Theoretical Study for Exploring the Diglycoside Substituent Effect on the Antioxidative Capability of Isorhamnetin Extracted from Anoectochilus roxburghii

[Image: see text] Radical-scavenging activity of isorhamnetin (1) and its diglycosides, named isorhamnetin-3,5’-O-β-D-diglucoside (2) and isorhamnetin-3,7-O-β-D-diglucoside (3) extracted from Anoectochilus roxburghii, has been studied through three main antioxidant pathways: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer, and sequential proton loss electron transfer (SPLET). All thermodynamic parameters related to these radical-scavenging mechanisms were computed at the B3LYP/6-311G(d,p) level of theory both in the gas phase and in solution. The results suggest that HAT is the predominant mechanism in the gas phase, while SPLET is supported in an aqueous environment. In addition, the stability of radicals has also been explored by electron spin density and intramolecular hydrogen bonding. The potential energy profiles and kinetic calculations for the reactions between the selected compounds and the CH(3)OO(•) radical were calculated at 298.15 K. Among all investigated, compound 2 has the highest antioxidant activity with the lowest Gibbs free energy (−4.05 kcal/mol) and the highest hydrogen atom transfer rate constant (3.61 × 10(5) M(–1) s(–1)). Substitution of the OH and OMe groups by two glucoses at the 3 and 5′ sites of isorhamnetin has a significant impact on its antioxidant activity.