Structure-Activity and Structure-Mechanism Relationships for the Radical-Scavenging Reaction of Flavonols

Flavonols show an efficient scavenging activity against reactive oxygen radicals. However, the detailed mechanism has yet to be fully clarified. There are two mechanism for the radical-scavenging reactions of phenolic antioxidants, i.e., one-step hydrogen-atom transfer (HAT) and electron transfer followed by proton transfer (ET-PT). In this study, we discuss the radical-scavenging mechanism for 6 flavonols, which are myricetin (Myr), quercetin (Que), kaempferol (Kae), and 3 methylated quercetin analogs (2’-MeQue, 5’-MeQue, and Me2Que), based on the relationships between the scavenging rate constants (k) against galvinoxyl radical and thermodynamic parameters, such as O-H bond dissociation energies (DHT) and ionization potentials (IP), calculated by the density functional theory (DFT).The k values were determined in deaerated acetonitrile at 298 K by a stopped-flow technique. DFT calculations were carried out at the B3LYP/6-31G(d) level.The k value increases in the order: Que < 2’-MeQue ≈ Kae < Me2Que < Myr < 5’-MeQue. The plot of the logarithm of the k values (log k) vs. DHT or IP values revealed that the log k values for 5’-MeQue, Myr, Me2Que, and Que are linearly correlated with their IP values. These results suggest that the radical-scavenging reaction by these 4 flavonols may proceeds via the ET-PT mechanism.The 9th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia