Comprehensive Study on Synthesis, Quantum Chemical Calculations, Molecular Modeling Studies, and Cytotoxic Activities of Metal(II) Schiff Base Complexes

Abstract

In this study, mononuclear Ni(II), Cu(II), Zn(II), and Pd(II) complexes of a diimine molecule (H₂L) were synthesized, and their structures were elucidated by NMR, FT-IR, UV–Vis, ICP-OES, molar conductivity, magnetic susceptibility, and elemental analysis techniques. Stoichiometric and spectroscopic data revealed that the complexes have a metal:ligand ratio of 1:1 and the Schiff base coordinates with the metal(II) ion via nitrogen atoms of two imine groups and oxygen anions of two phenolate moieties and have a square planar geometry. The cytotoxic activity properties of the ligand and its metal complexes were screened in two distinct cancer cell lines: lung (A549) and colon (DLD-1). The optimized molecular geometries, molecular electrostatic potential diagrams, total density of states plots, and frontier molecular orbitals of the H₂L ligand and all metal(II) complexes at the ground level were calculated using density functional theory. The LANL2DZ basis set containing the effective core potentials for transition metals was used for quantum chemical calculations. The calculations supported the square planar geometry of the metal(II) ions in the complexes. The potential of all molecules to inhibit the MLK4 kinase domain (PDB ID: 4UYA) involved in cancer progression was examined by molecular docking study and the best inhibition activity belonged to the H₂L molecule with a binding energy of −10.8 kcal/mol. The stability of the H₂L–4UYA complex in physiological media was also confirmed by molecular dynamics simulation for 100 ns.