Hydroxychalcones as potent antioxidants: Structure–activity relationship analysis and mechanism considerations

Hydroxychalcones (1–6) with different numbers and positions of hydroxyl groups on the two aromatic rings were synthesised, and their antioxidant activities against the stable galvinoxyl (GO) radical in ethanol and ethyl acetate, and free radical-mediated lipid peroxidation of human red blood cells and DNA strand breakage were systematically examined. Kinetic analysis of the GO-scavenging reaction and the quantum chemical calculations of O–H bond dissociation enthalpy (BDE) demonstrate that the molecular structure and the reaction medium are two important factors affecting the antioxidant mechanism and activity. In ethanol, that supports ionisation, the antioxidant reaction of the compounds (1, 2 and 3), bearing o-dihydroxyl groups, occurs primarily by sequential proton loss electron transfer (SPLET mechanism) while, in ethyl acetate, the reaction mechanism is predominantly direct hydrogen atom transfer (HAT mechanism). For the other compounds (4, 5 and 6), in both ethyl acetate and ethanol, the reaction mechanism is only HAT.