Inhibition of AP-1 binding and transcription by gold and selenium involving conserved cysteine residues in Jun and Fos.

Gold(I) salts and selenite, which have diverse therapeutic and biological effects, are noted for their reactivity with thiols. Since the binding of Jun-Jun and Jun-Fos dimers to the AP-1 DNA binding site is regulated in vitro by a redox process involving conserved cysteine residues, we hypothesized that some of the biological actions of gold and selenium are mediated via these residues. In electrophoretic mobility-shift analyses, AP-1 DNA binding was inhibited by gold(I) thiolates and selenite, with 50% inhibition occurring at approximately 5 microM and 1 microM, respectively. Thiomalic acid had no effect in the absence of gold(I), and other metal ions inhibited at higher concentrations, in a rank order correlating with their thiol binding affinities. Cysteine-to-serine mutants demonstrated that these effects of gold(I) and selenite require Cys272 and Cys154 in the DNA-binding domains of Jun and Fos, respectively. Gold(I) thiolates and selenite did not inhibit nonspecific protein binding to the AP-1 site and were at least an order of magnitude less potent as inhibitors of sequence-specific binding to the AP-2, TFIID, or NF1 sites compared with the AP-1 site. In addition, 10 microM gold(I) or 10 microM selenite inhibited expression of an AP-1-dependent reporter gene, but not an AP-2-dependent reporter gene. These data suggest a mechanism regulating transcription factor activity by inorganic ions which may contribute to the known antiarthritic action of gold and cancer chemoprevention by selenium.

Sol–Gel Coordination Chemistry: Building Catalysts from the Bottom-Up

The development of synthetic routes for the tailoring of efficient silica-based heterogeneous catalysts functionalized with coordination complexes or metallic nanoparticles has become a important goal in chemistry. Most of these techniques have been based on postsynthetic treatments of preformed silicas. Nevertheless, there is an emerging approach, so-called sol–gel coordination chemistry, based on co-condensation during the sol–gel preparation of the hybrid material of the corresponding complex or nanoparticle modified with terminal trialkoxysilane groups with a silica source (such as tetraethoxysilane) and in the presence of an adequate surfactant. This method leads to the production of new mesoporous metal complex-silica materials, with the metallic functionality incorporated homogeneously into the structure of the hybrid material, improving the stability of the coordination complex (which is protected by the silica network) and reducing the leaching of the active phase. This technique also offers the actual possibility of functionalizing silica or other metal oxides for a wider range of applications, such as photonics, sensing, and biochemical functions.

Structure and chemistry of TECHNO encrustations

Using as a starting point the results giving 'traditional' growth rates as determined by the decrease of radioelements (part I) and the hypothesis of rapid formation, the different mineralogical, structure and chemical characteristics of the sample have been studied to try to understand the possible mode of formation of this encrustation. A rapid formation would account for (1) the very peculiar structure of the sample composed of oriented botryoids and the bundle-like structure of the outermost oxide layer; (2) the fact that this sample represents a substitution of a preexisting hyaloclastite; (3) the different chemical gradients, mainly iron, thorium and uranium; (4) the fact that this sample which cannot have been maintained at the sediment-water interface by bioturbation is not covered by a great thickness of sediments. On the other hand, an unsolved problem remains: Why different radionuclides used for dating give growth rates of the same order of magnitude and different 'exposition ages'.

Mineralogy and chemistry of bentonitic clays from the Wombat and Exmouth Plateaus

Bentonites (i.e., smectite-dominated, altered volcanic ash layers) were recovered in Berriasian to Valanginian hemipelagic sediments of the Wombat Plateau (Site 761) and southern Exmouth Plateau (Site 763). They are compared to coeval bentonites in eupelagic sediments of the adjacent Argo Abyssal Plain (Sites 261 and 765) and Gascoyne Abyssal Plain (Site 766). A volcaniclastic origin with dacitic to rhyolitic ash as parent material is suggested by the abundance of well-ordered montmorillonite, fresh to altered silicic glass shards, volcanogenic minerals (euhedral sanidine, apatite, and long-prismatic zircon), and volcanic rock fragments, and by a vitroclastic ultrafabric (smectitized glass shards). We distinguish (1) pure smectite bentonites with a white, pink, or light gray color, a waxy appearance, and a very homogeneous, cryptocrystalline smectite matrix (water-free composition at Site 761: 68.5% SiO2, 0.27% TiO2, 19.1% Al2O3, 3.3% Fe2O3, 0.4%-1.1% Na2O, and 0.6% K2O) and (2) impure bentonitic claystones containing mixtures of volcanogenic smectite and pyroclastic grains with terrigenous and pelagic components. The ash layers were progressively altered during diagenesis. Silicic glass was first hydrated, then slightly altered (etched with incipient smectite authigenesis), then moderately smectitized (with shard shape still intact), and finally completely homogenized to a pure smectite matrix without obvious relict structures. Euhedral clinoptilolite is the latest pore-filling or glass-replacing mineral, postdating smectite authigenesis. Volcanic activity was associated with continental breakup and rapid subsidence during the "juvenile ocean phase." Potential source areas for a Neocomian post-breakup volcanism include the Wombat Plateau, Joey and Roo rises, Scott Plateau, and Wallaby Plateau/Cape Range Fracture Zone. Westward-directed trade winds transported silicic ash from these volcanic source areas to the Exmouth Plateau into the adjacent abyssal plains. The Wombat Plateau bentonites are interpreted as proximal ash turbidites.

Organic chemistry; or, Chemistry of the carbon compounds,

I. Chemistry of the aliphatic series newly tr. and rev. from the German ed. (after Prof. Edgar F. Smiths's 3d American ed.) by Percy E. Spielman. 1916. ...II. Chemistry of the carbocyclic compounds, tr. from the 11th German ed., by E.E. Fournier d'Albe. 1922. ...III. Heterocyclic compounds, Tr. from the 11th German ed., by E.E. Fournier d'Albe. 1923.

Studies of the interaction of Potassium(I), Calcium(II), Magnesium(II), and Copper(II) with Cyclosporin A

Metal ion binding properties of the immunosuppressant drug cyclosporin A have been investigated. Complexation studies in acetonitrile solution using H-1 NMR and CD spectroscopy yielded 1:1 metal-peptide binding constants (log(10)K) for potassium(l), < 1, magnesium(II), 4.8 +/- 0.2. and calcium(II), 5.0 +/- 1.0. The interaction of copper(II) with cyclosporin A in methanol was investigated with UV/visible and electron paramagnetic resonance (EPR) spectroscopy. No complexation of copper(II) was observed in neutral solution. In the presence of base, monomeric copper(II) complexes were detected. These results support the possibility that cyclosporin A has ionophoric properties for biologically important essential metal ions. (C) 2003 Elsevier Inc. All rights reserved.

Novel diaroylhydrazine ligands as iron chelators: coordination chemistry and biological activity

The search for orally effective drugs for the treatment of iron overload disorders is an important goal in improving the health of patients suffering diseases such as beta-thalassemia major. Herein, we report the syntheses and characterization of some new members of a series of N-aroyl-N'-picolinoyl hydrazine chelators (the H2IPH analogs). Both 1:1 and 1:2 Fe-III:L complexes were isolated and the crystal structures of Fe(HPPH)Cl-2, Fe(4BBPH)Cl-2, Fe(HAPH)(APH) and Fe(H3BBPH)(3BBPH) were determined (H2PPH=N,N'-bis-picolinoyl hydrazine; H(2)APH=N-4-aminobenzoyl-N'-picolinoyl hydrazine, H(2)3BBPH=N-3-bromobenzoyl-N'-picolinoylhydrazine and H(2)4BBPH=N-(4-bromobenzoyl)-N'-(picolinoyl)hydrazine). In each case, a tridentate N,N,O coordination mode of each chelator with Fe was observed. The Fe-III complexes of these ligands have been synthesized and their structural, spectroscopic and electrochemical characterization are reported. Five of these new chelators, namely H2BPH (N-(benzoyl)-N'-(picolinoyl)hydrazine), H2TPH (N-(2-thienyl)-N'-(picolinoyl)-hydrazine), H2PPH, H(2)3BBPH and H(2)4BBPH, showed high efficacy at mobilizing Fe-59 from cells and inhibiting Fe-59 uptake from the serum Fe transport protein, transferrin (Tf). Indeed, their activity was much greater than that found for the chelator in current clinical use, desferrioxamine (DFO), and similar to that observed for the orally active chelator, pyridoxal isonicotinoyl hydrazone (H2PIH). The ability of the chelators to inhibit Fe-59 uptake could not be accounted for by direct chelation of Fe-59-Tf. The most effective chelators also showed low antiproliferative activity which was similar to or less than that observed with DFO, which is important in terms of their potential use as agents to treat Fe-overload disease.