Theoretical Study of Antioxidant and Prooxidant Potency of Protocatechuic Aldehyde

In this study, the antioxidant and prooxidant potency of protocatechuic aldehyde (PCA) was evaluated using density functional theory (DFT). The potency of direct scavenging of hydroperoxyl (HOO^•) and lipid peroxyl radicals (modeled by vinyl peroxyl, H₂C=CHOO^•) involved in lipid peroxidation was estimated. The repair of oxidative damage in biomolecules (lipids, proteins and nucleic acids) and the prooxidant ability of PCA phenoxyl radicals were considered. The repairing potency of PCA was investigated for damaged tryptophan, cysteine, leucine, DNA base guanine and linolenic acid. The thermodynamics and kinetics of the single electron transfer (SET) and formal hydrogen atom transfer (fHAT) mechanisms underlying the studied processes were investigated under physiological conditions in aqueous and lipid environments using the SMD/M06-2X/6-311++G(d,p) level of theory. Sequestration of catalytic Fe²⁺ and Fe³⁺ ions by PCA, which prevents HO^• production via Fenton-like reactions, was modeled. Molecular docking was used to study the inhibitory capability of PCA against xanthine oxidase (XO), one of the enzymes producing reactive oxygen species. The attained results show that PCA has the capability to scavenge lipid peroxyl radicals, repair damaged tryptophan, leucine and guanine, chelate catalytic iron ions and inhibit XO. Thus, PCA could be considered a possible multifunctional antioxidant.