Antioxidation of 2-phenylbenzofuran derivatives: structural-electronic effects and mechanisms

Stilbenoid-type 2-phenylbenzofuran derivatives, which are widely distributed in nature, are now promising antioxidant agents. In the present study, a quantum computational approach principally based on the DFT/B3LYP method with the 6-311++G(d,p) basis set was used to shed light on free radical scavenging for the isolated compounds stemofurans A-K and S-W. On the basis of the findings and from a thermodynamic perspective, the antioxidant activity of all studied compounds in the gaseous phase was mostly controlled by the O-H bond dissociation enthalpy (BDE), consistent with the hydrogen atom transfer (HAT) mechanism. The solvent effect was investigated, and the hydroxyl radicals of these studied compounds possessed the lowest proton affinity (PA) enthalpy and the sequential proton loss electron transfer (SPLET) pathway occurred in water, methanol and acetone. The studied compounds interacted with DPPH radicals, which is kinetic evidence of the involvement of two intermediates and one transition state. From both thermodynamics and kinetics perspectives, it can be proposed that stemofuran U is likely to be a leader compound in antioxidant drug development due to the presence of a 4′-OH moiety. Regarding the structure-bioactivity relationship, methylation can lead to a decrease in BDE. The plausible antioxidative mechanism of 2-phenylbenzofurans based on DFT calculation.