Evaluation of anticancer potential of a binuclear copper(II) complex with a 3-(pyridin-3-yl) coumarin ligand: synthesis, crystal structure, magnetism, DNA interaction and molecular dynamics simulations

A binuclear Cu(II) complex, [Cu2L2(OAc)4]·H2O (Coupy-Cu), with 3-(pyridin-3-yl) coumarin as the ligand, was synthesized by the slow solvent evaporation method. Complex Coupy-Cu was characterized by elemental analysis and infrared spectroscopy, and its crystal structure was determined by X-ray single-crystal diffraction, revealing a distorted octahedral geometry around each copper center. The antiferromagnetically coupled dimeric structure was further confirmed by EPR and VSM, which indicated a diamagnetic singlet ground state (S = 0) with weak paramagnetic susceptibility. Complex Coupy-Cu exhibited favorable cytotoxic activity against a panel of human cancer cell lines (HeLa, A549, MCF-7, and HepG2), with anti-proliferative efficacy against HepG2 cells superior to that of oxaliplatin and induced 43.3% apoptosis at 20 µM in a concentration-dependent manner. It is worth emphasizing that the complex showed significantly lower toxicity toward normal cells compared to cisplatin and oxaliplatin, displaying a safety index 5.2 times that of oxaliplatin and 30.4 times that of cisplatin. Investigations via electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurements, and molecular docking indicated that the complex binds to calf thymus DNA (CT-DNA) primarily through an intercalative mode. This binding was further validated via molecular dynamics simulations, which demonstrated stable complex formation and a calculated binding free energy of −13.74 kcal mol−1, driven predominantly by van der Waals interactions.