Antioxidant Activity of Rooperol Investigated through Cu (I and II) Chelation Ability and the Hydrogen Transfer Mechanism: A DFT Study

Rooperol is a norlignan derivative with numerous biological activities including immunomodulatory, antitumor, anticonvulsant, antibacterial, and antioxidant activities. Its antioxidant activity has been studied by means of experimental techniques, which have shown that it has the ability to scavenge radical species, inhibit lipid peroxidation, and reduce transition metal ions. However, its ability to scavenge radical species and chelate transition metal ions has not been previously studied by means of quantum chemical methods. In this study, density functional theory (DFT) is utilized to investigate the conformational preferences of rooperol, the ability of rooperol to scavenge radical species, and the rooperol···Cu interaction mechanism, which might assist in understanding the antioxidant and prooxidant activities of rooperol. The study was performed <i>in vacuo</i> and in selected solvents. The results suggest that lowest-energy conformers of neutral rooperol are stabilized by two intramolecular hydrogen bonds, while the radical species of rooperol are stabilized by both intramolecular hydrogen bonds and spin delocalization of the unpaired electron. The results in different solvents show that the stability of the conformers of rooperol increases with the increase in the solvent polarity, while the stability of radical species decreases with increase in solvent polarity. The stability of the rooperol···Cu complexes depends on the site on which the Cu ion binds, while the binding strength depends on both the nature of the cation and the nature of the binding site. The inclusion of solvent effects using the polarizable continuum model shows that the rooperol···Cu interaction energies are highly overestimated <i>in vacuo</i>. Finally, the results suggest that the antioxidant activity shown by rooperol corresponds to its interaction with closed-shell transition metal ions, while its prooxidant activity is a result of its interaction with open-shell transition metal ions