Synthesis and Theoretical Evaluation of New Copper(II) Complexes Associated with a Crystalline Schiff Base: DNA/BSA Protein Interaction, Radical Scavenging and Cytotoxicity

Abstract A crystalline dihydroxy substituted Schiff base ligand [ LH ] was involved in the synthesis of three copper(II) complexes viz [Cu(LH) 2 ] ( Cu1 ), [Cu(LH)(bpy)] ( Cu2 ) and [Cu(LH)(phen)] ( Cu3 ) (bpy=2,2’‐bipyridine and phen=1,10‐phenanthroline). FTIR, ESI‐MS, elemental analysis, ESR studies and NMR techniques were employed to characterize all the newly synthesized compounds. Monoclinic structure with space group P2 1 /n of ligand ( LH) was confirmed by single crystal XRD analysis. The molecular structure of ligand and complexes were optimized using density functional theory (DFT) at B3LYP/LanL2DZ levels in the gas phase. According to DFT investigations Cu1 exhibits tetragonally distorted octahedral geometry around Cu(II) while Cu2 and Cu3 appeared in penta‐coordination as distorted trigonal bipyramidal geometry. UV‐Vis, fluorescence and viscosity titrations were used to examine the metal complex interactions with CT‐DNA and BSA protein. The binding results suggest that the complexes bind to DNA via groove binding mode. Molecular docking was performed to analyse the binding interaction of complexes with BSA and DNA. Antioxidant investigation indicates that the Cu1 possesses remarkable ability to scavenge radicals against DPPH due to the lowest IC 50 value 211.20 μg/mL. In‐vitro cytotoxicity was assessed against MCF‐7 breast cancer cells where Cu1 was found to have superiority in cytotoxicity with IC 50 value 52.35 μm over other analogues. Acridine orange/ethidium bromide staining analysis of Cu1 were used to determine apoptosis as the cause of cell death.