Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity?

Abstract

Model phenoxyl and more complex flavonoid radicals were generated by azide radical induced one-electron oxidation in aqueous solutions. Spectral, acid–base and redox properties of the radicals were investigated by the pulse radiolysis technique. The physicochemical characteristics of the flavonoid radicals closely match those of the ring with the lower reduction potential. In flavonoids which have a 3,5-dihydroxyanisole (catechins), or a 2,4-dihydroxyacetophenone (hesperidin, rutin, quercetin)-like A ring and a catechol- or 2-methoxyphenol-like B ring, the antioxidant active moiety is clearly the B ring [reduction potential difference between the model phenoxyls is ΔE(A–B ring models) > 0.1 V]. In galangin, where the B ring is unsubstituted phenyl, the antioxidant active moiety is the A ring. Even though the A ring is not a good electron donor, E₇ > 0.8/NHE V, it can still scavenge alkyl peroxyl radicals, E₇= 1.06 V, and the superoxide radical, E₇ > 1.06 V. Quercetin is the best electron donor of all investigated flavonoids (measured E_10.8= 0.09 V, and calculated E₇= 0.33 V). The favourable electron-donating properties originate from the electron donating 0-3 hydroxy group in the C ring, which is conjugated to the catechol (B ring) radical through the 2,3-double bond. The conjugation of the A and B rings is apparently minimal, amounting to less than 2.5% of the substituent effect in either direction. Thus, neglecting the acid–base equilibria of the A ring, and using those of the B ring and the measured values of the reduction potentials at pH 3, 7 and 13.5, the pH dependence of the reduction potentials of the flavonoid radicals can be calculated. In neutral and slightly alkaline media (pH 7–9), all investigated flavonoids are inferior electron donors to ascorbate. Quercetin, E₇= 0.33 V, and gallocatechins, E₇= 0.43 V, can reduce vitamin E radicals (assuming the same reduction potential as Trolox C radicals, E₇= 0.48 V). Since all investigated flavonoid radicals have reduction potentials lower than E, =1.06 V of alkyl peroxyl radicals, the parent flavonoids qualify as chain-breaking antioxidants in any oxidation process mediated by these radicals.