Research Areas
:: Enzyme Catalysis
Life at the cellular and higher levels results from the carefully controlled reactions of otherwise
stable organic molecules. Enzymes are large molecular weight catalysts of cellular organic and
inorganic reactions. My group is interested in understanding the mechanism for enzymatic catalysis
of reactions that proceed through unstable carbocation and carbanion reaction intermediates. In
solution, the overall activation barrier to reactions which proceed through such unstable
intermediates is the thermodynamic barrier to formation of the intermediate. The major problem faced
by enzyme catalysts is reducing the activation barrier for formation of reactive intermediates at an
enzyme active site. Our work focuses on understanding the mechanism by which reactive intermediates
for organic reactions are stabilized by interaction with the catalytic side chains at an enzyme
active site.
In recent years X-ray crystallographic determination of an enzyme crystal structure has placed
everything needed to explain catalysis by the examined enzyme in plain view. At the same time these
static structures raise questions about whether one is gifted enough to see. Such insight can only
come from the creative design of kinetic and other experiments to probe the dynamics of enzyme
action, with the state view of enzyme structure. The design of such experiments and the
interpretation of the experimental results is the prime objective of work in my laboratory.
Please learn more about the Richard group projects in this area:
:: Chemical Catalysis
Enzymes are very highly evolved examples of catalysts of chemical reactions. I am interested in
understanding chemical catalysis because this is a significant intellectual problem, and because a
broad understanding of such catalysis may lead to insight into the mechanism of enzyme action.
All of our work in this area is directed towards understanding the mechanism by which low molecular
weight organic and inorganic catalysts stabilize the transition state for the catalyzed reactions.
This has been the primary goal of our studies on electrophilic catalysis of proton and hydride
transfer, and Brønsted general acid catalysis of heterolytic bond cleavage at carbon. Studies on the
mechanism of the cleavage phosphate diesters, which are carried out in collaboration with Janet
Morrow at Buffalo, have the additional goal of using insight gained from experiments to determine
the mechanism by which metal ion complexes catalyze the cleavage of phosphate diesters to guide the
design of new metal ion complexes of enhanced catalytic activity.
Please learn more about the Richard group projects in this area:
:: Reactive Intermediates
Carbanions and carbocations have attracted an enormous amount of attention over the last
century, because these are the major intermediates of heterolytic reactions of carbon. The two
principle problems encountered in the study of the formation of highly unstable carbanions and
carbocations is the development of methods to measure equilibrium constants for reactions that
generate a vanishingly small concentration of the intermediate at chemical equilibrium; and, for
the determination of the rate constants for reaction of intermediates with halftimes as short as
a picosecond. The solution of these problems in our laboratory for the formation and reaction of
both carbocation and carbanions has allowed us harvest the wealth of useful data available to
scientists fortunate enough to enter virgin territory.
Carbocation-anion pairs are an ephemeral species in aqueous solution, because the polar solvent
water acts to attenuate the electrostatic attraction between the opposing charges. The methods
that we have developed to estimate the lifetime to these species in continuously yielding new
insight into their role as intermediates of solvolysis reactions.
Please learn more about the Richard group projects in this area:
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