A DFT Study on the Kinetics of HOO•, CH3OO•, and O2•- Scavenging by Quercetin and Flavonoid Catecholic Metabolites

Abstract

Reaction kinetics have been theoretically examined to ascertain the potency of quercetin (Q) and flavonoid catecholic metabolites 1-5 in the inactivation of HOO^•, CH₃OO^•, and O₂^•- under physiological conditions. In lipidic media, the koverallTST/Eck rate constants for the proton-coupled electron transfer (PCET) mechanism indicate the catecholic moiety of Q and 1-5 as the most important in HOO^• and CH₃OO^• scavenging. 5-(3,4-Dihydroxyphenyl)-γ-valerolactone (1) and alphitonin (5) are the most potent scavengers of HOO^• and CH₃OO^•, respectively. The koverallMf rate constants, representing actual behavior in aqueous media, reveal Q as more potent in the inactivation of HOO^• and CH₃OO^• via single electron transfer (SET). SET from 3-O^- phenoxide anion of Q, a structural motif absent in 1-5, represents the most contributing reaction path to overall activity. All studied polyphenolics have a potency of O₂^•- inactivation via a concerted two-proton-coupled electron transfer (2PCET) mechanism. The obtained results indicate that metabolites with notable radical scavenging potency, and more bioavailability than ingested flavonoids, may contribute to human health-promoting effects ascribed to parent molecules.

Keywords: 5-(3,4-dihydroxyphenyl)-γ-valerolactone; alphitonin; catecholic metabolites; density functional theory (DFT); kinetics; peroxyl radicals; quercetin; radical scavenging mechanisms; superoxide.