The antioxidant activity of bergaptol (4-hydroxyfuro[3,2-g]chromen-7-one, BER) and xanthotoxol (9-hydroxyfuro[3,2-g]chromen-7-one, XAN) was investigated in water and benzene, as solvents. For this purpose, the density functional theory (DFT) was used. The free radical scavenging potency of investigated compounds towards different reactive oxygen species (ROS) was performed. Antioxidative mechanism of investigated compounds – hydrogen atom transfer (HAT), single-electron transfer–proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) were examined using M06-2X/6-311++G(d,p) theoretical model. The important thermodynamic parameters (BDE, IP, PDE, PA, ETE) and Gibbs free energies of reactions, were used to determine the most probable antioxidant mechanism of action. The obtained thermodynamic parameters suggested that Hydrogen Atom Transfer (HAT) is the most probable reaction pathway in benzene, while Sequential Proton Loss Electron Transfer (SPLET) was favorized in water. The obtained results indicate that the favorable mechanism of antiradical activity depends on the polarity of medium and the nature of free radical species. By comparing the antioxidant activity of investigated compounds, it can be concluded that bergaptol exhibits better antioxidant properties. Molecular docking study of neutral and anionic species of investigated compounds was performed according to Estrogen receptor alpha (ERα). In both cases, bergaptol showed better inhibitory potency. All the anionic species showed a higher inhibition constant, indicating lower inhibition potency than corresponding parent molecules.
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