Research SummaryEric C. Brown
Assistant Professor
ericbrown3@boisestate.edu
SN314
(208) 426-1186
Educational Background
B.S., University of Idaho, 1997
Ph.D., Oregon State University, 2002
NIH Postdoctoral Fellow, University of Minnesota, 2003-2006
Research Summary
Proteins containing transition metal ions carry out a variety of important functions in biological systems. Consequently, understanding how these chemical transformations occur and what factors regulate their reactivity is an important research area. The focus of our research is to provide fundamental insight into the structure and function of metalloenzymes using the synthetic modeling approach. The synthetic modeling approach involves the synthesis of low molecular weight complexes that model the structural and functional units of the enzymes. Useful information such as spectroscopic and structural data and identification of possible intermediates or pathways in the enzymatic cycle can be obtained through studies of the synthetic model complexes.
An example of a system that we are currently developing model complexes for is human carbonic anhydrase II (HCA II). HCA II is an enzyme that catalyzes the reversible hydration of carbon dioxide to form bicarbonate. The enzyme has numerous physiological roles such as transporting carbon dioxide from metabolizing tissues to the lungs, regulation of pH and fluid balance within the human body. The active site of HCA II contains a mononuclear zinc center coordinated by three histidine residues and a highly acidic water molecule. An important hydrogen-bonding interaction between the zinc-bound water molecule and a neighboring threonine residue lowers the pKa of the Zn-OH2 moiety (pKa ≈ 7) such that it is deprotonated at physiological pH. In addition, the hydrogen-bonding interaction is proposed to stabilize and control the binding mode (mondentate vs. bidentate) of the unstable bicarbonate intermediate. We intend to systematically examine the impact of hydrogen-bonding on the stability and binding mode of the bicarbonate intermediate by using low molecular weight complexes that model the immediate coordination environment of the zinc ion and the H-bonding residues in the active site of HCA II. This will require the synthesis of novel ligand systems that provide an internal hydrogen bond but still allow variation of the steric properties so that tetrahedral mononuclear zinc hydroxide complexes can be isolated. We are also interested in understanding why differences in activity exist for the different substituted forms of HCA II and whether the coordination properties of the metal or hydrogen bonding interactions have a greater influence over the binding mode of the bicarbonate intermediate. To gain insight into this issue, divalent metal hydroxo complexes (Co, Cd, Ni, Mn and Cu) supported by our ligand systems will be made and their reactivity with CO2 explored.
Students will obtain multidisciplinary training in the synthesis of organic and inorganic compounds. They will also be exposed to a variety of characterization methods that will be used to characterize their model complexes and to examine their reactivity. These include X-ray crystallography and NMR, IR, UV-Vis, EPR and resonance Raman spectroscopies. Finally, students will develop an understanding of mechanism by examining the reactivity and kinetics of their model complexes with either natural or model substrates.
Publications:
1. Brown, E.C.; Johnson, B.; Palavicini, S.; Kucera, B.E.; Casella, L.; Tolman, W.B. “Modular Syntheses of Multidentate Ligands with Variable N-Donors: Applications to Tri- and Tetracopper(I) Complexes.” Submitted to J. Chem. Soc., Dalton Trans.
2. Brown, E.C.; Bar-Nahum, I.; York, J.T.; Aboelella, N.W.; Tolman, W.B. “Ligand Structural Effects on Cu2S2 Bonding and Reactivity in Side-On Disulfido-Bridged Dicopper Complexes.” Inorg. Chem. 2007, 46, 486-496.
3. York, J.T.; Brown, E.C.; Tolman, W.B. “Characterization of Complex Comprising a [Cu2(S2)2]2+ Core: Bis(μ-S22-)dicopper(III) or bis(μ-S2•-)dicopper(II)?.” Angew. Chem., Int. Ed. 2005, 44, 7745-7748.
4. Brown, E.C.; York, J.T.; Antholine, W.E.; Ruiz, E.; Alvarez, S.; Tolman, W.B. “[Cu3(μ-S)2]3+ Clusters Supported by N-Donor Ligands: Progress Towards a Synthetic Model of the Catalytic Site of Nitrous Oxide Reductase.” J. Am. Chem. Soc. 2005, 127, 13752-13753.
5. Brown, E.C.; Aboelella, N.W.; Reynolds, A.M.; Aullón, G.; Alvarez, S.; Tolman, W.B. “A New Class of (μ-η2:η2-Disulfido)dicopper Complexes: Synthesis, Characterization, and Disulfide Exchange.” Inorg. Chem. 2004, 43, 3335-3337.
6. Gable, K.P.; Brown, E.C. “Rhenium-Catalyzed Epoxide Deoxygenation.” Synlett, 2003, 2243-2245.
7. Gable, K.P.; Brown, E.C. “Kinetics and Mechanism for Rhenium-Catalyzed O-Atom Transfer from Epoxides.” J. Am. Chem. Soc. 2003, 125, 11018-11026.
8. Gable, K.P.; Brown, E.C. “Coordination of a Tethered Epoxide to a Coordinatively Unsaturated Rhenium Oxo Complex.” Organometallics 2003, 22, 3096-3101.
9. Gable, K.P.; Brown, E.C. “Efficient Catalytic Deoxygenation of Epoxides Using [Tris(3,5-dimethylpyrazolyl) hydridoborato]rhenium Oxides.” Organometallics 2000, 19, 944-946.