Biomolecular Interactions of Cytotoxic Ruthenium Compounds with Thiosemicarbazone or Benzothiazole Schiff Base Chelates.

Herein we illustrate the formation and characterization of new paramagnetic ruthenium compounds, trans-P-[RuCl(PPh3 )2 (pmt)]Cl (1) (Hpmt=1-((pyridin-2-yl)methylene)thiosemicarbazide), trans-P-[RuCl(PPh3 )2 (tmc)]Cl (2) (Htmc=1-((thiophen-2-yl)methylene)thiosemicarbazide) and a diamagnetic ruthenium complex, cis-Cl, trans-P-[RuCl2 (PPh3 )2 (btm)] (3) (btm=2-((5-hydroxypentylimino)methyl)benzothiazole). Agarose gel electrophoresis experiments of the metal compounds illustrated dose-dependent binding to gDNA by 1-3, while methylene blue competition assays suggested that 1 and 2 are also DNA intercalators. Assessment of the effects of the compounds on topoisomerase function indicated that 1-3 are capable of inhibiting topoisomerase I activity in terms of the ability to nick supercoiled plasmid DNA. The cytotoxic activities of the metal complexes were determined against a range of cancer cell lines versus a non-tumorigenic control cell line, and the complexes were, in general, more cytotoxic towards the cancer cells, displaying IC50 values in the low micromolar range. Time-dependent stability studies showed that in the presence of strong nucleophilic species (such as DMSO), the chloride co-ligands of 1-3 are rapidly substituted by the former as proven by the suppression of the substitution reactions in the presence of an excess amount of chloride ions. The metal complexes are significantly stable in both DCM and an aqueous phosphate buffer containing 2 % DMSO.

Structural, kinetics and mechanistic studies of transfer hydrogenation of ketones catalyzed by chiral (pyridyl)imine nickel(ii) complexes.

The chiral synthons (S-)-1-phenyl-N-(pyridine-2-yl)ethylidine)ethanamine (L1), (R-)-1phenyl-N-(pyridine-2-yl)ethylidine))ethanamine (L2) (S)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L3), and (R)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L4) were synthesized in good yields. Treatments of L1-L4 with NiBr2(DME) and NiCl2 precursor afforded dinuclear complexes [Ni2(L1)4-µ-Br2]NiBr4 (Ni1), [Ni2(L2)4-µ-Br2]NiBr4 (Ni2), [Ni2(L3)4-µBr2]Br2 (Ni3), [Ni2(L4)4-µ-Br2]NiBr4 (Ni4) and [Ni(L4)2Cl2] (Ni5). The identities of the compounds were established using NMR, FT-IR and EPR spectroscopy, mass spectrometry, magnetic moments, elemental analysis and single crystal X-ray crystallography. The dinuclear dibromide nickel complexes dissociate into mononuclear species in the presence of strongly coordinating solvents. Compounds Ni1-Ni5 displayed moderate catalytic activities in the asymmetric transfer hydrogenation (ATH) of ketones, but with low enantiomeric excess (ee%). Both mercury and substoichiometric poisoning tests pointed to the homogeneous nature of the active species with the partial formation of catalytically active Ni(0) nanoparticles. Low resolution mass spectrometry analyses of the intermediates supported a dihydride mechanistic pathway for the transfer of hydrogenation reactions.

Small molecular, macromolecular, and cellular chloramines react with thiocyanate to give the human defense factor hypothiocyanite.

Thiocyanate reacts noncatalytically with myeloperoxidase-derived HOCl to produce hypothiocyanite (OSCN(-)), thereby potentially limiting the propensity of HOCl to inflict host tissue damage that can lead to inflammatory diseases. However, the efficiency with which SCN(-) captures HOCl in vivo depends on the concentration of SCN(-) relative to other chemical targets. In blood plasma, where the concentration of SCN(-) is relatively low, proteins may be the principal initial targets of HOCl, and chloramines are a significant product. Chloramines eventually decompose to irreversibly damage proteins. In the present study, we demonstrate that SCN(-) reacts efficiently with chloramines in small molecules, in proteins, and in Escherichia coli cells to give OSCN(-) and the parent amine. Remarkably, OSCN(-) reacts faster than SCN(-) with chloramines. These reactions of SCN(-) and OSCN(-) with chloramines may repair some of the damage that is inflicted on protein amines by HOCl. Our observations are further evidence for the importance of secondary reactions during the redox cascades that are associated with oxidative stress by hypohalous acids.