Antioxidant Polymers via the Kabachnik-Fields Reaction to Control Cellular Oxidative Stress

Small molecular antioxidants are almost ineffective in regulating harmful oxidative stress in vivo because of their poor bioavailability. Polymer antioxidants are a promising alternative to address this issue, but their laborious synthetic routes limit their development. In this study, aliphatic and aromatic aldehydes are used to synthesize a family of polymers containing different alpha-aminophosphonate pendant groups via a facile one-pot method that combines the Kabachnik-Fields (KF) reaction and free radical polymerization. The structure-property relationship study of these polymers reveals the KF moieties in polymer structures confer radical scavenging ability on polymers. The radical scavenging ability and cytotoxicity of these polymers are evaluated in a stepwise manner to identify a biocompatible polymer antioxidant that can effectively protect the cells from H2O2-induced oxidative damage. This is the first attempt to develop antioxidative polymers by the KF reaction. It highlights the feasibility of synthesizing new functional polymers using multicomponent reactions, which has important implications for organic and polymer chemistry.