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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-[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]

Three dinuclear complexes [Pd2(tpbd)Cl2]Cl2 (PP1), [Pt2(tpbd)Cl2]Cl2 (PP2) and [PdPt(tpbd)Cl2]Cl2 (PP3) (tpbd = N,N,N′,N′-tetrakis(2-pyridylmethyl)benzene-1,4-diamine) have been synthesized and characterized and the protonation constants of their corresponding diaqua analogues have been determined. Also, in water solution, the aqua analogues of these complexes exist as mono-hydroxo, di-hydroxo and dimer μ-hydroxo complexes in the pH between 3.0 and 11.0. Substitution reactions with sulfur- and nitrogen-donor nucleophiles, such as thiourea (Tu), L -methionine (L -Met), glutathione (GSH) and guanosine-5′-monophosphate (5′-GMP), were studied at pH 7.2 by conventional and stopped-flow UV-Vis spectrophotometry and the observed reactivity follows the order: Tu > L -Met > GSH > 5′-GMP. Also, the interactions with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated. Competitive studies with DNA were performed in the presence of ethidium bromide and Hoechst dye 33258 as well. The complexes possess the strong ability to react with CT-DNA exhibiting intercalation and more preferable minor groove binding. Nevertheless, all complexes showed a good binding affinity toward BSA with relatively high binding constants. The nature of the binding forces between complexes and biomolecules has been identified as hydrophobic. Experimental results were compared with the molecular docking results, while the relative stability and thermodynamic properties of dinuclear complexes were compared with their mononuclear units by DFT calculations. Among three tested complexes, PP2 showed the most powerful cytotoxic effect on HTB140 and H460 cancer cell lines after 48 h of treatment and exerted a strong long-term influence on the proliferation potential of both tested cell lines. PP2 induced the inhibition of autophagy, G2/M cell cycle arrest and mitotic catastrophe. [ABSTRACT FROM AUTHOR]

A serie of novel square pyramidal copper(ii) complexes [Cu(L)2H2O] (3a–d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4′-hydroxy-3′-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth microdilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL−1) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 μg mL−1. The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB–DNA complex through intercalation suggesting strong competition with EB [Ksv = (1.4 ± 0.2) and (2.9 ± 0.1) × 104 M−1, respectively]. Ksv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [Ka = (2.9 ± 0.2) × 106 and (2.5 ± 0.2) × 105 M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d– and 3e–BSA complexes. The obtained Ka values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells. [ABSTRACT FROM AUTHOR]