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In our search for new anticancer and DNA interacting agents, ruthenium(III) thiosemicarbazone complexes of the type [RuCl2(EPh3)L] (where E = P/As; L = monobasic tridentate thiosemicarbazone ligand) were synthesized and characterized by physico-chemical and spectroscopic methods. All the ligands and complexes exhibit noticeable growth inhibition against fungal species and bacterial species. The interactions of these complexes with biomolecule, CT-DNA were investigated by absorbance measurement and gel electrophoresis. Absorption spectral study indicates that the ruthenium(III) complexes have an intrinsic binding constant in the range of 1.0–3.6 × 104 M−1. The complexes exhibit a remarkable DNA cleavage activity with CT-DNA in the presence of hydroxyl radical. The cleavage activity was carried out with the variation of the concentration of complexes and incubation time. Further, an in vitro cytotoxicity study of the complexes exhibited antitumor activity against the HeLa tumor cell line. This research may provide valuable insight into the interactions of metal complexes with DNA and cytotoxicity, knowledge that is an excellent back drop for the rational design of promising drugs.

The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP-1339/IT139) has entered clinical trials as the more soluble alternative to the indazolium compound KP1019. In order to get insight into its distribution and accumulation throughout a living organism, KP-1339/IT139 was administered intravenously in non-tumor bearing nude BALB/c mice and the Ru content in blood cells and plasma, bone, brain, colon, kidneys, liver, lung, muscle, spleen, stomach and thymus was determined at several time points. The Ru concentration in blood cells and plasma was found to increase slightly within the first hours of analysis, with the Ru concentration being 3-times higher in plasma compared to blood cells. The plasma samples were subjected to analysis by capillary zone electrophoresis (CZE) and size exclusion/anion exchange chromatography (SEC-IC) both coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and a large majority of the total Ru content was found attached to mouse serum albumin (MSA), confirming similar behavior to KP1019 in an in vivo setting. Within 1h, the peak ratio of approximately 1.2-1.5 Ru per albumin molecule was reached which declined to about 1 Ru per albumin molecule within 24h. Beside the MSA adduct a higher molecular weight species was observed probably stemming from MSA conjugates. In addition, the tissue samples were mineralized by microwave digestion and analyzed for their Ru content. The highest Ru levels were found in colon, lung, liver, kidney and notably in the thymus. The peak Ru concentrations in these tissues were reached 1-6h after administration and declined slowly over time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A new series of binuclear ruthenium(III) thiosemicarbazone complexes of general formula [(EPh3)2(X)2Ru-L-Ru(X)2(EPh3)2] (where E=P or As; X=Cl or Br; L=NS chelating bis(thiosemicarbazone ligands) has been synthesized and characterized by analytical and spectral (FT-IR, UV-Vis and EPR). IR spectra show that the thiosemicarbazones behave as monoanionic bidentate ligands coordinating through the azomethine nitrogen and thiolate sulphur. The electronic spectra of the complexes indicate that the presence of d-d and intense LMCT transitions in the visible region. The complexes are paramagnetic (low spin d(5)) in nature and all the complexes show rhombic distortion around the ruthenium ion with three different 'g' values (gx≠gy≠gz) at 77K. All the complexes are redox active and exhibit an irreversible metal centered redox processes (Ru(III)-Ru(III)/Ru(IV)-Ru(IV); Ru(III)-Ru(III)/Ru(II)-Ru(II)) within the potential range of 0.38-0.86V and -0.39 to -0.66 V respectively, versus Ag/AgCl. Further, the catalytic efficiency of one of the complexes [Ru2Cl2(AsPh3)4(L1)] (4) has been investigated in the case of oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of N-methylmorpholine-N-oxide(NMO) as co-oxidant. The formation of high valent Ru(V)O species is proposed as catalytic intermediate for the catalytic cycle., (Copyright © 2014 Elsevier B.V. All rights reserved.)