Theoretical investigation and molecular docking approach on the antioxidant activity of Schiff bases and their tautomers

Abstract

A theoretical study of the antioxidant behavior of N[Formula: see text]-(2-hydroxy-3-methoxy-benzylidene)-4-tert-buty-lenzohydrazide (1), N[Formula: see text]-(5-bromo-2-hydroxy-benzylidene)-4-tert-butyl benzohydrazide (2) and N[Formula: see text]-(2-hydroxy-3-methoxybenzylidene)-4-methyl-benzene-sulfonohydrazide (3) and their tautomers 1 [Formula: see text] –3 [Formula: see text] have been carried out at B3LYP/6-31[Formula: see text]G(2d,2p). The numerical values of descriptors, namely, bond dissociation enthalpy, proton affinity (PA), electron transfer enthalpy (ETE), ionization potential, and proton dissociation enthalpy (PDE) have been calculated in gas phase and media solution (EtOH, DMSO and water). The obtained results show that the hydrogen atom transfer (HAT) mechanism is more favored thermodynamically in gas phase, whereas the sequential proton loss electron transfer (SPLET) mechanism is more preferred in solvents. Moreover, the couple (3,3[Formula: see text]) is found to be the most potent antioxidant as expected experimentally. Furthermore, the BDE values of compound 3 [Formula: see text] is much lower than that of ascorbic acid (AA), indicating that the tautomerization of compounds 1–3 has great influence on the antioxidant activity of these compounds. The antioxidant power of compounds (3.3[Formula: see text]) was also rationalized by the calculation of the atomic spin density. In addition, the molecular docking study of compounds 1–3 and 1[Formula: see text] –3[Formula: see text] on xanthine oxidase (XO) as the protein target revealed important interactions between active compounds and amino acids. Moreover, compound 3 is predicted to be a potential inhibitor with higher activity.