Design, Synthesis, Physicochemical Characterization, and Prospective Pharmaceutical Applications of Novel Tetra‐Dentate Salen Complexes: DFT and Molecular Docking Insights

ABSTRACTSome novel salen metal chelates of Cu(II), Ni(II), VO(II), and Pd(II) were synthesized using the ligand 2,2'‐((1E,1'E)‐((4, 5‐dimethyl‐1,2‐phenylene) bis(azaneylylidene)) bis(methaneylylidene)) bis(4‐bromophenol). These complexes were extensively characterized through m.p., elemental analysis, TGA, conductivity, and UV–visible spectroscopy. The findings indicated that the ligand functions as a tetradentate ONNO donor, coordinating with Cu(II) and Ni(II) in octahedral geometries, VO(II) in a square pyramidal geometry, and Pd(II) in a square planar geometry. To explore the reactivity and potential biological efficacy of the synthesized metal complexes DFT computations occurred in the gas phase employing the LANL2DZ/B3LYP/6‐311g (d,p) technique. Based on the positive outcomes of our in vitro analyses, we proceeded with molecular docking simulations to provide deeper insights and further validate these remarkable biological activities. The antibacterial properties of the Schiff base ligand and its complexes were evaluated in vitro against gram‐positive and gram‐negative bacteria and various fungal strains. The metal complexes demonstrated significantly greater antimicrobial activity than the free salen imine ligand. The cytotoxic effects of the complexes were also tested against MCF‐7 (breast cancer), HCT‐116 (colon carcinoma), and Hep‐G2 (liver cancer) cell lines. Additionally, antioxidant activity was confirmed using the DPPH free radical scavenging assay. Furthermore, docking insights were applied to confirm the investigated pharmaceutical applications. The growing interest in Schiff base ligands and their metal chelates as promising chemotherapeutic agents has drawn significant attention from medicinal chemists.