tetrathiomolybdate and tungstate

Independent research is an important component of any undergraduate chemistry program. This article reports the findings of two of many undergraduate research projects directed by Ed Stiefel in the hopes that the results will be inspiring and useful to the scientific community. The neurological disorders associated with insufficient copper in Menkes disease and an excess of copper in Wilson's disease are well established; however, recent evidence suggests that copper may also be involved in other disorders, such as Alzheimer's, angiogenesis, and prion diseases. The exact role of copper, however, is uncertain. This study examines the role of copper and zinc in the formation of protein deposits and the chelation and removal of the metal ions to reverse the process. The bovine serum albumin (BSA) protein forms a precipitate after the addition of approximately 6 copper(II) atoms or 8 zinc(II) atoms. Other metal ions, such as Ca(II), Al(III), Ni(II), and Co(II), did not precipitate the BSA even when the metal ion to BSA ratios were in excess of 1000. The copper and zinc protein precipitates returned to solution after addition of the chelating agents, ethylenediaminetetraacetic acid (EDTA) or tetrathiometallates [(MS(4)(2-)), where M=Mo, W]. Two new choline and acetylcholine tetrathiomolybdate and tetrathiotungstate chelating agents have been synthesized and characterized. The infrared (IR) and X-ray crystal structures of the complexes revealed that the (MS(4)(2-)) cores had approximate T(d) symmetry in the choline (Ch) salts and C(2v) symmetry in the acetylcholine (AcCh) salts. The AcCh salts hydrolyzed more slowly than the ammonium or Ch salts and the tetrathiotungstate salts hydrolyzed approximately two orders of magnitude more slowly than the tetrathiomolybdate salts. The slower hydrolysis of tetrathiotungstate may make it more useful as an inorganic reagent and therapeutic agent.

Topics: Acetylcholine; Aluminum; Animals; Calcium; Cattle; Chelating Agents; Chemical Precipitation; Choline; Cobalt; Copper; Crystallography, X-Ray; Edetic Acid; Hydrolysis; Metals; Molybdenum; Nickel; Serum Albumin, Bovine; Spectrophotometry, Ultraviolet; Tungsten Compounds; Zinc

Molybdate- and ATP-dependent in vitro synthesis of the iron-molybdenum cofactor (FeMo-co) of nitrogenase requires the protein products of at least the nifB, nifN, and nifE genes. Extracts of FeMo-co-negative mutants of Klebsiella pneumoniae and Azotobacter vinelandii with lesions in different genes can be complemented for FeMo-co synthesis. Both K. pneumoniae and A. vinelandii dinitrogenase (component I) deficient in FeMo-co can be activated by FeMo-co synthesized in vitro. Properties of the partially purified dinitrogenase activated by FeMo-co synthesized in vitro were comparable to those of dinitrogenase from the wild-type organism; e.g., ratios of acetylene- to nitrogen-reduction activities, as well as those of acetylene reduction activities to EPR spectrum peak height at g = 3.65, were very similar. A. vinelandii mutants UW45 and CA30 have mutations in a gene functionally equivalent to nifB of K. pneumoniae.

Topics: Acetylene; Adenosine Triphosphate; Azotobacter; Bacterial Proteins; Cell-Free System; Chloramphenicol; Electron Spin Resonance Spectroscopy; Enzyme Activation; Ferredoxins; Genes, Bacterial; Genetic Complementation Test; Klebsiella pneumoniae; Molybdenum; Molybdoferredoxin; Nitrogen Fixation; Nitrogenase; Operon; Protein Processing, Post-Translational; Tungsten; Tungsten Compounds; Vanadates; Vanadium