Redox properties of individual quercetin moieties

• Published in: Free radical biology & medicine Vol. 143; pp. 240 - 251
• Main Authors: Heřmánková, Eva, Zatloukalová, Martina, Biler, Michal, Sokolová, Romana, Bancířová, Martina, Tzakos, Andreas G., Křen, Vladimír, Kuzma, Marek, Trouillas, Patrick, Vacek, Jan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019
• Subjects: Antiradical properties; Benzofuranone; Electron transfer; Electronic structure; Quercetin oxidation; Redox properties; Stability; Electronic structure; Stability; Benzofuranone; Quercetin oxidation; Electron transfer; Antiradical properties; Redox properties
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2019.08.001

Quercetin is one of the most prominent and widely studied flavonoids. Its oxidation has been previously investigated only indirectly by comparative analyses of structurally analogous compounds, e.g. dihydroquercetin (taxifolin). To provide direct evidence about the mechanism of quercetin oxidation, we employed selective alkylation procedures for the step-by-step blocking of individual redox active sites, i.e. the catechol, resorcinol and enol C-3 hydroxyls, as represented by newly prepared quercetin derivatives 1–3. Based on the structure-activity relationship (SAR), electrochemical, and computational (density functional theory) studies, we can clearly confirm that quercetin is oxidized in the following steps: the catechol moiety is oxidized first, forming the benzofuranone derivative via intramolecular rearrangement mechanism; therefore the quercetin C-3 hydroxy group cannot be involved in further oxidation reactions or other biochemical processes. The benzofuranone is oxidized subsequently, followed by oxidation of the resorcinol motif to complete the electrochemical cascade of reactions. Derivatization of individual quercetin hydroxyls has a significant effect on its redox behavior, and, importantly, on its antiradical and stability properties, as shown in DPPH/ABTS radical scavenging assays and UV–Vis spectrophotometry, respectively. The SAR data reported here are instrumental for future studies on the oxidation of biologically or technologically important flavonoids and other polyphenols or polyhydroxy substituted aromatics. This is the first complete and direct study mapping redox properties of individual moieties in quercetin structure. [Display omitted] •Quercetin (Q) contains redox-active centers undergoing oxidative transformation.•Three-step oxidation of Q is accompanied by specific adsorption processes.•Benzofuranone intermediate exclusively participates in oxidation reaction cascade of Q.•After catechol moiety oxidation, C3–OH can not contribute to Q biological activities more.•The first SAR insight into Q redox behavior based on selective alkylation is described.