Zinc is essential to all forms of life and is the second most abundant trace element in the human body. Correspondingly, zinc participates in a wide variety of biological processes, which include carbohydrate, lipid, protein and nucleic acid synthesis, regulation, and degradation. Zinc is, therefore, an indispensable element for effective growth and development, with deficiency resulting in organ malformations. In order to be able to understand fully the consequences of zinc deficiency, and hence suggest possible remedies, it is most essential to understand the bioinorganic chemistry of zinc.
The aim of this proposal is to define more fully the bioinorganic chemistry of zinc with respect to a selection of zinc enzymes, which include carbonic anhydrase, carboxypeptidase, thermolysis and liver alcohol dehydrogenase. Specifically, the bioinorganic chemistry of zinc will be delineated by studying the chemistry of synthetic analogs, i.e. simple molecules that are intended to mimic both the structure and function of the active sites of zinc enzymes. Synthetic analogs are more amenable to structural, spectroscopic, and mechanistic studies than the enzymes themselves, so that definitive investigations of these systems will allow considerable insight into the mechanism of action of the enzymes to be ascertained. The results of these studies could significantly improve our understanding of the bioinorganic chemistry of zinc and consequently could be of considerable importance in providing a rational basis of curing diseases resulting from zinc deficiency.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM046502-05
Application #
2872668
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1993-08-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Kreider-Mueller, Ava; Quinlivan, Patrick J; Owen, Jonathan S et al. (2017) Tris(2-mercaptoimidazolyl)hydroborato Cadmium Thiolate Complexes, [TmBut]CdSAr: Thiolate Exchange at Cadmium in a Sulfur-Rich Coordination Environment. Inorg Chem 56:4644-4654
Yurkerwich, Kevin; Quinlivan, Patrick J; Rong, Yi et al. (2016) Phenylselenolate Mercury Alkyl Compounds, PhSeHgMe and PhSeHgEt: Molecular Structures, Protolytic Hg-C Bond Cleavage and Phenylselenolate Exchange. Polyhedron 103:307-314
Chakrabarti, Neena; Ruccolo, Serge; Parkin, Gerard (2016) Cadmium Compounds with an [N3C] Atrane Motif: Evidence for the Generation of a Cadmium Hydride Species. Inorg Chem 55:12105-12109
Palmer, Joshua H; Parkin, Gerard (2015) Protolytic cleavage of Hg-C bonds induced by 1-methyl-1,3-dihydro-2H-benzimidazole-2-selone: synthesis and structural characterization of mercury complexes. J Am Chem Soc 137:4503-16
Kreider-Mueller, Ava; Quinlivan, Patrick J; Rong, Yi et al. (2015) Exchange of Alkyl and Tris(2-mercapto-1-t-butylimidazolyl)hydroborato Ligands Between Zinc, Cadmium and Mercury. J Organomet Chem 792:177-183
Kreider-Mueller, Ava; Quinlivan, Patrick J; Owen, Jonathan S et al. (2015) Synthesis and structures of cadmium carboxylate and thiocarboxylate compounds with a sulfur-rich coordination environment: carboxylate exchange kinetics involving tris(2-mercapto-1-t-butylimidazolyl)hydroborato cadmium complexes, [Tm(Bu(t))]Cd(O2CR). Inorg Chem 54:3835-50
Palmer, Joshua H; Parkin, Gerard (2015) Influence of Benzannulation on Metal Coordination Geometries: Synthesis and Structural Characterization of Tris(2-mercapto-1-methylbenzimidazolyl)hydroborato Cadmium Bromide, {[Tm(MeBenz)]Cd(?-Br)}2. J Mol Struct 1081:530-535
Rong, Yi; Palmer, Joshua H; Parkin, Gerard (2014) Benzannulated tris(2-mercapto-1-imidazolyl)hydroborato ligands: tetradentate ?4-S3H binding and access to monomeric monovalent thallium in an [S3] coordination environment. Dalton Trans 43:1397-407
Palmer, Joshua H; Parkin, Gerard (2014) Synthesis and Structural Characterization of 1-Arylimidazole-2-thiones and N,N'-Aryldiethoxyethylthioureas with Electronically Diverse Substituents: A Manifold of Hydrogen Bonding Networks. New J Chem 38:4071-4082
Palmer, Joshua H; Parkin, Gerard (2014) Synthesis and structural characterization of tris(2-mercapto-1-methylbenzimidazolyl)hydroborato cadmium halide complexes, {[Tm(MeBenz)]Cd(?-Cl)}2 and [Tm(MeBenz)]CdI: a rare example of cadmium in a trigonal bipyramidal sulfur-rich coordination environment Dalton Trans 43:13874-82

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