Keto-Functionalized Polymer Scaffolds as Versatile Precursors to Polymer Side-Chain Conjugates

A new methacrylate monomer with a reactive ketone side chain, 2-(4-oxopentanoate)ethyl methacrylate (PAEMA), was synthesized and subsequently polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization to give a polymer with a narrow molecular weight distribution (PDI = 1.25). The polymer was chain extended with poly(ethylene glycol methyl ether methacrylate) (PEGMA) to yield a block copolymer. Aminooxy-containing small molecules and oligoethylene glycol were conjugated to the ketone functionality of the side chains in high yields. Cytotoxicity of the oxime-linked tetra(ethylene glycol) polymer to mouse fibroblast cells was investigated; the polymer was found to be noncytotoxic up to 1 mg/mL. The ease with which this polymer is functionalized suggests that it may be useful in forming tailored polymeric medicines.