Synthesis, characterization, electronic properties, and cytotoxic activities on cancer cells line of novel Cu(II) complexes with benzimidazole-Schiff base tridentate ligand

•Cu(II) complexes with benzimidazole Schiff base were synthesized and characterized.•DFT was employed to calculate the optimized structures.•The spectroscopic and electrochemical properties of the complexes were assessed.•The cytotoxicity was evaluated against MCF-7 and SW620 human tumor cells.•DNA binding study indicated an intercalative binding of the complexes with CT-DNA. Three Cu(II) complexes were synthesized using a benzimidazole-Schiff base ligand (L), aiming to develop novel copper complexes with potent cytotoxic effects against breast and colorectal cancer cells. This study investigates the influence of the counter anion ClO₄⁻ in complex 1 ([Cu(L)(H₂O)]ClO₄) and the co-ligands (aqua in 1 [Cu(L)(H₂O)]ClO₄; acetate in 2 [Cu(L)(OAc)]; and nitrate in 3 [Cu(L)(NO₃)]) on the structural stability and anticancer activity of the complexes. We present both experimental and theoretical analyses of these complexes. Complex 1 ([Cu(L)(H₂O)]ClO₄ was characterized by X-ray crystallography, revealing a single molecular structure with a copper center coordinated to the monoanionic tridentate benzimidazole‐imine ligand and one water molecule, resulting in a slightly distorted square planar geometry. All complexes were characterized by infrared (IR) spectroscopy, UV-visible (UV-vis) spectroscopy, and high-resolution mass spectrometry (HRMS). Elemental analysis was conducted to confirm the purity of the complexes. Their redox properties were examined by cyclic voltammetry. Computational studies were performed using ORCA 5.0 software. The optimized molecular structures, HOMO-LUMO analyses, and chemical reactivity descriptors were calculated at the B3LYP/def2-TZVP/def2-SVP theoretical level and are discussed herein. The short interatomic interactions in the crystal structure of 1 were evaluated by mapping the Hirshfeld surface process using pseudo-mirrored 2D fingerprint plots. In vitro cytotoxicity studies of L and Cu(II) complexes (1–3) using the MTT assay showed moderate cytotoxicity for complexes 2 and 3 against MCF-7 and SW620 cell lines, though they exhibited non-selective effects on MRC-5 cells. Interestingly, L and complex 1 demonstrated cytotoxicity against SW620 cells, but not against MRC-5, with IC₅₀ values of 56.7 µM and 54.8 µM, respectively. DNA binding study using UV-vis spectroscopy assays indicated an intercalative binding of the complexes with CT-DNA. ADME/Tox predictions suggested that all three complexes adhered to Lipinski's Rule of Five (Ro5). [Di