Electronic structure, DNA-binding, and biological activity correlations in transition metal complexes of a...

A novel tetradentate Schiff base ligand (L), synthesized by the condensation of 2,6-diaminopyridine and 3,5-dichlorosalicylaldehyde, and its Cu(II), Ni(II), Co(II), Zn(II), and VO(IV) complexes were prepared and characterized by elemental analysis, FT-IR, UV-Vis, NMR, ESI-mass, magnetic susceptibility, thermal, and EPR studies. Spectroscopic evidence indicates coordination of the ligand through an N₂O₂ donor set. Based on the available spectroscopic, magnetic, and analytical data, the Cu(II), Ni(II), and Co(II) complexes are proposed to adopt predominantly square-planar geometries, while the Zn(II) and VO(IV) complexes are proposed to possess distorted tetrahedral and square-pyramidal geometries, respectively. DNA-binding interactions with calf thymus DNA were investigated using UV-Vis absorption, viscosity, and electrochemical techniques. The observed hypochromism, minor bathochromic shifts, and viscosity changes suggest a predominantly intercalative binding mode, with intrinsic binding constants (K_b) ranging from 3.59 × 10⁴ to 6.43 × 10⁴ M^-1; the Cu(II) complex exhibited the highest affinity. Electrochemical studies further supported complex-DNA interactions. Density functional theory and molecular electrostatic potential analyses revealed enhanced electronic stabilization, with the Cu(II) and VO(IV) complexes exhibiting the smallest HOMO-LUMO energy gaps. These findings are consistent with their stronger DNA-binding affinity and higher biological activity. Molecular docking provided supportive evidence for favorable biomolecular interactions, particularly for the Cu(II) complex. Metal coordination enhanced the antibacterial, antioxidant, and anti-inflammatory activities compared with the free ligand, with the Cu(II) and VO(IV) complexes showing the most promising overall performance. The results demonstrate correlations between electronic structure, DNA-binding behavior, and biological activity in this class of transition metal complexes.