Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol

The platinum (II)complexes, cis-[PtCl2(CH3SCH2CH2SCH3)] (Pt1), cis-[PtCl2(dmso)2] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl2(NH3)2] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis

Effects of micelles on the complex formation of [PtCl(dien)](+) with biologically relevant ligands

Substitution reactions of [PtCl(dien)](+) (dien = diethylenetriamine) with some biologically relevant ligands, such as L-methionine ((L)-Met), glutathione (GSH), and guanosine 5-nionophosphate (5-GMP), were studied in aqueous 0.10, 0.05, and 0.01 M NaClO4 Solutions at pH 2.5 using UV-vis spectrophotometry. The kinetics and mechanism of the complex-formation reactions were Studied as I function of nucleophile concentration and temperature. These reactions were also Studied in the presence and absence of micelles of sodium dodecyl sulfate (SIDS). The presence of anionic micelles accelerated complex-forination. The largest effect of micelles has been observed in the case of L-methionine. On the other hand, all increase in the ionic strength in the presence of micelles caused a decrease in the rate. The negative entropies of activation support all associative complex-formation mechanism

DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(II) terpyridine complexes

In this study, two representatives of previously synthesized ruthenium(II) terpyridine complexes, i.e., [Ru(Cl-tpy)(en)Cl][Cl] (1) and [Ru(Cl-tpy)(dach)Cl][Cl] (2), were chosen and a detailed study of the kinetic parameters of their reactivity toward L-histidine (L-His), using the UV-Vis and 1H NMR techniques, was developed. The inner molecular rearrangement from N3-coordinated L-His to the N1 bound isomer, observable in the NMR data, was corroborated by DFT calculations favoring N1 coordination by nearly 4 kcal mol−1. These two ruthenium(II) terpyridine complexes were investigated for their interactions with DNA employing UV-Vis spectroscopy, DNA viscosity measurements and fluorescence quenching measurements. The high binding constants obtained in the DNA binding studies (Kb = 104–105 M−1) suggest a strong binding of the complexes to calf thymus (CT) DNA. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (Ksv = 1.5–2.5 × 104 M−1). In fact, the results indicate that these complexes can bind to DNA covalently and non-covalently. In order to gain insight of the behavior of a neutral compound, besides the four previously synthesized cationic complexes [Ru(Cl-tpy)(en)Cl][Cl] (1), [Ru(Cl-tpy)(dach)Cl][Cl] (2), [Ru(Cl-tpy)(bpy)Cl][Cl] (3) and [Ru(tpy)Cl3] (P2), a new complex, [Ru(Cl-tpy)(pic)Cl] (4), was used in the biological studies. Their cytotoxicity was investigated against three different tumor cell lines, i.e., A549 (human lung carcinoma cell line), HCT116 (human colon carcinoma cell line), and CT26 (mouse colon carcinoma cell line), by the MTT assay. Complexes 1 and 2 showed higher activity than complexes 3, 4 and P2 against all the selected cell lines. The results on in vitro anticancer activity confirmed that only compounds that hydrolyze the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor

Studies on the reactions of [AuCl4]− with different nucleophiles in aqueous solution

In order to distinguish between the different types of reactions that can occur between Au(III) species and simple nucleophiles, including iodide, bromide, nitrite, thiourea, pyridine and dimethyl sulfoxide, spectrophotometric techniques including stopped-flow and rapid-scan measurements were employed under specific reaction conditions. All experiments were performed in a 0.4 M NaCl aqueous solution to maintain a high chloride concentration and a constant ionic strength. The temperature dependence of the observed rate constants confirmed the associative nature of the ligand substitution reactions. The redox behaviour of the Au(III) species was studied by cyclic voltammetry and confirmed the reversible redox transitions at ca. 0.38 V (SCE, E = 0.1 V s−1). Results obtained during the reaction progress were attributed to the formation of Au0. This oxidation state was observed for the reactions with thiourea, iodide and nitrite, whereas pyridine showed a potential shift only to Au(I) formation, while bromide showed potential shifts typical of ligand substitution reactions. The reaction with dimethyl sulfoxide was studied using 1H NMR and ab initio (RMP2(full)/LANL2DZp) techniques, which revealed why Au(III) does not react with sulfoxide. The results are discussed in terms of the importance of the stability of the Au(III) species in aqueous solutions of the selected salts and bases. In this way, one could differentiate between a possible three-electron inner-sphere redox process and/or a substitution process during the rapid initial step of the reactions

Substitution versus redox reactions of gold(III) complexes with L-cysteine, L-methionine and glutathione

The influence of tridentate, nitrogen donor ligands, on the stability of gold(III) complexes under physiological conditions was investigated. The interaction of [Au(terpy)Cl]2+ (terpy = 2,2′:6′2′′ terpyridine), [Au(bpma)Cl]2+ (bpma = bis(pyridyl-methyl)amine), [Au(dien)Cl]2+ (dien = diethylenetriamine) and [AuCl4]− with the biologically relevant thiols, L-cysteine (L-Cys) and glutathione (GSH), and thioether, L-methionine (L-Met), was studied using UV-Vis spectroscopy, cyclic voltammetry, 1H NMR spectroscopy and ESI-MS. In this study, the rate constants for substitution reactions between monofunctional gold(III) complexes and sulfur donor ligands in aqueous solution were determined at different initial concentrations of reactants, chloride ions, pH and constant ionic strength. The obtained second-order rate constants for the reaction with L-methionine in the absence of added chloride at pH 2.5 and 25 °C follow the sequence (7.5 ± 0.4) × 103 > (4.5 ± 0.1) × 102 > 88.3 ± 0.8 M−1 s−1 for the terpy, bpma and dien complexes, respectively, demonstrating that the substitution step could be detected prior to the reduction step. This behavior was expected due to the influence of a decreasing π-donor ability of the chelate ligands, which slows down the substitution reactions along the series of complexes studied. In order to throw more light on the mechanism of biological activity of gold(III) compounds, such a systematic study was performed for all the mentioned thiols and thioether

Kinetics and mechanism of the substitution reactions of some monofunctional Pd(II) complexes with different nitrogen-donor heterocycles

<div><p>Substitution reactions of five monofunctional Pd(II) complexes, [Pd(terpy)Cl]⁺ (terpy = 2,2′;6′,2″-terpyridine), [Pd(bpma)Cl]⁺ (bpma = bis(2-pyridylmethyl)amine), [Pd(dien)Cl]⁺ (dien = diethylenetriamine or 1,5-diamino-3-azapentane), [Pd(Me₄dien)Cl]⁺ (Me₄dien = 1,1,7,7-tetramethyldiethylenetriamine), and [Pd(Et₄dien)Cl]⁺ (Et₄dien = 1,1,7,7-tetraethyldiethylenetriamine), with unsaturated N-heterocycles such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazole, pyrazine, and imidazole were investigated in aqueous 0.10 M NaClO₄ in the presence of 10 mM NaCl using variable-temperature stopped-flow spectrophotometry. The second-order rate constants <i>k</i>₂ indicate that the reactivity of the Pd(II) complexes decrease in the order [Pd(terpy)Cl]⁺ > [Pd(bpma)Cl]⁺ > [Pd(dien)Cl]⁺ > [Pd(Me₄dien)Cl]⁺ > [Pd(Et₄dien)Cl]⁺. The most reactive nucleophile of the heterocycles is pyrazine, while the slowest reactivity is with pyrazole. Activation parameters were determined for all reactions and negative entropies of activation, Δ<i>S</i>^≠, supporting an associative mode of substitution. The reactions between [Pd(bpma)Cl]⁺ and 1,2,4-triazole, pzI, and pzBr were also investigated by ¹H NMR to define the manner of coordination. These results could be useful for better explanation of structure-reactivity relationships of Pd(II) complexes as well as for the prediction of potential targets of Pd(II) complexes toward common N-heterocycles, constituents of biomolecules and different N-bonding pharmaceutical agents.</p></div

Interactions of nitrogen-donor bio-molecules with dinuclear platinum(II) complexes

<div><p>Substitution reactions of the dinuclear Pt(II) complexes, [{Pt(en)Cl}₂(<i>μ</i>-pz)]²⁺ (<b>1</b>), [{Pt(dach)Cl}₂(<i>μ</i>-pz)]²⁺ (<b>2</b>) and [{Pt(dach)Cl}₂(<i>μ</i>-4,4ʹ-bipy)]²⁺ (<b>3</b>), and corresponding aqua analogs with selected biologically important ligands, viz<i>.</i> 1,2,4-triazole, L-histidine (L-His) and guanosine-5ʹ-monophosphate (5ʹ-GMP) were studied under <i>pseudo</i>-first-order conditions as a function of concentration and temperature using UV–vis spectrophotometry. The reactions of the chloride complexes were followed in aqueous 25 mmol L⁻¹ Hepes buffer in the presence of 40 mmol L⁻¹ NaCl at pH 7.2, whereas the reactions of the aqua complexes were studied at pH 2.5. Two consecutive reaction steps, which both depend on the nucleophile concentration, were observed in all cases. The second-order rate constants for both reaction steps indicate a decrease in the order <b>1</b> > <b>2</b> > <b>3</b> for all complexes. Also, the p<i>K</i>_a values of all three aqua complexes were determined. The order of the reactivity of the studied ligands is 1,2,4-triazole > L-His > 5ʹ-GMP. ¹H NMR spectroscopy and HPLC were used to follow the substitution of chloride in the dichloride <b>1</b>, <b>2</b>, and <b>3</b> complexes by guanosine-5ʹ-monophosphate (5ʹ-GMP). This study shows that the inert and bridging ligands have an important influence on the reactivity of the studied complexes.</p></div