The hydroperoxyl antiradical activity of natural chalcones in physiological environments: Theoretical insights into the mechanism, kinetics and pH effects

Chalcones (CHA), based on the 1,3-diaryl-2-propen-1-one structure, are flavonoids with an open chain. Wide-ranging biological effects of CHA have been observed, including tyrosinase inhibition, anticancer, anti-inflammatory, and antioxidant activities. However, the physical chemistry of the antiradical activity of these compounds has not been explored in depth. We report an investigation on the mechanisms and kinetics of CHA's activity in scavenging hydroperoxyl radicals using calculations based on density functional theory (DFT). It was found that the studied CHA possess powerful HOO center dot radical scavenging properties. In a lipid-like medium, CHA react with HOO center dot via the hydrogen transfer reaction with k = 103 -105 M-1 s- 1, while in an aqueous solution, the activity is defined by the anion states according to the single electron transfer (SET) pathway, yielding a rate constant of k = 106 -108 M-1 s- 1. The rate constants are sensitive to the protonation state and hence vary with pH showing the highest HOO center dot radical scavenging activity at pH = 7.3-7.5. In the examined media, calculations suggest that CHA can have stronger HOO center dot antiradical activity than Trolox, with kinetics comparable to ascorbic acid or resveratrol.