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Abstract
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This study presents the synthesis and comprehensive characterization of four novel Ru(II) polypyridyl complexes with the general formula mer-[Ru(L)(NN)Cl]Cl, where L represents a 4′-substituted terpyridine ligand (2-thienyl or 2-furyl derivatives), and NN denotes either 2,2′-bipyridine (complexes 1 and 3) or 1,10-phenanthroline (complexes 2 and 4). Parallel synthesis of three biocompatible ionic liquids (Bio-ILs) 2-hydroxypropan-1-ammonium lactate (IL1), oxalate (IL2), and citrate (IL3) was achieved with high yields. The Ru(II) complexes were fully characterized by elemental analysis, IR, UV–Vis, 1H/13C NMR, and ESI-MS spectroscopy, confirming their structures and purity. Kinetic studies with guanosine-5′-monophosphate (5′-GMP) and L-cysteine (L-Cys) revealed ligand substitution reactivity in the order 2 > 1 > 4 > 3, influenced by both ligand electronics and nucleophile identity. DNA binding assays using ethidium bromide and Hoechst 33258 showed that all complexes interact with calf thymus DNA via partial intercalation and minor groove binding. Human serum albumin (HSA) binding studies using site-specific probes (eosin Y for site I, ibuprofen for site II) confirmed strong affinity (Kb = 104–105 M−1) for both sites. Notably, Bio-ILs enhanced DNA/HSA binding affinities in the order: PBS < IL1 < IL2 < IL3, attributed to increased solvent polarity. Molecular docking supported the DNA/HSA experimental interaction profiles. Cytotoxicity evaluation via MTT assay on various human cancer cell lines identified complex 3 as the most potent and selective in HeLa cells. However, mechanistic studies indicated that complex 3 did not induce apoptosis or affect cell cycle progression, suggesting a non-classical mode of action.
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