K.S. Nagaraja

Abstract: Zinc, cadmium and mercury(II) complexes of creatinine of the composition M(Creat) 2 X 2 (X = Cl, Br or I) are prepared. The complexes are characterized by analytical and spectral methods. The increase in cyclic NH stretching frequency in the case of complexes (3350 cm −1 ) from that of the free ligand (3300 cm −1 ) suggested that secondary nitrogen is involved in coordination. The shift in the resonances of cyclic NH proton in the 1 H NMR and carbonyl and imine carbons in 13 C NMR when compared to the ligand indicated that cyclic nitrogen coordinates. Conductivity measurements in N, N-dimethylformamide suggested that the complexes are non-electrolytes. Thermal decomposition behaviour of the complexes is also discussed.

Abstract: Mo 2 S 4 (R 2 dtc) 2 (R = methyl, ethyl or benzyl; R 2 = pyrrolidinyl, piperidinyl or 4-morpholinyl) have been prepared starting from ammon

Abstract: A few copper(I) complexes with tetrathiomolybdates of the type A [O,lMoS41 [where A is ethylenediammonium (O.5enHz), hydrazinium (O.5-NzH6)' dimethylammonium, piperidinium, pyrrolidinium, morpholinium, tetraethylammonium, tetrabutylammonium and tetraphenylphosphonium] have been prepared and characterized. The magnetic and EPR results indicate that copper and molybdenum are in + I and + 6 oxidation states respectively. The infrared spectral results suggest the tetradentate nature ofMosl. Thecathodic peak potential observed at O.90VSCE for (NEt4)[CuMoS41 in cyclic voltammogram is assigned to the reduction of copper(I) to copper(O). The reaction of replacement of the ligand from Cu(Et2dtc)z by Moslfollowed by the reduction of Cu(II) to Cu(I), giving [CuMoS41reveals that Moslcan act as a potential antagonist to copper.

Abstract: The complex, oxoisothiocyanatobis(pyrrolidinyldithiocarbamato)molybdenum(V), MoO(NCS) (pyrroldtc) 2 was prepared. The IR spectra of the complex suggest that the thiocyanate group is attached through nitrogen and the presence of MoO 3+ moiety. The voltammograms of the complex in acetonitrile exhibited a pronounced cathodic wave at −0.23 V vs S.C.E. which was attributed to Mo(V)/Mo(IV) couple. The magnetic, epr and electrochemical studies indicate that the compound is mononuclear and molybdenum is in +5 oxidation state.

Abstract: The complexes FeLMS 4 (L = bipy or phen; M = Mo or W) were prepared and characterized. The linearity of the χ −1` M vs T plot and Mossbauer spectral parameters (δ: 0.28 mm s −1 ; E Q : 0.37 mm −1 ) of [Fe(bipy) 2 MoS 4 ] suggested that iron(II) assumes a distorted octahedral geometry with an intermediate spin state. The thiometallate acts as a bidentate chelating ligand towards iron(III), as evidenced by IR spectral results. An irreversible anodic wave observed at +1.04 V vs S.C.E. in the cyclic voltammogram of [Fe(bipy) 2 MoS 4 ] in DMSO suggested the oxidation of iron(II) to iron(III) and the reduction of the bipyridyl ligand occurs at −1.40 V.

Abstract: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper.

Abstract: Here we report that organic copper complexes can potently and selectively inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo. Several copper compounds, such as NCI-109268 and bis-8-hydroxyquinoline copper(II) [Cu(8-OHQ)(2)], can inhibit the chymotrypsin-like activity of purified 20S proteasome. In human leukemia cells, proteasome inhibition occurs within 15min after treatment, followed by apoptosis. Neither proteasome inhibition nor apoptosis occurs in non-transformed, immortalized human natural killer cells under the same treatment. Furthermore, proteasome inhibition and apoptosis induction were detected in prostate cancer cells treated with the ligand 8-OHQ alone following pre-treatment with copper(II) chloride. None of these events occurred in cells treated with copper(II) chloride alone, 8-OHQ alone (without growth in copper-enriched media), or nickel(II) chloride pre-treatment followed by 8-OHQ. Furthermore, we found that copper-mediated inhibition of purified 20S proteasome cannot be blocked by a reducing agent and that organic copper compounds do not generate hydrogen peroxide in the cells, suggesting that proteasome inhibition and apoptosis induction are not due to copper-mediated oxidative damage of proteins. Our results suggest that certain types of organic ligands could bind to tumor cellular copper, forming potent proteasome inhibitors and apoptosis inducers at copper concentrations found in tumor tissues.

Abstract: Attack by reactive oxygen species leads to a decay in phycoerythrin fluorescence emission. This phenomenon provides a versatile new assay for small molecules and macromolecules that can function as protective compounds. With 1-2 x 10(-8) M phycoerythrin, under conditions where peroxyl radical generation is rate-limiting, the fluorescence decay follows apparent zero-order kinetics. On reaction with HO., generated with the ascorbate-Cu2+ system, the fluorescence decays with apparent first-order kinetics. Examination of the major components of human urine in this assay confirms that at physiological concentrations, urate protects against both types of oxygen radicals. A novel finding is that creatinine protects efficiently by a chelation mechanism against radical damage in the ascorbate-Cu2+ system at creatinine, ascorbate, and Cu2+ concentrations comparable to those in normal urine. Urate and creatinine provide complementary modes of protection against reactive oxygen species in the urinary tract.

Abstract: A process for treating a hydrocarbon-containing feedstock is provided in which a hydrocarbon-containing feed comprising at least 20 wt.% of heavy hydrocarbons is mixed with hydrogen, hydrogen sulfide, and at least one catalyst to produce a hydrocarbon-containing product. The hydrocarbon-containing feedstock, the catalyst(s), the hydrogen sulfide, and the hydrogen are provided to a mixing zone and blended in the mixing zone at a temperature of from 375°C to 500°C and a total pressure of from 6.9 MPa to 27.5 MPa, where hydrogen sulfide is provided at a mole ratio of hydrogen sulfide to hydrogen of at least 0.5:9.5 and the combined hydrogen sulfide and hydrogen partial pressures provide at least 60% of the total pressure. A vapor comprised of hydrocarbons that are vaporizable at the temperature and pressure within the mixing zone is separated from the mixing zone, and, apart from the mixing zone, the vapor is condensed to produce a liquid hydrocarbon-containing product.

Abstract: Data on the ability of the important bioligands creatinine and creatine to form various types of complexes with different metal ions are summarized. The crucial role of the nature of the reaction medium in complex formation with these ligands is emphasized. The conditions for obtaining paramagnetic oligomeric platinum complexes of the “platinum blue” type (resulting from multistep redox and coordination processes) are presented.