Insights into the complexation and oxidation of quercetin and luteolin in aqueous solutions in presence of selected metal cations

Flavonoids are natural antioxidants that can be used for the chelation of metal ions to treat metal toxicity. Ideal chelators should form stable metal complexes and be resistant to oxidative degradation reactions in aqueous solutions at physiological conditions (pH 7.4 and 37 °C). In this work, the complexation and oxidation of quercetin and luteolin with selected metal cations (i.e. Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Al(III)) in aqueous solutions at pH 4 and 7.4 is discussed. Using UV–Vis, RP-UHPLC-PDA-MS, ESI-MS and 1H NMR, information about the complexing ability, stoichiometry, and the preferred metal binding sites was obtained. At pH 7.4, all metal ions were complexed by luteolin and quercetin, whereas at pH 4 both flavonoids only formed complexes with the trivalent metal cations (i.e. Cr(III), Fe(III), and Al(III)). No clear preference for any of the complexation sites was observed for quercetin and luteolin. UV–Vis and RP-UHPLC-PDA-MS showed that, at pH 7.4, chelation of quercetin was followed by metal-mediated oxidation resulting in degradation of quercetin. On the contrary, luteolin complexes with metal cations were stable and no oxidative degradation of luteolin was observed. The oxidative degradation pathway of quercetin was investigated by incubation in H218O, which showed that the oxidation occurs via both oxygenation and hydroxylation mechanisms, the latter being the preferred pathway for the trivalent metal ions. Our results indicate that luteolin is a more suitable chelating agent of Al(III) and first-row transition metal cations due to its higher oxidative stability and its ability to form stable complexes in aqueous solutions at pH 7.4.