A detailed DFT-based study of the free radical scavenging activity and mechanism of daphnetin in physiological environments

Abstract

Daphnetin, a biologically active coumarin derivative found in plants of the genus Daphne, is a potent antioxidant phenolic compound. The present work describes the mechanisms and kinetics of the HO, NO, HOO, and NO₂ scavenging activities of daphnetin in physiological environments using quantum chemistry calculations. The main antiradical mechanisms have been studied: formal hydrogen transfer (FHT), sequential electron transfer proton transfer (SETPT), sequential proton loss electron transfer (SPLET), and radical adduct formation (RAF). Besides its good HO scavenging activity in physiological environments, daphnetin is expected to exhibit good HOO and NO₂ scavenging activities in water with k_overall = 1.51 × 10⁷ and 4.79 × 10⁸ M^-1s^-1, respectively. The FHT mechanism decides the HO scavenging activity in aqueous solution, as well as HO, HOO, and NO₂ scavenging activities in lipid media, while SPLET is the primary mechanism in water for HOO and NO₂ scavenging activities. The theoretical predictions were found to be in good agreement with the available experimental data, which supports the reliability of the calculations.

Keywords: Antioxidant mechanisms; Antiradical activity; DFT calculations; Daphnetin; Kinetic study.