M.R. Udupa

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: The title compound Te II LI [L = diethyl dithiocarbamate, (C 2 H 5 ) 2 NCS − 2 ] was synthesized by the reduction of Te IV L 2 I 2 with elemental tellurium. Its structure has been determined and is found to be polymeric, with I being the bridging ligand. The polymeric chain adopts a helical configuration which runs parallel to the c -axis of the tetragonal unit cell. Each tellurium is bonded to two sulphurs of a chelating dithiocarbamate group and to two iodines in a planar configuration. The bond distances of TeS(1), TeS(2), TeI and TeI′ are 2.536(4), 2.483(5), 3.108(1) and 3.279(1) A, respectively, and the bond angles of ITeS(1), S(1)TeS(2), S(2)TeI′ and I′TeI are 149.6(2), 70.7(2), 151.1(2) and 129.2(2)°, respectively.

Abstract: The title compound TeIVLI3 [L = diethyldithiocarbamate, (C2H5)2NCS−2], is the first example of a mixed halide-dithiocarbamate complex of TeIV with halide to a dithiocarbamate ratio of 3:1. Two different methods have been employed for the preparation of this compound. The first method involves the ligand exchange reaction between TeL2 and TeI4. The second method is the oxidative addition of iodine on TeIILI. The structure of the title compound has been determined and it is found to be polymeric with iodine being the bridging ligand. The polymer is made up of interlinking of edge-sharing pentagonal bipyramidal dimers, which are stacked along a axis of the triclinic unit cell. The three TeI distances are TeI (1) 2.982 (1), TeI (2) 2.90 (1) and TeI (3) 2.872 (1) A, and together with two TeS and two intermolecular TeI interactions complete the seven coordination with a distorted pentagonal bipyramidal geometry around each tellurium.

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: Bromo- and chloro-susbtituted tellurium(II) dithiocarbamate complexes were prepared by the reaction of iododiethyldithiocarbamatotellurium(II), dissolved in dichloro-methane, with a suspension of their respective silver halide. The structure determination reveals the orthorhombic crystals of the complexes to be isomorphous, having halide-bridged polymeric structures. The polymeric chain adopts a helical configuration with the period of the helix being the length of the a -axis. Each tellurium has a TeS 2 X 2 coordination. The TeBr and TeCl distances observed in the complexes are 2.867(3) and 2.686(2) A, respectively and this structure is similar to that of Te{(C 2 H 5 ) 2 NCS 2 }I.

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: Selenium to iodine contacts ranging from the sum of the Se and I van der Waals distances to strong covalent bonds are reviewed with the help of recent structural determinations of compounds exhibiting SeI distances from 384 to 244 pm, with emphasis on ‘less clear-cut’ cases, in terms of different extents of ‘hypervalent’ 3c–4e (10-Se-3) and (10-I-2) interactions. Within a continuum of SeI interactions from undisturbed single bonds via n->σ*(SeI) interactions and typical 3c–4e XSeI or SeIX systems to van der Waals contacts, any desired SeI distances can be tuned by an appropriate choice of the particular substituents and ligands attached to the SeI moiety.

Abstract: The 3 centre-4 electrons (3c-4e) and the donor/acceptor or charge-transfer models for the description of the chemical bond in linear three-body systems, such as I3– and related electron-rich (22 shell electrons) systems, are comparatively discussed on the grounds of structural data from a search of the Cambridge Structural Database (CSD). Both models account for a total bond order of 1 in these systems, and while the former fits better symmetric systems, the latter describes better strongly asymmetric situations. The 3c-4e MO scheme shows that any linear system formed by three aligned closed-shell species (24 shell electrons overall) has reason to exist provided that two electrons are removed from it to afford a 22 shell electrons three-body system: all combinations of three closed-shell halides and/or chalcogenides are considered here. A survey of the literature shows that most of these three-body systems exist. With some exceptions, their structural features vary continuously from the symmetric situation showing two equal bonds to very asymmetric situations in which one bond approaches to the value corresponding to a single bond and the second one to the sum of the van der Waals radii of the involved atoms. This indicates that the potential energy surface of these three-body systems is fairly flat, and that the chemical surrounding of the chalcogen/halogen atoms can play an important role in freezing different structural situations; this is well documented for the I3– anion. The existence of correlations between the two bond distances and more importantly the linearity observed for all these systems, independently on the degree of their asymmetry, support the state of hypervalency of the central atom.