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

Quercetin (3,3′,4′,5,7-pentahydroxyflavone), one of the most abundant dietary flavonoids, has been investigated for its ability to bind Fe^II, Fe^III, Cu^I and Cu^II 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: Cu^I > Cu^II ≫ Fe^II ≈ Fe^III. 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, H₂O₂is rapidly autoxidized to Fe^III in the presence or absence of quercetin, Cu^I bound to quercetin or its oxidation products does not undergo significant autoxidation. In addition, Cu^II 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 Fe^III appears to be reactive enough to quickly oxidize quercetin (without dioxygen consumption). Up to ca. 7 Fe^III ions can be reduced per quercetin molecule, which points to an extensive oxidative degradation.