < 1.2) PMeOx longer than 10 kg mol(-1). Higher molar mass would be beneficial for synthesis of polymer-drug conjugates, excipients as well as for other biomedical applications. We report our attempts to prepare defined high molar mass PMeOx via living cationic ring-opening polymerization (CROP) of its monomer using our optimized method that failed due to extensive chain transfer and chain coupling side reactions. Therefore, we proposed an alternative strategy to high molar mass PMeOx based on acetylation of well-defined linear polyethyleneimine (PEI) prepared by controlled side-chain hydrolysis of defined high molar mass PEtOx. This method allowed us to synthesize a series of low-dispersity PMeOx up to 58 kg mol(-1) (D = 1.07). Considering the biomedical potential of PMeOx, the synthesis of such polymers might open a way to a new class of effective polymer-based therapeutics.