Hydrogen Atom Transfer from HOO. to ortho‐Quinones Explains the Antioxidant Activity of Polydopamine

Abstract Melanins are stable and non‐toxic biomaterials with a great potential as chemopreventive agents for diseases connected with oxidative stress, but the mechanism of their antioxidant action is unclear. Herein, we show that polydopamine ( PDA ), a well‐known synthetic melanin, becomes an excellent trap for alkylperoxyl radicals (ROO . , typically formed during autoxidation of lipid substrates) in the presence of hydroperoxyl radicals (HOO . ). The key reaction explaining this peculiar antioxidant activity is the reduction of the ortho ‐quinone moieties present in PDA by the reaction with HOO . . This reaction occurs via a H‐atom transfer mechanism, as demonstrated by the large kinetic solvent effect of the reaction of a model quinone (3,5‐di‐tert‐butyl‐1,2‐benzoquinone) with HOO . ( k =1.5×10 7 and 1.1×10 5 M −1 s −1 in PhCl and MeCN). The chemistry disclosed herein is an important step to rationalize the redox‐mediated bioactivity of melanins and of quinones.