Synthesis, antioxidant activity, and density functional theory study of some novel 4-[(benzo[d]thiazol-2-ylimino)methyl]phenol derivatives: a comparative approach for the explanation of their radical scavenging activities

BACKGROUND AND PURPOSE: Radicals produced by Fenton and Haber-Weiss reactions play detrimental roles in our body. Some oxidized proteins as toxic configurations are identified in amyloid-β deposits. These deposits mostly occur in conditions, such as Alzheimer’s disease. Here, we report the synthesis, evaluation of the antioxidant activity, and implementation of density functional theory (DFT) calculations of some4- [(benzo[d]thiazol-2-ylimino) methyl]phenol derivatives. The aim of this study was to provide a comparative theoretical-experimental approach to explain the antioxidant activities of the compounds. EXPERIMENTAL APPROACH: Compounds were synthesized by the reaction between para hydroxybenzaldehyde and aminobenzothiazole derivatives. The scavenging activity of the compounds was evaluated. Various electronic and energetic descriptors such as high occupied molecular orbital and low unoccupied molecular orbital energy gaps, bonding dissociation enthalpy of OH bond, ionization potential, electron affinity, hardness, softness, and spin density of the radical and neutral species were calculated. DFT calculations with B3LYP hybrid functional and 6-311++ G** basis set in the polarizable continuum model were utilized to obtain these descriptors. FINDINGS/RESULTS: Ascorbic acid showed the best DPPH scavenging activity. However, 4d and 4c showed promising antioxidant activity. The values of EHOMO for 4c and 4d were closer to zero, thus, they showed the best scavenging activities. The computational results were in accordance with the experimental ones. The energetic descriptors indicated that the sequential proton loss-electron transfer mechanism is preferred over other mechanisms. CONCLUSION AND IMPLICATION: Antioxidant activity of 4-[(Benzo[d]thiazol-2-ylimino) methyl]phenol derivatives confirmed by experimental and theoretical documents proves them as novel antioxidants against amyloid-β based disease.