Dinuclear complexes [Pd ₂ (tpbd)Cl ₂ ]Cl ₂ , [Pt ₂ (tpbd)Cl ₂ ]Cl ₂ and [PdPt(tpbd)Cl ₂ ]Cl ₂ (tpbd = N , N , N ′, N ′-tetrakis(2-pyridylmethyl)benzene-1,4-diamine) have been synthesized and the kinetic, interactions with DNA/BSA and cytotoxic activity were studied.

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 (K_b = 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.

The synthesis and structural characterization of a newly synthesized mononuclear rhodium(III) complex, Rhtrz, with a ligand (2,2,6-bis((4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine) and a ligand of 1,2,4-triazole, are presented in this paper. The kinetic interactions of the Rhtrz complex with essential biomolecules such as 5-GMP, L-Met, and GSH were examined. The study of the biological interactions was focused on the binding properties of the Rhtrz complex with CT-DNA and serum albumin. These interactions were investigated using UV-vis spectrophotometry, fluorescence spectroscopy, viscosity measurements, thermal denaturation studies, and electrophoresis. Fluorescence competition experiments with site-markers for BSA were used to locate the binding site of the Rhtrz-complex to the BSA. Molecular docking studies were carried out to obtain detailed binding information of the complex with CT-DNA, BSA, and HSA. Furthermore, the apparent distance between the donor (HSA) and acceptor (Rhtrz) was determined using fluorescence resonance energy transfer (FRET). The thermodynamic properties and relative stabilities of the Rhtrz complex were examined, constructing the two model equation by DFT calculations (B3LYP(CPCM)/LANL2DZp). In vitro cytotoxicity and redox status on the human epithelial colorectal cancer cell line (HCT-116) and healthy human fibroblast cell line (MRC-5) were also investigated.

Two gold(III) complexes, square-planar [Au(DPP)Cl₂]⁺(1) and distorted square-pyramidal [Au(DMP)Cl₃] (2) (where DMP = 2,9-dimethyl-1,10-phenanthroline and DPP = 4,7-diphenyl-1,10-phenanthroline), were studied by different experimental methods. Their stability in water and in buffer solution (25 mM Hepes, 30 mM NaCl, pH = 7.2) was investigated by UV-Vis spectroscopy while their redox stability is confirmed by CV. Substitution reactions between complexes 1 and 2, and biologically relevant ligands, such as thiourea (Tu), guanosine-5′-monophosphate (5′-GMP), glutathione (GSH) and L-methionine (L-Met), were studied by a stopped-flow technique, under the pseudo-first order conditions as a function of ligand concentration and temperature. According to the values of the activation parameters, all studied reactions followed an associative substitution mechanism. DNA binding studies of complexes 1 and 2 were performed by UV-Vis and fluorescence spectroscopy and viscosity measurements, as well as interactions with bovine serum albumin (BSA). Density functional theory (DFT) was implemented in order to analyse the wave function of the optimized structures to get better insight into the binding interactions between the inert ligands and gold(III) center. The experimental results of binding studies with DNA and BSA were simulated and compared by performing a molecular docking study. All results demonstrate the strong connection between the reactivity of the complexes toward biologically important targets and their structural and electronic characteristics. The cytotoxic activity of complexes 1 and 2 against different cell lines (MDA-MB-231, HCT-116, and HaCaT) was evaluated 24 and 72 h after treatments. The results indicate reduced viability of cell lines in a time- and dose-dependent manner.

Within this paper is presented the synthesis and structural characterization of three newly synthesized osmium(II) complexes Os1–3, with the chemical formula [Os^IILCl₂H₂O], [L = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (for Os1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (for Os2) or 2,2′:6′,2′′-terpyridine (for Os3)]. Single crystal X-ray analysis of a DMSO adduct of complex Os1 was performed. Kinetics of substitution reactions of examined Os1–3 complexes with biomolecules 5-GMP, L-Met, and GSH were followed in the presence and absence of different biocompatible ionic liquids. Binding properties of the examined complexes to biologically important molecules, CT-DNA and HSA, were investigated using UV-Vis spectrophotometry, fluorescence spectroscopy, and gel electrophoresis. Interactions with CT-DNA were performed both in the absence and presence of biocompatible ionic liquids. To locate the binding site and possible binding mode of the examined complexes to CT-DNA and HSA, fluorescence competition experiments with site-markers were performed. To better understand these interactions and obtain detailed binding information of the examined complexes with CT-DNA, and HSA, molecular docking studies and fluorescence resonance energy transfer (FRET) were performed. In vitro cytotoxicity and redox status experiments on three cancer cell lines and on one healthy cell line were performed to elucidate the possible molecular mechanisms of investigated Os1–3 complexes.