Pyrimidine and pyrazine as N-donor ligands in mercurous complexes: [Hg-2(Pym)]NO3)(2), [Hg-2(Pym)](ClO4)(2), and [Hg-2(Pyp)(2)](ClO4)(2)

Colourless single crystals of [Hg-2(Pym)](NO3)(2), [Hg-2(Pym)](ClO4)(2) and [Hg-2(Pyp)(2)](ClO4)(2) were obtained from aqueous solutions of the respective components Hg-2(NO3)(2).2H(2)O, Hg-2(ClO4)(2).6H(2)O, pyrimidine (Pym) and pyrazine (Pyp). The crystal structures were determined from single-crystal X-ray diffractometer data. [Hg-2(Pym)](NO3)(2): monoclinic, C2/c, Z = 8, a = 1607.4(2), b = 652.79(7), c = 2000.5(2) pm, beta = 103.42(2)degrees, R-all = 0.0530; [Hg-2(Pym)](ClO4)(2): orthorhombic, Pnma, Z = 4, a = 1182.7(2), b = 1662.5(2), c = 607.9(1) pm, R-all = 0.0438; [Hg-2(Pyp)(2)](ClO4)(2): orthorhombic, Aba2, Z = 4, a = 1529.39(9), b = 1047.10(14), c = 1133.49(15) pm, R-all = 0.0381. The crystal structures of [Hg-2(Pym)](NO3)(2) and [Hg-2(Pym)](ClO4)(2) contain polymeric cationic chains [Hg-2(Pym)](+) that are arranged to corrugated layers between which the anions are situated. [Hg-2(Pyp)(2)](ClO4)(2) consists of polymeric cationic layers that are built from (Hg-2)(2)(Hg-2)(2/2)(Pyp)(4) rings connected to each other; the perchlorate tetrahedra are located between these layers.

Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif

A bis-guanylhydrazone derivative of diimidazo[1,2-a:1,2-c]pyrimidine has unexpectedly been found to be a potent stabiliser of several quadruplex DNAs, whereas there is no significant interaction with duplex DNA. Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding.

Selective oxidation of a pyrimidine thioether using supported tantalum catalysts

Ta2O5-SiO2 catalysts were prepared by a sol-gel method using tetraethyl orthosilicate (TEOS) and tantalum (V) ethoxide as the sources of silicon and tantalum, and two families of quaternary ammonium salts, [CnH(2n+1)(CH3)(3)N]Br (n = 14, 16, 18) and [(CnH(2n+1))(4)N]Br (n = 10, 12, 16, 18) as surfactants. The catalysts were compared for the selective suffoxidation of 4,6-dimethyl-2-thiomethylpyrimidine using peroxide as an oxidising agent in a range of ionic liquids and organic solvents. The sol-gel catalysts were also compared with tantalum on MCM-41 prepared by grafting. The catalysts were characterized from adsorption-desorption isotherms of N-2, XRD patterns, small-angle X-ray scattering, IR spectra from adsorbed pyridine and CDCl3, XPS spectra, and Si-29 magic angle spinning (MAS) NNIR experiments. The effect of recycling on the catalyst leaching and selectivity/activity was also studied. High activities and selectivities were found in [NTf2](-) based ionic liquids and organic solvents with good recyclability of the catalyst. Tantalum was found in the solution after reaction; however, this was determined to be due to entrapment of catalyst particulates, as opposed to leaching of the active metal. (c) 2005 Elsevier Inc. All rights reserved.

Heterogeneous oxidation of pyrimidine and alkyl thioethers in ionic liquids over mesoporous Ti or Ti/Ge catalysts

Heterogeneous catalytic oxidation of a series of thioethers (2-thiomethylpyrimidine, 2-thiomethyl-4,6-dimethyl-pyrimidine, 2-thiobenzylpyrimidine, 2-thiobenzyl-4,6-dimethylpyrimidine, thioanisole, and n-heptyl methyl sulfide) was performed in ionic liquids by using MCM-41 and UVM-type mesoporous catalysts containing Ti, or Ti and Ge. A range of triflate, tetrafluoroborate, trifluoroacetate, lactate and bis(trifluoromethanesulfonyl)imide-based ionic liquids were used. The oxidations were carried out by using anhydrous hydrogen peroxide or the urea-hydrogen peroxide adduct and showed that ionic liquids are very effective solvents, achieving greater reactivity and selectivity than reactions performed in dioxane. The effects of halide and acid impurities on the reactions were also investigated. Recycling experiments on catalysts were carried out in order to evaluate Ti leaching and its effect on activity and selectivity.

p53 Mutant Human Glioma Cells Are Sensitive to UV-C-Induced Apoptosis Due to Impaired Cyclobutane Pyrimidine Dimer Removal

The p53 protein is a key regulator of cell responses to DNA damage, and it has been shown that It sensitizes glioma cells to the alkylating agent temozolomide by up-regulating the extrinsic apoptotic pathway, whereas it increases the resistance to chloroethylating agents, such as ACNU and BCNU, probably by enhancing the efficiency of DNA repair. However, because these agents induce a wide variety of distinct DNA lesions, the direct Importance of DNA repair is hard to access. Here, it is shown that the Induction of photoproducts by UV light (UV-C) significantly Induces apoptosis In a p53-mutated glioma background. This Is caused by a reduced level of photoproduct repair, resulting In the persistence of DNA lesions in p53-mutated glioma cells. UV-C-Induced apoptosis in p53 mutant glioma cells Is preceded by strong transcription and replication inhibition due to blockage by unrepaired photolesions. Moreover, the results Indicate that UV-C-induced apoptosis of p53 mutant glioma cells Is executed through the intrinsic apoptotic pathway, with Bcl-2 degradation and sustained Bax and Bak up-regulation. Collectively, the data Indicate that unrepaired DNA lesions Induce apoptosis In p53 mutant gliomas despite the resistance of these gliomas to temozolomide, suggesting that efficiency of treatment of p53 mutant gliomas might be higher with agents that Induce the formation of DNA lesions whose global genomic repair is dependent on p53. (Mol Cancer Res 2009;7(2):237-46)

Isostructural M(RL)(2)(hfac)(2) complexes with RL=5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine

5-(4-(N-tert-Butyl-N-aminoxylphenyl)) pyrimidine (RL, 4PPN) forms crystallographically isostructural and isomorphic pseudo-octahedral M(RL)(2)(hfac)(2) complexes with M(hfac)(2), M = Zn, Cu, Ni, Co, and Mn. Multiple close contacts occur between sites of significant spin density of the organic radical units. Magnetic behavior of the Zn, Cu, Ni, Co complexes appears to involve multiple exchange pathways, with multiple close crystallographic contacts between sites that EPR (of 4PPN) indicates to have observable spin density. Powder EPR spectra at room temperature and low temperature are reported for each complex. Near room temperature, the magnetic moments of the complexes are roughly equal to those expected by a sum of non-interacting moments (two radicals plus ion). As temperature decreases, AFM exchange interactions become evident in all of the complexes. The closest fits to the magnetic data were found for a 1-D Heisenberg AFM chain model in the Zn(II) complex (J/k = (-)7 K), and for three-spin RL-M-RL exchange in the other complexes (J/k = (-)26 K, (-)3 K, (-) 6 K, for Cu(II), Ni(II), and Co(II) complexes, respectively). (C) 2008 Elsevier B.V. All rights reserved.

UMP kinase from Mycobacterium tuberculosis: Mode of action and allosteric interactions, and their likely role in pyrimidine metabolism regulation

The pyrH-encoded uridine 5′-monophosphate kinase (UMPK) is involved in both de novo and salvage synthesis of DNA and RNA precursors. Here we describe Mycobacterium tuberculosis UMPK (MtUMPK) cloning and expression in Escherichia coli. N-terminal amino acid sequencing and electrospray ionization mass spectrometry analyses confirmed the identity of homogeneous MtUMPK. MtUMPK catalyzed the phosphorylation of UMP to UDP, using ATP-Mg 2+ as phosphate donor. Size exclusion chromatography showed that the protein is a homotetramer. Kinetic studies revealed that MtUMPK exhibits cooperative kinetics towards ATP and undergoes allosteric regulation. GTP and UTP are, respectively, positive and negative effectors, maintaining the balance of purine versus pyrimidine synthesis. Initial velocity studies and substrate(s) binding measured by isothermal titration calorimetry suggested that catalysis proceeds by a sequential ordered mechanism, in which ATP binds first followed by UMP binding, and release of products is random. As MtUMPK does not resemble its eukaryotic counterparts, specific inhibitors could be designed to be tested as antitubercular agents. © 2010 Elsevier Inc. All rights reserved.

New nucleoside analogues for the recognition of pyrimidine-purine inversion sites

A new nucleoside designed to enhance triplex stability has been synthesised in 15 steps starting from sugar 2. This pathway contains the sugar derivative 9 which is a useful intermediate for the introduction of other natural and unnatural bases into the 2'-aminoethoxy nucleoside containing scaffold