Computational insight into the Fe(II) chelation of Hibiscetin for the enhanced antioxidant activity

Hibiscetin, a major bioactive ingredient of Hibiscus sabdariffa, exhibits numerous pharmacological actions and five metal-chelating sites. Since flavonoids play a vital role in scavenging or reducing the toxicity of redox-active metal ions, the chelation of Fe²⁺ cation by the flavonoid Hibiscetin was examined using the DFT method carried out at the M06-2X/6-311+G(d, p)/LANL2DZ level of theory in the aqueous phase. All the complexed species derived from neutral and deprotonated ligand forms were considered. The results show that the oxygen atoms of the di-deprotonated catechol moiety at the C-7 and C-8 positions of Hibiscetin interact best with the Fe²⁺ ion among the possible chelation sites on Hibiscetin. The stability of the most stable complex, HIB-[7-8] -Fe²⁺, was validated by Frontier molecular orbital, Natural bond orbital, and natural population reports. The topological analysis indicated the electrostatic interaction between the oxygen atoms of Hibiscetin and the metal ion in the complex. The investigation of the radical scavenging capabilities in gas, water, and benzene media proved the superior antioxidant activity of the most stable complex of Hibiscetin and Fe²⁺ ion when compared to parent flavonoid. The hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET) mechanisms were studied, and the HAT mechanism was found to be the most effective radical scavenging mechanism in the gas and non-polar solvent and the SPLET mechanism in the polar solvent. The best site for radical attack is identified to be 4'-OH.