Insights into the mechanisms and kinetics of the hydroperoxyl radical scavenging activity of Artepillin C

Artepillin C (AC) is a natural prenylated phenolic compound present in propolis produced by honey bees in Brazil, which was reported to exhibit a variety of biological activities. In the present study we report a systematic thermodynamic and kinetic investigation on the hydroperoxyl (HOO) scavenging activity and mechanism of AC using DFT calculations. Different reaction mechanisms have been investigated at all the possible active sites of AC in the gas phase and in physiological environments. Based on the results, AC is predicted to exhibit excellent HOO radical scavenging in aqueous solution with k(overall) = 7.44 x 10(7) M-1 s(-1). Its activity is significantly lower in the gas phase and lipid environment. Single electron transfer was found to be the main antiradical mechanism in the aqueous solution at pH = 7.4, dominated by the dianion state of AC. The overall rate coefficient of HOO radical scavenging of AC in water is about 572 times higher than that of Trolox. This suggests that AC is a potent HOO radical scavenger in water.