Influence of Steric and Electronic Effects in Structure‐Activity Relationships of Schiff Base Ligands: Green Synthesis, Characterization, DFT/TD‐DFT Calculations, Molecular Docking and Biological Studies

Abstract

AbstractThree novel Schiff base ligands derived from 2‐(benzylthio) aniline and substituted benzaldehydes, i. e., 3,5‐di‐tert‐butyl‐2‐hydroxybenzaldehyde, 3,5‐dibromo‐2‐hydroxybenzaldehyde, and 2‐hydroxy‐4‐methylbenzaldehyde, respectively were synthesized in almost quantitative yields employing environmentally friendly techniques such as microwave‐assisted reaction and green solvents. To explicate all the structural and characteristic attributes of synthesized ligands, a combined experimental and theoretical investigation was done. The experimental characterization was conducted by applying elemental analysis, FT‐IR, 1H‐NMR, 13C‐NMR, ESI‐MS, and UV‐Vis spectroscopy. The theoretical calculations of optimized energy, geometrical parameters, electronic spectra, natural atomic charges, 3D plots of MEP, and vibrational wavenumbers were computed and elucidated using DFT and TD‐DFT methods. The calculations were performed by employing B3LYP/6‐311+G(d,p) level. In‐vitro DNA binding affinity of the ligands was studied by UV‐Vis spectroscopy, fluorescence spectroscopy, and molecular docking. The binding constant values obtained for ligands A−C were 3.26×103 M−1, 1.43×104 M−1, and 4.95×103 M−1, respectively. Moreover, the bioactivities of these ligands were probed for their in‐vitro antioxidant and anti‐inflammatory activities. Interestingly, in both the activity ligand C was found to be more biologically potent. A molecular docking investigation was also performed to acquire more information about the binding mode and energy.