Binuclear [Cu(bipyridine)(NO3)(OH)]2 complex: structural characterization, DFT calculations, molecular docking, and cytotoxicity against breast adenocarcinoma cells

Copper(II) complexes with aromatic N-heterocyclic ligands have attracted considerable attention as potential anticancer agents due to their capacity to interact with DNA and inhibit tumor cell proliferation. Despite the structural characterization of the binuclear [Cu(Bipyridine)(NO 3 )(OH)] 2 complex reported nearly three decades ago, its physicochemical and biological landscape remained largely unexplored. In the present work, a comprehensive characterization of this complex is reported, encompassing experimental and computational approaches. The complex was synthesized by slow solvent evaporation and confirmed by powder X-ray diffraction (PXRD) with Rietveld refinement, which established a triclinic structure (space group , Z = 1) with lattice parameters in good agreement with literature values (ΔV = 0.44%). Ultraviolet-visible spectroscopy revealed a d-d transition at 641 nm, from which a crystal field splitting parameter of 10Dq ≈ 15,601 cm –1 was estimated, confirming the stronger ligand field of 2,2-bipyridine relative to water. Density functional theory (DFT) calculations using the PBE1PBE functional in vacuum, water, and methanol revealed the triplet state as the most stable configuration and demonstrated a solvation-dependent increase in the HOMO-LUMO gap (3.40 eV in vacuum; 4.65 eV in water), reflecting enhanced electronic stability under physiological conditions. High electrophilicity values ( ϖ = 5.05-5.51 eV) support the potential for interactions with biological nucleophiles. Hirshfeld surface analysis quantified the dominant intermolecular interactions in the crystal lattice, with H···O/O···H contacts accounting for 41.1% of the surface. A group-theory-based normal mode analysis provided suitable assignment of the observed modes, with strong agreement between experimental and DFT-calculated spectra. Thermal analysis demonstrated stability up to 473 K, confirmed by variable-temperature PXRD up to 620 K. Molecular docking revealed affinity for DNA ( K i = 6.27 μM, PDB: 1BNA) and the breast cancer-associated 3α-hydroxysteroid dehydrogenase type 3 enzyme ( K i = 36.69 μM, PDB: 4XO6). In silico pharmacokinetics profiling indicated limited oral bioavailability due to high topological polar surface area (TPSA = 169.18 Å 2 ), though favorable water solubility (Log S = 0.31) and absence of CYP450 inhibition suggest low hepatotoxicity risk. Cytotoxicity assays yielded IC 50 values of 39.73 μM and 14.46 μM against MCF-7 breast adenocarcinoma and GM07492A healthy fibroblast cell lines, respectively, with a selectivity index of 0.36. These results establish [Cu(Bipyridine)(NO 3 )(OH)] 2 as a biologically relevant binuclear Cu(II) candidate whose tumor selectivity may be improved through targeted nanoencapsulation strategies.