Structure-Activity Relationship of Allicin, Fulvic Acid, and Flavonoid Antioxidants: Unveiling the Role of Quantum Chemical Parameters in Antioxidant Synergy

The research studies allicin compounds that work in conjunction with fulvic acid and various flavonoids to reduce the levels of reactive oxygen species, thereby producing enhanced antioxidant effects.

The antioxidant mechanism involves a complex pathway, and one major step is Hydrogen Atom Transfer (HAT), where the compound donates a hydrogen atom to stabilize the radical. The antioxidant strength depends on many quantum chemical descriptors, which provide quantitative measures of a molecule's electronic structure and properties. Bond Dissociation Enthalpy (BDE) values are a major parameter, and lower BDE values indicate weaker O-H bonds and better hydrogen-donating abilities.

This research used a computational method that combined Density Functional Theory (DFT) with Quantitative Structure-Activity Relationship (QSAR) modeling. We obtained a diverse dataset of flavonoids and performed molecular descriptor calculations. The B3LYP/6-311+G(d,p) DFT method was employed to find Bond Dissociation Enthalpy (ΔBDE) changes for a selected set of compounds. The Random Forest Regressor model was used for ΔBDE data as its target variable to establish a relationship between molecular structures and their synergistic effects. The trained model achieved outstanding predictive accuracy. The number of hydroxyl groups (nOH) and topological polar surface area (TPSA) were used as additional descriptors, as the model demonstrates that H-bond donation ability plays a crucial role in stabilizing radicals.  The EPM identified the most nucleophilic site on fulvic acid combined with allicin as the hydroxyl oxygen attached to a specific ring in the fulvic acid. The EPM analysis detected areas with electron density that are susceptible to electrophilic attack between allicin and fulvic acid.

The research created a dependable ML-QSAR system that enables scientists to design antioxidant combinations through rational methods.