Theoretical evaluation of the antiradical activity of 1-Hydroxy-anhydrolycorin-7-one and anhydrolycorin-7-one from Lycoris aurea.

CONTEXT: The antiradical activity of 1-hydroxy-anhydrolycorin-7-one (HAlc) and anhydrolycorin-7-one (Alc), two alkaloids isolated from Lycoris aurea, was theoretically investigated toward HOO• radical scavenging in aqueous and lipid-like environments. Thermodynamic analysis showed that HAlc is more favorable than Alc as a radical scavenger, mainly due to the additional hydroxyl group, which enhances both hydrogen atom donation and deprotonation ability. Among the investigated sites, the 2-OH group of HAlc displayed the lowest BDE and PA values and the most negative Gibbs free energy changes, indicating its key role in radical quenching. In pentyl ethanoate, HAlc scavenges HOO• predominantly through the fHAT mechanism at the 2-OH position, with an overall rate constant of 4.29 × 106 M⁻1 s⁻1, approximately two orders of magnitude higher than that of Alc. In water, acid-base speciation strongly affects the scavenging mechanism. Although the neutral forms are dominant at physiological pH, the minor monoanionic species govern the overall kinetics through a highly efficient SET pathway. HAlc exhibited an overall aqueous rate constant of 3.04 × 108 M⁻1 s⁻1, about 16 times higher than Alc and higher than common antioxidant references such as Trolox and ascorbic acid. These results identify HAlc as a promising natural antiradical agent, especially under physiological aqueous conditions. METHODS: All calculations were performed using Gaussian 09. The most stable conformers were optimized by density functional theory at the M06-2X/6-311++G(d,p) level. Solvent effects were described using the SMD model with water and pentyl ethanoate. The fHAT, SETPT, and SPLET mechanisms were evaluated using BDE, IP, PA, and reaction Gibbs free energies. Kinetic calculations were carried out following the QM-ORSA protocol. Transition states for fHAT reactions were confirmed by single imaginary frequencies associated with hydrogen transfer, tunneling corrections were included, and SET activation barriers were estimated using Marcus theory. Apparent and overall rate constants were calculated by considering acid-base molar fractions at pH 7.4.