A Computational Exploration on the Antioxidant Activity of Vanillic Acid and Its Derivatives

Vanillic acid's ability to effectively quench-free radicals has sparked widespread interest in its antioxidant potential. The title molecule's structure was optimized using the Gaussian 16 program with the B3LYP/6-31+G(d,p) basis set. Natural bond orbital (NBO) calculations reveal that the O-(2)-H-(19) bond in vanillic acid is labile, facilitating the generation of a free radical. The high-bond dissociation energy (BDE) of vanillic acid raises concerns about its efficacy as an antioxidant, particularly when compared to gallic acid (GA) and butylated hydroxy toluene (BHT). Introduction of electron-donating groups (EDGs) at the 10th position significantly enhanced the antioxidant activity of vanillic acid. Vanillic acid and its derivatives show enhanced safety profiles, outperforming BHT in toxicological studies. This paper presents a systematic investigation of vanillic acid and its derivatives, focusing on structural analysis, solvent effects, antioxidant mechanism and toxicological evaluation.