Hydroxyl Radical Scavenging by Aucubin: A Mechanistic Study

This study investigates the antioxidant properties of aucubin (AU), an iridoid compound, focusing on its ability to scavenge hydroxyl radicals (^•OH) through its hydroxyl functional groups. Gaussian software was employed to model and validate the underlying antioxidant reaction mechanisms. Three primary pathways were examined: hydrogen atom transfer (HAT), sequential electron transfer-proton transfer (SET-PT), and sequential proton loss–electron transfer (SPLET). All calculations were performed using the M06-2X functional within density functional theory (DFT) at the def2-TZVP level, incorporating Grimme’s D3 dispersion correction and the implicit solvation model based on solute electron density (SMD) for water. Various thermodynamic parameters were determined to analyze and compare the antioxidant reactions, including the O-H bond dissociation energy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), electron transfer enthalpy (ETE), and proton affinity (PA) of the hydroxy groups. The results indicated that the HAT mechanism is the dominant pathway in the scavenging of ^•OH radicals by AU. The key active sites were identified as the 6-OH group in the aglycone structure and the 6′-OH group in the sugar moiety. Moreover, the polar aqueous environment promoted O-H bond homolysis through hydrogen bonding interactions, thereby enhancing the antioxidant activity, and the polar aqueous environment promoted O-H bond homolysis to enhance the antioxidant activity.