|
|
|
|
|
|
Abstraction of a proton from a carbon atom adjacent to the carbonyl group is a mandatory step in a variety of reactions. Thus, knowledge of the factors that control the rates and equilibria of these proton transfers is essential to understand the reactivity of carbonyl compounds. Work in our laboratory addresses both the physical organic and bioorganic aspects of the ionization of carbonyl compounds. Two projects currently in progress are summarized below.
Relative Acidities of Carbonyl Compounds. As carbonyl compounds are substrates for a multitude of biochemical reactions, the equilibrium constants for ionization (Ka) of these compounds are of particular interest. Differences in the electronic properties of the atom at position X are expected to alter carbon acidity by affecting resonance stabilization of both the carbon acid and the enolate. While structural effects on the acidity of ketones have been studied extensively, much less is known about the carbon acidity of carboxylic acid derivatives. We utilize structural systems of high intrinsic acidity, such as the 2- tetralone system (1), to determine the relative acidities of ketones, esters, thiol esters and amides.
Organic Models of Enzyme Catalysis: Electrophilic Catalysis of Enolization. A wide variety of enzymatic reactions proceed with compulsory formation of an enol or enolate intermediate. As these enzymatic processes require a relatively weak base (carboxylate or imidazole) to abstract a moderately acidic proton, the precise mechanism of labilization of these protons during catalysis is of fundamental concern. To further explore the nature of electrophilic catalysis of enolization in enzymes, we are engaged in the design, synthesis and study of organic molecules that mimic the electrophilic stabilization provided by enzymes.
Recent Publications
"Evaluation of the Internal Equilibrium Constant for 3-Oxo-D5-steroid Isomerase Using the D38E and D38N Mutants: The Energetic Basis for Catalysis" Hawkinson, D.C.; Pollack, R.M.; Ambulos, N.P., Jr. Biochemistry 1994, 33, 12172-12183.
"Is a Proton Relay Involved in the Mechanism of 3-Oxo-D5-steroid Isomerase?", Hawkinson, D.C.; Pollack, R.M. Biochemistry 1993, 32, 694-698.
"Energetics of 3-Oxo-D5-steroid Isomerase: Source of the Catalytic Power of the Enzyme", Hawkinson, D.C.; Eames, T.C.M.; Pollack, R.M. Biochemistry 1991, 32, 10849-10858.
"Kinetic Competence of an Externally Generated Dienol Intermediate with Steroid Isomerase", Hawkinson, D.C.; Eames, T.C.M.; Pollack, R.M. Biochemistry 1991, 32, 6956-6964.
Send e-mail to: dhawkins@usd.edu
USD Home Page
USD Chemistry
Department