Fast reaction of carbon free radicals with flavonoids and other aromatic compounds.

ABSTRACT

Many theoretical and experimental studies have shown that the principal initial biological targets of free radicals are nucleic acids, lipids and proteins. The reaction normally generates carbon-centered radicals which can propagate molecular damage either directly or after formation of new reactive species following reaction with oxygen. Overall damage prevention is therefore best achieved by repair of the carbon radicals before they initiate further reactions. Recent studies have shown that the repair cannot be achieved by normal levels of the endogenous antioxidants glutathione, ascorbate or urate. Since their concentrations are well regulated and cannot be enhanced by oral intake, we have investigated the effectiveness of flavonoids and other polyphenols as potential carbon radical repair agents, because their levels in vivo can be significantly enhanced by diet. Pulse radiolysis measurements of the rate constants of repair of amino acid radicals by several polyphenols showed reversible formation of radical-polyphenol adducts 100-1000 times faster than previously reported for the bimolecular stoichiometric reactions of flavonoids i.e. with rate constants in the order of 1010 M-1s-1. Adduct formation depended only on the presence of a carbon-centered radical and an aromatic moiety in the reactants, without the involvement of redox reactions at the phenolic groups. Formation of adducts lowered the reactivity of the radicals. Our results suggest that flavonoids, polyphenols and many of their metabolites can effectively reduce the damaging potential of carbon radicals at concentrations achievable in vivo by diets rich in fruits and vegetables.