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This paper presents the synthesis and structural characterization of a series of new ruthenium(II) complexes 1-7, with the general formula mer -[RuL 3 ( N - N )Cl]Cl, where L is 2,2':6',2''-terpyridine (tpy) or 4'-(4-chlorophenyl)-2,2':6',2''-terpyridine (Cl-Ph-tpy) and N - N is o -benzoquinonediimine ( o -bqdi), 2,3-naphthoquinonediimine (nqdi), 4,4'-dimethyl-2,2'-bipyridine (dmbpy) or 2,2'-bipyridine-4,4'-dicarboxylic acid (dcbpy). The kinetic results showed that the ligand substitution reactions of new Ru(II)-polypyridyl complexes with biomolecules were affected by different substituents and the aromaticity of meridional tridentate and bidentate spectator ligands as well as by the nature of the entering nucleophile. The reactivity of the complexes increases in the order: dmbpy < dcbipy < nqdi < o -bqdi. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data. Furthermore, combining ethidium bromide (EB) and Hoechst 33258 (2-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl)benzimidazo-2-yl]-benzimidazole) fluorescence assay results implied that 1-7 might interact with calf thymus DNA through partial intercalation and/or minor groove binding. The human serum albumin (HAS)-fluorescence binding studies involving the site markers, eosin Y, as a marker for site I of subdomain IIA, and ibuprofen, as a marker for site II of subdomain IIIA, showed that Ru(II) compounds bind to both sites with moderately strong affinity ( K b = 10 4 -10 6 M -1 ). Moreover, these DNA/HSA experimental results were confirmed by molecular docking. Complexes 2, 5 and 6 exerted good to strong and highly selective cytotoxic activity against breast adenocarcinoma (MDA-MB 231), colorectal carcinoma (HCT116) and cervix adenocarcinoma (HeLa). Depending on their structure and cell line, the complexes acted differently in terms of their influence on autophagy, the cell cycle and the engaged apoptotic pathway.

This paper presents the synthesis and structural characterization of a series of new ruthenium(II) complexes 1–7, with the general formula mer-[RuL3(N–N)Cl]Cl, where L is 2,2′:6′,2′′-terpyridine (tpy) or 4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine (Cl-Ph-tpy) and N–N is o-benzoquinonediimine (o-bqdi), 2,3-naphthoquinonediimine (nqdi), 4,4′-dimethyl-2,2′-bipyridine (dmbpy) or 2,2′-bipyridine-4,4′-dicarboxylic acid (dcbpy). The kinetic results showed that the ligand substitution reactions of new Ru(II)-polypyridyl complexes with biomolecules were affected by different substituents and the aromaticity of meridional tridentate and bidentate spectator ligands as well as by the nature of the entering nucleophile. The reactivity of the complexes increases in the order: dmbpy < dcbipy < nqdi < o-bqdi. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data. Furthermore, combining ethidium bromide (EB) and Hoechst 33258 (2-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl)benzimidazo-2-yl]-benzimidazole) fluorescence assay results implied that 1–7 might interact with calf thymus DNA through partial intercalation and/or minor groove binding. The human serum albumin (HAS)-fluorescence binding studies involving the site markers, eosin Y, as a marker for site I of subdomain IIA, and ibuprofen, as a marker for site II of subdomain IIIA, showed that Ru(II) compounds bind to both sites with moderately strong affinity (Kb = 104–106 M−1). Moreover, these DNA/HSA experimental results were confirmed by molecular docking. Complexes 2, 5 and 6 exerted good to strong and highly selective cytotoxic activity against breast adenocarcinoma (MDA-MB 231), colorectal carcinoma (HCT116) and cervix adenocarcinoma (HeLa). Depending on their structure and cell line, the complexes acted differently in terms of their influence on autophagy, the cell cycle and the engaged apoptotic pathway. [ABSTRACT FROM AUTHOR]

Two new neutral ruthenium(II) complexes [Ru(η6‐p‐cymene)Cl2(1)] (3) and [Ru(η6‐p‐cymene)Cl2(2)] (4) (1=5‐(phenylamino)‐3‐pyrrolidin‐1‐ylisothiazole‐4‐carbonitrile; 2=3‐morpholin‐4‐yl‐5‐(phenylamino)isothiazole‐4‐carbonitrile) have been synthesized and characterized using elemental analysis, IR, UV‐Vis and NMR spectroscopy. The crystal structure was confirmed for complex 3 and both ligands. Examination of the interactions of ligands and complexes with CT‐DNA (Calf Thymus DNA), as well as with HSA (Human Serum Albumin) revealed that ligands and complexes could interact with CT‐DNA through intercalation and could bind strongly with HSA. Docking experiments toward DNA dodecamer indicate excellent accordance with experimental ΔG values. The cytotoxic activity of ligands and complexes was evaluated by MTT assay against HCT116 and HeLa tumoral cells. The complexes 3 and 4 showed good activity and selectivity on HCT116 cells. Neither of the tested compounds shows cytotoxic activity against a healthy MRC‐5 cell line. Flow cytometry analysis showed the apoptotic death of the HCT116 cells with a cell cycle arrest in the S‐phase. [ABSTRACT FROM AUTHOR]