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Abstract
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In this study, two new mononuclear Ru(II) polypyridyl complexes, mer-[Ru(pyrrolyl-tpy)(N-N)Cl]Cl (N-N = 2,2′-bipyridine for complex 1 and 1,10-phenanthroline for complex 2), were synthesized and structurally characterized. Kinetic studies of the ligand substitution reactions with biologically relevant nucleophiles (5′-GMP and L-cysteine) revealed that reactivity of complexes is influenced by the electronic nature of the N-N ligands. The data also confirmed the known dependence of the substitution rates on the nature of the entering nucleophile. DNA-binding studies using calf thymus DNA indicated a mixed binding mode partial intercalation and minor groove binding, with complex 2 showing higher affinity. Both complexes also exhibited strong binding to human serum albumin (HSA) without site selectivity, supported by experiments in PBS (pH 7.4) and biocompatible ionic liquids (Bio-ILs), where increased solvent polarity enhanced binding efficiency. Molecular docking corroborated the experimental findings. Complex 2 demonstrated greater cytotoxicity and selectivity toward HeLa cells compared to other cancer and normal cell lines (MRC-5). It induced cell cycle arrest at the G2 phase and showed a concentration-dependent ability to trigger apoptosis, although less pronounced than classical agents like cisplatin. These findings highlight complex 2 as a promising candidate for further investigation, particularly regarding alternative mechanisms of cell death beyond apoptosis.
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