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

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=1.5×10⁷ and 1.1×10⁵  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.