Extremely Fast Hydrogen Atom Transfer between Nitroxides and HOO · Radicals and Implication for Catalytic Coantioxidant Systems

We report a novel coantioxidant system based on TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) that, in biologically relevant model systems, rapidly converts chain carrying alkylperoxyl radicals to HOO center dot. Extremely efficient quenching of HOO center dot by TEMPO blocks the oxidative chain. Rate constants in chlorobenzene were measured to be 1.1 x 10(9) M-1 s(-1) for the reductive reaction TEMPO + HOO center dot -> TEMPOH + O-2 and 5.0 x 10(7) M-1 s(-1) for the oxidative reaction TEMPOH + HOO center dot -> + TEMPO + H2O2. These rate constants are significantly higher than that associated with the reaction of HOO center dot with alpha-tocopherol, Nature's best lipid soluble antioxidant (k = 1.6 x 10(6) M-1 s(-1)). These data show that in the presence of ROO center dot-to-HOO center dot chain-transfer agents, which are common in lipophilic environments, the TEMPO/TEMPOH couple protects organic molecules from oxidation by establishing an efficient reductive catalytic cycle. This catalytic cycle provides a new understanding of the efficacy of the antioxidant capability of TEMPO in nonaqueous systems and its potential to act as a chemoprotective against radical damage.