Ligand-based design of chalcone analogues and thermodynamic analysis of their mechanism of free radical scavenge.

Overproduction of free radicals in the body may result in oxidative stress, which plays an active role in the development of various health disorders. Consequently, the development of efficient free radical scavengers and evaluation of their antioxidant properties is a research area of interest. In the present research, computational quantum chemical approach based on the density functional theory (DFT) method was employed to elucidate the free radical scavenge of chalcone derivatives via thermodynamic studies. New set of chalcone antioxidants were designed. Their reactivity towards hydroperoxyl (HOO·) and methyl peroxyl (CH3OO·) radicals were investigated through systematic study of their mechanism of free radical scavenge. Various reaction enthalpies and Gibbs free energy that characterize the various steps in these mechanisms were computed in the gas phase and aqueous solution, in order to identify the main channels of reaction. Results in the gas phase indicate that hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms represent the most plausible reaction pathways, while single electron transfer followed by proton transfer (SET-PT) mechanism was thermodynamically unfeasible. However, these mechanisms were thermodynamically favoured in aqueous solution. Also, these chalcone derivatives were observed to be more effective in scavenging HOO· than CH3OO· radicals in both phases. Based on the exergonicity of the obtained results, the molecule MCHM 17 ((E)-1-(3-bromo-5-hydroxyphenyl)-3-(2,5-dihydroxyphenyl)prop-2-en-1-one) at the 5-OH site was found to exhibit the greatest potential to scavenge HOO· and CH3OO· radicals in both phases. This research is a gateway to the efficient exploitation of these compounds in pharmacy and food chemistry.