Antioxidant Polymers via the Ugi Reaction for In Vivo Protection of UV-Induced Oxidative Stress

Small-molecule antioxidants perform poorly in vivo in combating oxidative stress because of their low bioavailability. Water-soluble polymeric antioxidants can overcome the limitations of small molecular antioxidants (instability, poor water solubility, fast metabolism, etc.), but there are only a few efficient synthesis methods to prepare safe and effective polymeric antioxidants. In this study, we develop a series of antioxidant polymers containing ferrocene and/or indole moieties through the Ugi four-component reaction and simple free radical polymerization. These polymers are screened using different criteria to find a biocompatible antioxidative polymer that effectively inhibits the lethal and teratogenic effects of UV-induced oxidative damage on zebrafish embryos. This study identifies a strategy to use antioxidative polymers in vivo, demonstrates the value of multicomponent reactions in interdisciplinary areas, and provides the underlying insights to guide the design of antioxidant polymeric biomaterials.