Faculty
John P. Richard
Professor
Office: 633 Natural Sciences Complex
Phone: (716) 645-4232
Fax: (716) 645-6963
E-mail: jrichard@buffalo.edu
Lab website: http://www.acsu.buffalo.edu/~jrichard/
Information on the Richard Research Group
Education:
- B. S., Ohio State University (1974)
- Ph.D., Ohio State University (1979)
- Postdoctoral Fellow, Brandeis University (1979-82)
- Research Associate, Fox Chase Cancer Center (1982-84)
- Herchel Smith Fellow in Organic Chemistry, Cambridge University, Cambridge, England (1984-85)
Honors and Awards:
- Herchel Smith Fellowship, University of Cambridge, United Kingdom, 1984-1985
- NIH First Award, 1988.
- E. T S. Walton Visitor, University College Dublin, Ireland, 2003.
- NSF Special Creativity Award, 2007.
- Visiting Professor of Chemistry, Departamento de Química Física, Universidad de Santiago, Spain, August 2003, 2006 & 2009.
- Visiting Professor of Chemistry, Department Chemie, Ludwig-Maximilians-Universität Muenchen, Germany, 2004
- Editorial Board of Bioorganic Chemistry
- Editorial Board of The Journal of Physical Organic Chemistry.
- Coeditor of Annual Reports on the Progress of Chemistry: Organic Chemistry, 1996- 2002.
- Editor of Advances in Physical Organic Chemistry, 2000-present
- Elected Secretary, Division of Biological Chemistry, American Chemical Society, 2003-2005, 2006-2008
- Elected Vice Co-Chair and then Co-Chair Gordon Research Conference on Enzymes, Coenzymes and Metabolic Pathways, 2005, 2006
- Elected Vice-Chair and then Chair Gordon Research Conference on Isotopes in Chemistry and Biology, 2008, 2010.
- Organizing Committee, Reaction Mechanisms VII Conference, Dublin, Ireland, 2004.
- Advisory Board, IUPAC 19th International Conference on Physical Organic Chemistry (ICPOC-19), 2008
- Selected Chair of the Organizing Committee for the 22nd Enzyme Mechanisms Conference, 2011.
Specializations:
Mechanisms of enzyme-catalyzed reactions and the reactions of small molecules in solution that may be models for enzyme catalysis.
Research Summary:
The field of molecular biology requires a community of biologists who possess an intuitive understanding of how to delineate the many complex cellular and higher-order processes which occur in living systems, and of chemists and biochemists who possess the ability to determine the underlying chemical mechanism for these biological processes. Within the latter community studies of enzymes and their reaction mechanisms have long provided a unique understanding of how life functions at a molecular level.
There are many questions that can be raised about the mechanism for uncatalyzed and enzyme-catalyzed reactions of small molecules in water. What are the lifetimes of carbanion and carbenium ion intermediates of these reactions, and how does their lifetime govern the reaction mechanism? Why are some reaction mechanisms stepwise and other mechanisms concerted? What imperatives determine the chemical mechanisms for enzyme-catalyzed reactions? What is the origin of the rate acceleration for enzymatic reactions. What are the intermediates of enzyme-catalyzed reactions, and how are these species stabilized by interaction with the protein catalyst?
Research projects in progress at this time in Professor Richard's lab include: (1) The determination of the rate and equilibrium constants for addition of nucleophilic reagents to simple carbenium ions and the effect of changing carbenium ion structure on these kinetic and thermodynamic parameters. (2) The generation of biologically important enolates, and development of experimental protocol to estimate the pKas for weak carbon acids. (3) Studies on the mechanism for nonenzymatic and enzyme-catalyzed aldol addition reactions in water. (4) The determination of the mechanistic imperatives for nonenzymatic and enzyme-catalyzed aldose-ketose and allylic isomerization reactions. (5) The characterization of the transition state and intermediates of ß-galactosidase catalyzed hydrolysis of glycosides and determination of the function of essential amino-acid residues in the enzymatic reaction.
Selected Recent Publications:
- K. Toth and J. P. Richard, "Covalent Catalysis by Pyridoxal: Evaluation of the Effect of the Cofactor on the Carbon Acidity of Glycine", J. Am. Chem. Soc., 129, 3013-3021 (2007).
- T. L. Amyes and J. P. Richard, "Enzymatic Catalysis of Proton Transfer at Carbon: Activation of Triosephosphate Isomerase by Phosphite Dianion", [Hot Article] Biochemistry, 46, 5841-5854 (2007).
- J. P. Richard and K. B. Williams, "A Marcus Treatment of Rate Constants for Protonation of Ring-Substituted α-Methoxystyrenes: Intrinsic Reaction Barrier and the Shape of the Reaction Coordinate", J. Am. Chem. Soc., 129, 6952-6961 (2007).
- Chi-Tung Chiang, Marek Freindorf, Thomas Furlani, Robert L. DeLeon, John P. Richard and James F. Garvey, "Characterization of a Three Electron Interaction Between Ammonia and the Benzene Radical Cation", J. Phys. Chem., 111, 6068-6076 (2007).
- Erik R. Farquhar, John P. Richard and Janet R. Morrow, "Formation and Stability of Mononuclear and Dinuclear Eu(III) Complexes and Their Catalytic Reactivity Toward Cleavage of an RNA Analog", Inorg. Chem., 46, 7169-7177 (2007).
- John P. Richard, Wing-Yin Tsang, "A Simple Method to Determine Kinetic Deuterium Isotope Effects and Evidence that Proton Transfer To Carbon Proceeds Over and not Through the Reaction Barrier", J. Am. Chem. Soc., 129, 10330-10331 (2007).
- Krisztina Toth, Tina L. Amyes, Kui Chan, Bryant M. Wood, John A. Gerlt and John P. Richard, "Product Deuterium Isotope Effect on OMP Decarboxylase: Evidence for the Existence of a Short-Lived Carbanion Intermediate", J. Am. Chem. Soc., 129, 12946-12947 (2007).
- Tina L. Amyes and John P. Richard, "Rational Design of Transition State Analogues as Potent Enzyme Inhibitors with Therapeutic Applications", ACS Chemical Biology, 2, 711-714 (2007).
- Tina L. Amyes, Bryant M. Wood, Kui Chan, John A. Gerlt and John P. Richard, "Formation and Stability of a Vinyl Carbanion at the Active Site of Orotidine 5'-Monophosphate Decarboxylase: pKa of the C-6 Proton of Enzyme-Bound UMP", J. Am. Chem. Soc., 1574-1575 (2008).
- Juan Crugeiras, Ana Rios, Enrique Riveiros, Tina L. Amyes, Glycine Enolates: The Effect of Formation of Iminium Ions to Simple Ketones on α-Amino Carbon Acidity and a Comparison with Pyridoxal Iminium Ions", J. Am. Chem. Soc., 2041-2050 (2008).
