个人简介

Vice-Chair of the “Metals in Biology” Gordon Research Conference (2007) Member of the organizing committee for the 15th International Conference on Biological Inorganic Chemistry (ICBIC), Vancouver, B. C. (August, 2011) Ad Hoc Member of NIH Macromolecular Structure and Function (MSF-A) Study Section (Feb, 2005) Organizer and Chair of the "Non–heme Iron Chemistry in Biology" symposium to be held at the 227th American Chemical Society Meeting in Anaheim (March 2004) Editorial Advisory Board of "Journal of Biological Inogranic Chemistry" (1/1/04-12/31/07) Ad Hoc Member of NIH Metallobiochemistry (BMT) Study Section (Oct. 2003) Organizer of the first Ronald Breslow Award Symposium, held at the 225th ACS meeting in New Orleans (Mar. 2003) Ad Hoc Member of NIH Metallobiochemistry (BMT) Study Section (Oct. 2002) Elected Councilor of the American Chemical Society's Division of Inorganic Chemistry (2002-2004) Member of the Board of "Expert Analysts" for ChemTracts-Inorganic Chemistry (1998-2001) Member of the Board of Editors for the journal Inorganic Chemistry (1/1997- 1/2000) Member of NIH Metallobiochemistry (BMT) Study Section (1996-1999) Ad Hoc Member of NIH Metallobiochemistry (BMT) Study Section (1995) Chairman of Inorganic Chemistry for the 47th Northwest Regional ACS Meeting in Missoula, Montana, (June 17-19,1992) Member of the ACS, Inorganic Division, Nominations and Symposia Planning Committee (1991/1992) Organizer/Moderator of the 1990 Pauling Award Symposium University of California President's Postdoctoral Fellowship (1986 - 1988) National Institutes of Health Postdoctoral Fellowship (declined) National Institutes of Health Training Grant (1982 - 1983)

研究领域

Bioinorganic and Inorganic Chemistry

Transition-metal-containing enzymes (metalloenzymes) promote a number of critical biological processes ranging from the biosynthesis of neurotransmitters, and hormones, to DNA replication and repair, the conversion of electrochemical to chemical energy, and the photosynthetic production of dioxygen (O2). The molecular-level details of metalloenzyme functionImage1 emerge from several complementary lines of study, at the interface of chemistry, biology, and physics. By modeling the metal ion’s local environment and making systematic changes to this environment, one can determine, at the molecular-level, how reactivity correlates with structural, magnetic, and spectroscopic properties. The highly covalent nature of metal-thiolate bonds impart unique properties that serve to promote catalytic reactions. Thiolates favor coordinatively unsaturated geometries, stabilize higher oxidation states, facilitate electron and H-atom transfer reactions, as well as product release, and lower the activation barrier to O2 binding. Thiolate-ligated transition-metal complexes tend to be intensely colored, and low-spin, making it easy to spectroscopically monitor reactivity. The general approach used by the Kovacs lab involves the design of nitrogen- and sulfur-containing organic molecules with a molecular architecture that enforces a desired stereochemistry around the metal ion. We then examine the reactivity of the resulting synthetic transition-metal complexes, and look for correlations between structure and properties, such as spin-state and electronic structure, by systematically altering the organic framework of our ligands. Reactivity of these models is then compared on the basis of kinetic and thermodynamic parameters. Techniques used by our group include low temperature electronic absorption spectroscopy, EPR, electrochemistry, and X-ray crystallography. The Kovacs group reported the first and only examples of biomimetic superoxide reductase analogues, the only examples of metastable thiolate-ligated Fe(III)-OOH intermediates, and the first and only crystallographically characterized Mn(III)-OOR. Manganese peroxos are implicated as key intermediates in DNA repair, photosynthetic O2-evolution, and the metabolism of prostaglandins. Iron-peroxos are implicated as key intermediates in the biosynthesis of neurotransmitters, fatty acids, and steroids.

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Brines, L. M.; *Kovacs, J. A. "Understanding the Mechanism of Superoxide Reductase (SOR)," Eur. J. Inorg. Chem. 2007, 29-38. DOI: 10.1002/ejic.200600461 Dey, A.; Chow, M.; Taniguchi, K.; Lugo-Mas, P.; Davin, S. D.; Maeda, M.; *Kovacs, J. A.; *Odaka, M.; *Hedman, B.; *Hodgson, K. O.; *Solomon, E. I. "S K-edge XAS and DFT Calculations on Nitrile Hydratase: Geometric and Electronic Structure of the Non-Heme Iron Active Site," J. Am. Chem. Soc. 2006, 128, 533-541. DOI: 10.1021/ja0549695. Kennepohl, P.; Neese, F.; Schweitzer, D.; Jackson, H. L.; *Kovacs, J. A; *Solomon, E. I. "Spectroscopy of Non-Heme Iron Thiolate Complexes: Insight into the Electronic Structure of the Low-Spin Active Site of Nitrile Hydratase " Inorg. Chem. 2005, 44, 1826-1836. DOI: 10.1021/ic0487068. Theisen, R. M.; *Kovacs, J. A. "The Role of Protons in Superoxide Reduction by a Superoxide Reductase Analogue." Inorg. Chem. 2005,44, 1169-1171. DOI: 10.1021/ic048818z Theisen, R. M. ; Shearer, J.; Kaminsky W.; *Kovacs, J. A. "Steric and Electronic Control Over the Reactivity of a Thiolate–Ligated Fe(II) Complex with Dioxygen and Superoxide. Reversible m-oxo Dimer Formation " Inorg. Chem. 2004, 43, 7682–7690. DOI: 10.1021/ic0491884. *Kovacs, J. A. "Dioxygen Activation by Non–Heme Fe–Enzymes" Science, 2003, 299, 1024–1025 (invited "Perspective"). DOI: 10.1126/science.1081792 Shearer, J.; Fitch, S. B.; Kaminsky, W.; Scarrow, R. C.; *Kovacs, J. A. "How Does Cyanide Inhibit Superoxide Reductase? Insight from Synthetic FeIIIN4S Model Complexes"; Proc. Natl. Acad. of Sci. U.S.A., 2003, 100, 3671–3676. DOI: 10.1073/pnas.0637029100. Shearer, J.; Scarrow, R. C.; and Kovacs*, J. A. "Models For The Non-Heme Cysteinate-Ligated Iron Enzyme Superoxide Reductase: Observation and Structural Characterization By XAS of an FeIII-OOH Intermediate" " J. Am. Chem. Soc. 2002, 124, 11709–11717. DOI: 10.1021/ja012722b Shearer, J.; Jackson, H. L.; Rittenberg, D.; Leavy, T.; *Scarrow, R. C.; *Kovacs, J. A. " The First Example of a Nitrile Hydratase Model Complex that Reversibly Binds Nitriles." J. Am. Chem. Soc. 2002, 124, 11417-11428. DOI: 10.1021/ja012555f. Schweitzer, D.; Shearer, J.; Rittenberg, D.; Ellison, J. J.; Shoner, S. C.; Loloee, R.; Lovell, S. C.; Barnhart, D. *Kovacs, J. A. "Enhancing Reactivity via Structural Distortion," Inorg. Chem. 2002, 41, 3128–3136. DOI: 10.1021/ic0109187. Shearer, J.; Nehring, J.; Kaminsky, W.; *Kovacs, J. A "Modeling the Reactivity Properties of Superoxide Reducing Metalloenzymes With a Nitrogen and Sulfur Coordinated Iron Complex." Inorg. Chem. 2001, 40, 5483-5484. DOI: 10.1021/ic010221l. Jackson, H. L.; Shoner, S. L.; Cowen, J. A.; Lovell, S.; Barnhart, D.; *Kovacs, J. A. "Probing the Influence of Local Coordination Environment on the Properties of Fe–Type Nitrile Hydratase Model Complexes," Inorg. Chem., 2001, 40, 1646–1653. DOI: 10.1021/ic001271d. Shearer, J.; Kung, I. Y.; Lovell, S.; *Kovacs, J. A. "Why is There an "Inert" Metal Center in the Active–Site of Nitrile Hydratase? Reactivity and Ligand Dissociation From a Five Coordinate Co(III) Nitrile Hydratase Model." J. Am. Chem. Soc. 2001, 123, 463–468. DOI: 10.1021/ja002642s. Shearer, J.; Kung, I. Y.; Lovell, S.; *Kovacs, J. A. "A Co(III) Complex in a Mixed Sulfur/Nitrogen Ligand Environment: Modeling the Substrate– and Product–Bound Forms of the Metalloenzyme Thiocyanate Hydrolase." Inorg. Chem., 2000, 39, 4998–4999. DOI: 10.1021/ic0005689. Kung, I.; Schweitzer, D.; Shearer, J.; Taylor, W. D.; Jackson, H. L.; Lovell, S.; *Kovacs, J. A. "How Do Oxidized Thiolate Ligands Affect the Electronic and Reactivity Properties of a Nitrile Hydratase Model Compound?" J. Am. Chem. Soc. 2000, 122, 8299–8300. DOI: 10.1021/ja0017561. Shoner, S. C.; Nienstedt, A.; Ellison, J. J.; Kung, I.; Barnhart, D.; *Kovacs, J. A. "Structural Comparison of Thiolate–Ligated M(II)= Fe(II), Co(II), Ni(II), and Zn(II) Ions Wrapped in a Chiral Helical Ligand," Inorg. Chem., 1998, 37, 5721–5726. DOI: 10.1021/ic980882r. *Scarrow, R. C.; Strickler, B.; Ellison, J. J.; Shoner, S. C.; *Kovacs,J.A.; Cummings, J. G.; *Nelson, M. J., "X-ray Spectroscopy of Nitric Oxide Binding to Iron in Inactive Nitrile Hydratase and a Synthetic Model Compound." J. Am. Chem. Soc. 1998, 120, 9237–9245. DOI: 10.1021/ja973291t. Schweitzer, D.; Ellison, J. J.; Shoner, S. C. ; Lovell, S. ; and *Kovacs, J. A. "A Synthetic Model for the NO–Inactivated Form of Nitrile Hydratase," J. Am. Chem. Soc. 1998, 120, 10996–10997. DOI: 10.1021/ja981117e. Ellison, J. J; Nienstedt, A.; Shoner, S. C.; Barnhart, D.; Cowen, J. A.; *Kovacs, J. A. "Reactivity of Five–Coordinate Models for the Thiolate-Ligated Fe Site of Nitrile Hydratase," J. Am. Chem. Soc 1998, 120, 5691–5700. DOI: 10.1021/ja973129q. Shoner, S.; Humphreys, K. J.; Barnhart, D.; *Kovacs, J.A., "A Model for the Interaction of Alcohol with the Zinc Thiolate Site of Alcohol Dehydrogenase," Inorg. Chem. 1995, 34, 5933-5934. DOI: 10.1021/ic00128a002