Design, Optimized Synthesis, and Coordination Behavior of Quinolinic Benzimidazoles with Cu(II) and Ni(II): Reactivity Toward ROS, Computational Studies, and Biological Profiling

Benzimidazole is a well‐known pharmacophore present in 47 FDA‐approved drugs and ≈100 experimental compounds. It shows promise for other applications, including antibacterial, antifungal, antiviral, and anticancer therapies. Many derivatives modulate oxidative stress by influencing reactive oxygen species (ROS), selectively inducing cancer cell death. Additionally, structural modificationsenhance antitumor activity and facilitate conjugation with metal centers. In this study, it is focused on the hybrid ligand 2‐(1H‐benzo[d]imidazol‐2‐yl)quinolin‐8‐ol ( L ) and its Cu(II) and Ni(II) complexes ( 1 and 2 ) as potential anticancer agents. These coordination systems are characterized, and their binding stability is assessed via UVvisible titrations and density functional theory (DFT) analysis, revealing that complex 2 is more stable than complex 1 . It is then investigated how the ligand and the complexes can interact with ROS, with a view to a ROS‐targeting cytotoxicity. These studies, supported by DFT, indicated that L and complex 1 are generally more interactive than complex 2 . When tested on various cancer cell lines, it is found that L and complex 1 demonstrated modest to good efficacy. These results suggest that L is the primary active species, complex 1 acts as a prodrug, whereas the strong interaction with Ni(II) in 2 hinders the ligand's potential.