Lisa M. BerreauLisa M. Berreau

Associate Professor
Inorganic Chemistry
B.S., 1990, Mankato State University
Ph.D., 1994, Iowa State University
Postdoctoral, 1995-98, University of Minnesota
435.797.1625 berreau@cc.usu.edu
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Transition metal ions are essential components of many biological systems. In metalloenzymes, metal centers are used to catalyze numerous chemical processes. We are interested in understanding
how these processes occur and how features associated with the metal center influence the overall observed chemistry. Our approach toward understanding metalloenzyme systems involves the synthesis of model complexes that are specifically designed to mimic fundamental structural, spectroscopic, and reactivity features of the metalloenzyme active site. Through comprehensive studies of these model complexes, we hope to gain an understanding of the chemical principles that control the structure and function of metalloenzymes. Summarized below are two current areas
of interest in our group:

Bioinorganic Chemistry of Nitrogen/Sulfur Ligands Possessing Internal Hydrogen Bond Donors. In this project, we are interested in gaining insight into the fundamental chemical and mechanistic features of the reaction pathways of enzymes that contain at their active site a nitrogen/sulfur-ligated divalent metal ion possessing a bound hydroxo/aquo moiety. Enzymes of this class catalyze a diverse array of chemical transformations including the oxidation of alcohols (liver alcohol dehydrogenase, LADH), the hydration of CO2 (carbonic anhydrases), and the hydrolytic cleavage of amides (bacteriophage T7 lysozyme and peptide deformylase). Importantly, an additional structural component found in the active site of several of these enzymes is an amino acid residue(s) capable of forming a hydrogen bond(s) to a metal-bound hydroxide, substrate, or product during catalytic turnover. Because the reactions catalyzed by these systems are of synthetic and technological utility, studies directed at examining novel molecules and reaction pathways relevant to these enzymes will not only complement our understanding of the biological systems, but will also provide insight into how biomimetic features (e.g., hydrogen bonding) may be utilized in new synthetic catalysts. Therefore, with the goal of elucidating fundamental structure/function relationships relevant to biological nitrogen/sulfur-ligated divalent metal sites, we have initiated a project directed at examining the bioinorganic chemistry of a novel family of nitrogen/sulfur ligands possessing internal hydrogen bond donors. Using first generation members of this family, we have prepared and structurally characterized the first examples of nitrogen/sulfur-ligated zinc hydroxide complexes, novel molecules that are stabilized through hydrogen bonding interactions, and that exhibit reactivity toward biologically relevant substrates including alcohols, CO2, and amides. Our current work in this area is focused on: (1) utilizing our novel ligand systems in attempts to synthesize, comprehensively characterize, and examine the hydrogen bonding and hydride transfer properties of nitrogen/sulfur-ligated zinc alkoxide complexes, (2) determining the structural, spectroscopic, and hydrogen bonding properties of nitrogen/
sulfur-ligated zinc and cadmium complexes possessing a variety of bound anions, including bicarbonate species, (3) elucidating the chemical, kinetic, and mechanistic details of formamide and alkylamide cleavage reactions mediated by N/S-ligated zinc complexes, (4) preparing and examining the zinc bioinorganic chemistry of new NS2 and N2S ligands possessing an internal hydrogen bond donor; and (5) isolating, comprehensively characterizing, and examining the preliminary formamide cleavage properties of nitrogen/sulfur-ligated Fe2+, Ni2+, and Co2+ hydroxide complexes.

Our research in bioinorganic chemistry involves both synthetic inorganic and organic chemistry. We employ numerous techniques to characterize our model complexes including X-ray crystallography and electronic, IR, NMR, and EPR spectroscopies. Finally, we examine the reactivity of the model complexes with biologically relevant substrates with an emphasis on identifying the chemical principles that control metalloenzyme structure and function.

Selected Publications

L.M. Berreau, "Bioinorganic Chemistry of Group 12 Complexes Supported by Tetradentate Tripodal Ligands having Internal Hydrogen Bond Donors," Eur. J. Inorg. Chem. 2006, 273-283

Allred, R. A.; Doyle, K.; Arif, A. M.;  Berreau, L. M., “Solvent Effects on the Structural and Formyl Substrate Reactivity Properties of a Nitrogen/Sulfur-ligated Zinc Hydroxide Complex,” Inorg. Chem. 2006, 45, 4097-4108.

Berreau, L. M., “Bioinorganic Chemistry of Group 12 Complexes Supported by Tetradentate Tripodal Ligands having Internal Hydrogen Bond Donors,” Eur. J. Inorg. Chem. 2006, 273-283.

Berreau, L. M.;  Saha, A.; Arif, A. M. “Thioester Hydrolysis Reactivity of Binuclear Zinc Hydroxide Complexes: Investingating Reactivity Relevant to Glyoxalase II Enzymes,” Dalton Trans. 2006, 183-192.

Szajna, E.; Arif, A. M.; Berreau, L. M. “Aliphatic Carbon-Carbon Bond Cleavage Reactivity of a Mononuclear Ni(II) Cis-?-Keto-Enolate Complex in the Presence of Base and O2: A Model Reaction for Acireductone Dioxygenase (ARD),” J. Am. Chem. Soc. 2005, 127, 17186-17187.

Szajna, E.; Makowska-Grzyska, M. M.;  Wasden, C. C.; Arif,A. M.; Berreau, L.M. “A Deprotonated Intermediate in the Amide Methanolysis Reaction of a N4O-ligated Mononuclear Zinc Complex,” Inorg. Chem. 2005, 44, 7595-7605.