Interactions of quercetin with iron and copper ions: Complexation and autoxidation

Abstract

Quercetin (3,3′,4′,5,7-pentahydroxyflavone), one of the most abundant dietary flavonoids, has been investigated for its ability to bind FeII, FeIII, CuI and CuII in acidic to neutral solutions. In particular, analysis by UV–visible spectroscopy allows to determine the rate constants for the formation of the 1:1 complexes. In absence of added metal ion, quercetin undergoes a slow autoxidation in neutral solution with production of low hydrogen peroxide (H2O2) concentrations. Autoxidation is accelerated by addition of the metal ions according to: CuI > CuII≫FeII ≈ FeIII. In fact, the iron-quercetin complexes seem less prone to autoxidation than free quercetin in agreement with the observation that EDTA addition, while totally preventing iron-quercetin binding, slightly accelerates quercetin autoxidation. By contrast, the copper-quercetin complexes appear as reactive intermediates in the copper-initiated autoxidation of quercetin. In presence of the iron ions, only low concentrations of H2O2 can be detected. By contrast, in the presence of the copper ions, H2O2 is rapidly accumulated. Whereas FeII is rapidly autoxidized to FeIII in the presence or absence of quercetin, CuI bound to quercetin or its oxidation products does not undergo significant autoxidation. In addition, CuII is rapidly reduced by quercetin. By HPLC-MS analysis, the main autoxidation products of quercetin are shown to be the solvent adducts on the p-quinonemethide intermediate formed upon two-electron oxidation of quercetin. Finally, in strongly acidic conditions (pH 1–2), neither autoxidation nor metal complexation is observed but FeIII appears to be reactive enough to quickly oxidize quercetin (without dioxygen consumption). Up to ca. 7 FeIII ions can be reduced per quercetin molecule, which points to an extensive oxidative degradation.