Combined experimental and theoretical studies of the structure-antiradical activity relationship of heterocyclic hydrazone compounds

The present paper describes combined experimental and theoretical studies of twelve heterocyclic compounds bearing hydrazone functional group (1–12). Experimentally, the free radical scavenging activity of all the compounds have been investigated using DPPH, ABTS, and DMSO alkaline assays. The obtained results showed that these compounds are potent antiradical agents. The best results have been obtained with the imidazole derivatives 5 and 12, which showed higher antiradical activity than the BHT standard in DPPH and ABTS assays. Theoretical calculations, by means of DFT/B3LYP approach, were carried out in order to explain the experimental results. Some structural characteristics such as molecular descriptors, highest occupied molecular orbital, and molecular electrostatic potential mapping have been computed. The mechanisms, HAT (hydrogen atom transfer), SETPT (sequential electron transfer proton transfer), and SPLET (sequential proton loss electron transfer) have been studied and discussed. In addition, the reactions toward HO•, MeO•, HOO•, and MeOO• radicals have been investigated. As results, the radical scavenger properties of the studied compounds were confirmed. The HAT was found to be the thermodynamically dominant mechanism in the gas-phase for all the studied compounds, whereas the SPLET mechanism is the thermodynamically favorable pathway in ethanol. A good correlation with DPPH and ABTS assays was found between experimental and theoretical results. [Display omitted] •The antiradical activity of twelve heterocyclic hydrazone compounds has been studied.•DPPH, ABTS, and DMSO alkaline assays were employed to investigate the in vitro antiradical activity.•DFT calculations of the antiradical mechanisms have been performed.•The reactions with typical reactive oxygen species have been investigated.