Facile Synthesis of Innocuous Comb-Shaped Polymethacrylates with PEG Side Chains by Nitroxide-Mediated Radical Polymerization in Hydroalcoholic Solutions

The nitroxide-mediated copolymerization of poly(ethylene glycol) methyl ether methacrylate (MePEGMA) with a small amount of acrylonitrile using an SG1-based alkoxyamine initiator was shown to be a very simple and efficient technique to synthesize graft copolymers with poly(ethylene glycol) side chains. The copolymerizations were carried out in ethanol/water solutions as environmentally friendly media. Following our observation that the rate increased with the proportion of water, a polymerization temperature as low as 71 °C could be used for a water content of 75%, which conferred great flexibility to the process. The so-formed copolymers were living, with high crossover efficiency toward block copolymers. Importantly, following a cytotoxicity study over three different cell lines that represent important mammalian cell types, these polymers were shown to be noncytotoxic even at very high doses without any other purification step than a simple precipitation. These comb-shaped PEG-based polymers may represent an ideal platform for the synthesis of PEGylating moieties for proteins and nanoparticles intended to be used in the biomedical field.