Dean E. Wilcox

Professor of Chemistry
Chair of the Department of Chemistry

Dean Wilcox pursued his graduate research with Edward Solomon at MIT (1979-81) and Stanford (1982-84), where he studied the binuclear copper site in the oxygen transport protein hemocyanin (1, 2), the ortho-hydroxylating enzyme tyrosinase (3) and relevant small molecule model compounds (4).

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Upon joining the Dartmouth faculty in 1984, his initial research involved studies of a) the Ni-containing enzyme urease (5, 6, 7, 8) and binuclear metallohydrolases (9), with funding from the USDA, b) EPR-characterization of paramagnetic organometallic compounds (10), and c) coordination chemistry of the Cys-rich protein metallothionein and zinc-fingers (11, 12, 13, 14, 15), with funding from the NCI. The latter research was also part of the Dartmouth Superfund Research Program, with funding from the NIEHS.

His research has also involved collaborations with Dartmouth colleagues Roger Smith (Pharmacology & Toxicology) on the biomedical chemistry of NO (16, 17, 18, 19) and Harold Swartz (Radiology) on materials for in vivo oximetry (20) and, most recently, methods for ex vivo dosimetry with fingernails (21, 22).

His current research focuses on the thermodynamics of metal-protein interactions, with funding from NSF. This has included the development of protocols for quantifying metal-binding thermodynamics with the technique of isothermal titration calorimetry (ITC) (23, 24, 25, 26), and the application of this method in studies of metal ions binding to zinc fingers, Zn-stabilized DNA-binding domains and metallothionein (27, 28, 29), His-rich proteins involved in metal transport (30, 31, 32, 33), insulin (34, 35), and metalloenzymes (36, 37).

In addition to continuing these studies, his future research is directed toward three new projects, a) developing and applying a protocol, known as redox coordination thermodynamics (RCT), which uses ITC measurements of two metal oxidation states binding to a protein to quantify the thermodynamics of reduction of the metalloprotein, b) quantifying the Cu(I)-binding thermodynamics of proteins in copper homeostasis pathways, and c) investigating metal binding and reactions of proteins in the bacterial mer pathway for mercury detoxification, in collaboration with James Omichinski of the Universite de Montreal.

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Curriculum Vitae
603-646-2874
113 Burke
HB 6128
Department:
Chemistry
Education:
B.S. University of California at Riverside
M.S. University of California at Riverside
Ph.D. Massachusetts Institute of Technology

Selected Publications

George P. Lisi, Russell P. Hughes, Dean E. Wilcox, “Coordination Contributions to Protein Stability in Metal-Substituted Carbonic Anhydrase”, Journal of Biological Inorganic Chemistry, 2016 21, 659-667.

Marcelo M. Pedroso, Fernanda Ely, Natasa Mitic, Margaret C. Carpenter, Lawrence R. Gahan, Dean E. Wilcox, James L. Larrabee, David L. Ollis, Gerhard Schenk, “Comparative investigation of the reaction mechanisms of the organophosphate-degrading phosphotriesterases from Agrobacterium radiobacter (OpdA) and Pseudomonas diminuta (OPH)”, Journal of Biological Inorganic Chemistry 2014 19, 1263-1275.

George P. Lisi, Chien Y. M. Png, Dean E. Wilcox, “Thermodynamic Contributions to the Stability of the Insulin Hexamer”, Biochemistry 2014 53, 3576-3584.

Margaret C. Carpenter and Dean E. Wilcox, “Thermodynamics of Formation of the Insulin Hexamer: Metal-Stabilized Proton-Coupled Assembly of Quaternary Structure”, Biochemistry 2014 53, 1296-1301.

Nicholas E. Grossoehme, Scott B. Mulrooney, Robert P. Hausinger, Dean E. Wilcox “Thermodynamics of Ni2+, Cu2+, and Zn2+ Binding to the Urease Metallochaperone UreE” Biochemistry 2007 46, 10506-10516.

Ruiguang Ge, Yi Zhang, Xuesong Sun, Rory M. Watt, Qing-Yu He, Jian-Dong Huang, Dean E. Wilcox, Hongzhe Sun “Thermodynamic and Kinetic Aspects of Metal Binding to the Histidine-Rich Protein, Hpn” Journal of the American Chemical Society 2006 128, 11330-11331.

Nicholas E. Grossoehme, Shreeram Akilesh, Mary Lou Guerinot, Dean E. Wilcox, " Metal Binding Thermodynamics of the Histidine-Rich Sequence from the Iron Transport Protein ITR1 from Arabidopsis thaliana", Inorganic Chemistry 2006 45, 8500-8508; 8812. 

Yi Zhang and Dean E. Wilcox, "Thermodynamic and Spectroscopic Study of Cu(II) and Ni(II) Binding to Bovine Serum Albumin" Journal of Biological Inorganic Chemistry, 2002 7, 327-337.

M. C. Carpenter, A. Shami Shah, S. DeSilva, A. Gleaton, A. Su, B. Goundie, M. L. Croteau, M. J. Stevenson, D. E. Wilcox, R. N. Austin, “Calorimetric Studies of Pb(II) and Zn(II) Binding to MT-3, a Neurologically Important Metallothionein”, Metallomics 2016 8, 605-617.

Anne M. Rich, Elisa Bombarda, Austin D. Schenk, Paul E. Lee, Elizabeth H. Cox, Anne M. Spuches, Lynn D. Hudson, Bruno Keifer, Dean E. Wilcox, "Thermodynamics of Zn2+ Binding to Cys2His2 and Cys2HisCys Zinc Fingers and a Cys4 Transcription Factor Site", Journal of the American Chemical Society 2012 134, 10405-10418.

Anne M. Spuches and Dean E. Wilcox, "Monomethylarsenite Competes with Zn2+ for Binding Sites in the Glucocorticoid Receptor", Journal of the American Chemical Society 2008 130, 8148-8149.

Colette F. Quinn, Margaret C. Carpenter, Molly L. Croteau, Dean E. Wilcox, “Isothermal Titration Calorimetry of Metal Ions Binding to Proteins”, Methods in Enzymology, Vol. 567, Andrew Feig, Ed., Burlington: Academic Press, 2016, pp. 3-21.

Destinee K. Johnson, Michael J. Stevenson, Zayed A. Almadidy, Sharon E. Jenkins, Dean. E. Wilcox, Nicholas E. Grossoehme, “Stabilization of Cu(I) for Binding and Calorimetric Measurements in Aqueous Solution”, Dalton Transactions 2015 44, 16494-16505.

Nicholas E. Grossoehme, Anne M. Spuches, Dean E. Wilcox, “Application of Isothermal Titration Calorimetry in Bioinorganic Chemistry”, Journal of Biological Inorganic Chemistry 2010 15, 1183-1191, 1193.

Yi Zhang, Shreeram Akilesh, Dean E. Wilcox, "Isothermal Titration Calorimetry Measurements of Ni(II) and Cu(II) Binding to His, GlyGlyHis, HisGlyHis and Bovine Serum Albumin: A Critical Evaluation" Inorganic Chemistry 2000 39, 3057-3064.

Xiaoming He, Steven G. Swarts, Eugene Demidenko, Ann B. Flood, Oleg Grinberg Jiang Gui, Michael Mariani, Stephen D. Marsh, Andres E. Ruuge, Jason W. Sidabras, Dmitry Tipikin, Dean E. Wilcox, Harold M. Swartz, “Development and Validation of an Ex Vivo Electron Paramagnetic Resonance Fingernail Biodosimetric Method”, Radiation Protection Dosimetry 2014 159, 172-181.

Xiaoming He, Jiang Gui, Thomas P. Matthews, Benjamin B. Williams, Steven G. Swarts, Oleg Grinberg, Jason Sidabras, Dean E. Wilcox, Harold M. Swartz, “Use of fingernails and toenails for triage dosimetry of large populations after potential exposure to ionizing radiation”, Radiation Measurements 2011 46, 882-887.

Dean E. Wilcox, Xiaoming He, Jiang Gui, Andres E. Ruuge, Hongbin Li, Benjamin B. Williams, Harold M. Swartz, “Dosimetry Based on EPR Spectral Analysis of Fingernail Clippings”, Health Physics Journal 2010 98, 309-317.

Oleg Y. Grinberg, Benjamin B. Williams, Andres E. Ruuge, Stalina A. Grinberg, Dean E. Wilcox, Harold M. Swartz, Jack H. Freed, “Oxygen Effects on the EPR Signals from Wood Charcoals: Experimental Results and a New Model”, Journal of Physical Chemistry B 2007 111, 13316-13324.

Harriet Kruszyna, John S. Magyar, Lori G. Rochelle, Michael A. Russell, Roger P. Smith, Dean E. Wilcox, “Spectroscopic Studies of Nitric Oxide (NO) Interactions with Cobalamins: Reaction of NO with Superoxocobalamin(III) Likely Accounts for Cobalamin Reversal of the Biological Effects of NO” Journal of Pharmacology and Experimental Theraputics 1998 285, 665-671.

Louis R. Cantilena Jr., Roger P. Smith, Susan Frasur, Harriet Kruszyna, Robert Kruszyna, Dean E. Wilcox, "Nitric Oxide Hemoglobin in Patients Receiving Nitroglycerin as Detected by Electron Paramagnetic Resonance Spectroscopy" The Journal of Laboratory and Clinical Medicine 1992 120, 902-907.

Dean E. Wilcox, Harriet Kruszyna, Robert Kruszyna, Roger P. Smith, "Effect of Cyanide on the Reaction of Nitroprusside with Hemoglobin: Relevance to Cyanide Interference with the Biological Activity of Nitroprusside" Chemical Research in Toxicology 1990 3, 71-76.

Robert Kruszyna, Harriet Kruszyna, Roger P. Smith, C. Dennis Thron, Dean E. Wilcox, "Nitrite Conversion to Nitric Oxide in Red Cells and Its Stabilization as a Nitrosylated Valency Hybrid of Hemoglobin" Journal of Pharmacology and Experimental Therapeutics 1987 241, 307-313.

Dean E. Wilcox, Laura L. Bennett, Elizabeth H. Cox, George Haleblian, Brian T. Hill, Eric P. Kowack, Xiaoyan Liu, Jane S. Merkel, Amy E. Palmer, Matthew C. Posewitz, Joann E. Roy, Karen E. Wetterhahn, "Interaction of Metallothionein with the Carcinogenic Metals Ni(II), Cr(VI) and As(III)" Metallothionein IV, C. D. Klaassen (Ed.); Birkhäuser, Basel, 1999; pp. 585-594.

Yin Xu and Dean E. Wilcox, "Oxidation of Zinc Finger Cysteines to Thiolsulfinate" Journal of the American Chemical Society 1998 120, 7375-7376.

Matthew C. Posewitz and Dean E. Wilcox, “Properties of the Sp1 Zinc Finger #3 Peptide: Coordination Chemistry, Redox Reactions and Metal Binding Competition with Metallothionein” Chemical Research in Toxicology 1995 8, 1020-1028.

William B. Jones, Timothy E. Elgren, Maurice M. Morelock, R. C. Elder, Dean E. Wilcox, "Technetium Metallothionein:  A Spectroscopic and EXAFS Study of 99TcO+3 Binding to Zn7-Metallothionein" Inorganic Chemistry 1994 33, 5571-5578.

F. Jon Kull, Michael F. Reed, Timothy E. Elgren, Thomas L. Ciardelli, Dean E. Wilcox, "Solid Phase Peptide Synthesis of the a and b Domains of Human Liver Metallothionein and the Neurospora crassa Metallothionein", Journal of the American Chemical Society 1990 112, 2291-2298.

Joseph A. Barrera and Dean E. Wilcox, "EPR Study of the Toluene Solution Properties of the Chromium(III)-Alkyl Complexes [CpCrMeCl]2, [Cp*CrRCl]2 (R = Me, Et, CH2SiMe3) and [Cp*CrMeBr]2: Dimer-Monomer Equilibria in Solution”, Inorganic Chemistry 1992 31, 1745-1752.

Dean E. Wilcox, “Binuclear Metallohydrolases” Chemical Reviews 1996 96, 2435-2458.

Shengke Wang, Mann H. Lee, Robert P. Hausinger, Patrick A. Clark, Dean E. Wilcox, Robert A. Scott, "Structure of the Dinuclear Active Site of Urease. X-Ray Absorption Spectroscopic Study of Native and 2-Mercaptoethanol-Inhibited Bacterial and Plant Enzymes", Inorganic Chemistry 1994 33, 1589-1593.

Michael G. Finnegan, Andrzej T. Koval, Mark T. Werth, Patrick A. Clark, Dean E. Wilcox, Michael K. Johnson, "Variable Temperature Magnetic Circular Dichroism Spectroscopy as a Probe of the Electronic and Magnetic Properties of Nickel in Jack Bean Urease" Journal of the American Chemical Society 1991 113, 4030-4032.

Patrick A. Clark, Dean E. Wilcox, Robert A. Scott, "X-ray Absorption Spectroscopic Evidence for Direct Ni-S Bonding and New Ni-Ni Interaction Upon Binding of the Competitive Inhibitor 2-mercaptoethanol to Jackbean Urease", Inorganic Chemistry 1990 29, 579-581.

Patrick A. Clark and Dean E. Wilcox, "Magnetic Properties of the Nickel Enzymes Urease, Ni-substituted Carboxypeptidase A and Ni-substituted Carbonic Anhydrase" Inorganic Chemistry 1989 28, 1326-1333.

Sylvie R. Desjardins, Dean E. Wilcox, Ronald L. Musselman, Edward I. Solomon, "Polarized, Single Crystal, Electronic Spectral Studies of Cu2Cl6-2:  Excited-State Effects of the Binuclear Interaction" Inorganic Chemistry 1987 26, 288-300.

Dean E. Wilcox, Arturo G. Porras, Yeong T. Hwang, Konrad Lerch, Marjorie E. Winkler, Edward I. Solomon,"Substrate Analogue Binding to the Coupled Binuclear Copper Active Site in Tyrosinase" Journal of the American Chemical Society 1985 107, 4015-4027.

T. David Westmoreland, Dean E. Wilcox, Michael J. Baldwin, William B. Mims, Edward I. Solomon, "Detailed Spectral Analysis of Half-Met Hemocyanins: Mixed-Valent Contributions to Electronic Properties and Structure" Journal of the American Chemical Society 1989 111, 6106-6123.

Dean E. Wilcox, John R. Long, Edward I. Solomon, "EPR Studies of the  'EPR- nondetectable' Met Derivative of Hemocyanin:  Perturbations and Displacement of the Endogenous Bridge in the Coupled Binuclear Copper Active Site" Journal of the American Chemical Society 1984 106, 2186-2194.

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Works in Progress

M. M. Pedroso, F. Ely, M. C. Carpenter, N. Mitic, L. R. Gahan, D. L. Ollis, D. E. Wilcox, G. Schenk, “Formation of the Catalytic Binuclear Active Site of Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes”, in preparation.

C. F. Quinn, D. E. Wilcox, “Thermodynamics of Metal Ions Binding to Metallothionein”, in preparation.

M. L. Croteau, D. E. Wilcox, “Thermodynamics of Cu(II) and Cu(I) Binding to Azurin: A Calorimetric Method to Quantify Metalloprotein Reduction Thermodynamics”, in preparation.

M. J. Stevenson, J. V. Schuster, D. E. Wilcox, “Thermodynamics of Metal Ions Binding to the Copper Metallochaperone HAH1”, in preparation.

H. M. Wahba, M. J. Stevenson, A. Mansour, J. Sygusch, D. E. Wilcox, J. G. Omichinski, “Structural and Biochemical Characterization of Organotin and Organolead Compounds with the Organomercurial Lyase MerB Provide Important Insight into Its Unique Mechanism of Carbon-metal Bond Cleavage”, in preparation.

M. J. Stevenson, H. M. Wahba, J. G. Omichinski, D. E. Wilcox, “Thermodynamics of Hg(II) and Other Metal Ions Binding to MerB and Cleavage of the Methyl-mercury Bond”, in preparation.