Theoretical evaluation of the antioxidant activity of some stilbenes using the Density Functional Theory

Abstract

In this paper, the antiradical potential of trans-2,4,3′,5′-tetrahydroxystilbene (T-OXY), trans-2,3′,4-trihydroxystilbene (T-RES), cis-2,4,1′,3′-tetrahydroxystilbene (C-OXY) and cis-2,1′,4-trihydroxystilbene (C-RES) is investigated by BDE (E0) and ETS-NOCV calculations, in water, benzene, DMSO, and ethanol. The study of solubility by the COSMO-RS model demonstrates that the compounds are very soluble in DMSO. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms are explored as possible oxidation paths of these compounds using the DFT calculations at B3LYP/6-311++G(2d,2p) level of theory in DMSO. For all the studied compounds, the HAT was found to be the thermodynamically dominant mechanism, indicating that the investigated compounds can be classified according to their antiradical activity in the following sequence order T-OXY˃T-RES˃C-OXY˃C-RES. The evaluation of ΔHBDE reaction enthalpies, ΔHIP, and ΔHPA linked to the three mechanisms with certain radicals (HO·, HOO·, CH3O· and CH3OO·, NO·, and NO2·) are determined. The results indicate the HAT and SPLET mechanisms are competitive in inhibiting those species. QTAIM calculations reveal the existence of critical points in the two conformers. The Diels-Alder intramolecular cyclization of (C-OXY) leads to two new tautomers: trans-cycle-OXY (T-CYCLE-OXY) and cis-cycle-OXY (C-CYCLE-OXY) with a significant improvement in the antioxidant activity. In conclusion, T-OXY and T-CYCLE-OXY are identified as the best antioxidant candidates among those tested.