Antioxidant Polymers with Phenolic Pendants for the Mitigation of Cellular Oxidative Stress.

Overproduction of reactive oxygen species (ROS) in cells is a major health concern as it may lead to various diseases through oxidative damage of biomolecules. Commonly used traditional small molecular antioxidants (polyphenols, carotenoids, vitamins, etc.) have inadequate efficacy in lowering excessive levels of ROS due to their poor aqueous solubility and bioavailability. In response to the widespread occurrence of antioxidant polyphenols in various biorenewable resources, we aimed to develop water-soluble antioxidant polymers with side chain phenolic pendants. Four different types of copolymers (-) containing phenyl rings with different numbers of hydroxy (-OH) substituents (0: phenylalanine, 1: tyrosyl, 2: catechol, or 3: gallol) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization with a desired molar mass (8500-10000 g/mol) and a narrow dispersity ( ≤ 1.3). After successful characterizations of -, their antioxidant properties were analyzed by different methods, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino--3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 4,4'-diamino-3,3',5,5'-tetramethylbiphenyl (TMB), and β-carotene (βC) assays. Our results revealed that the gallol pendant polymers can effectively scavenge ROS. Furthermore, electron paramagnetic resonance (EPR) spectroscopy with DPPH also confirmed the radical quenching ability of the synthesized polymers. The gallol pendant polymers, at a well-tolerated concentration, could effectively penetrate the macrophage cells and restore the HO-induced ROS to the basal level. Overall, the present approach demonstrates the efficacy of water-soluble antioxidant polymers with gallol pendants toward the mitigation of cellular oxidative stress.