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Biological Receptor Sites
Our focus has been on the binding and recognition
of small (m.w. <250), electrically uncharged molecules. We have
been especially interested in receptors for the sense of smell in
vertebrate species. Since very little is known about these receptors,
new chemistry has been devised for in vivo study.
We can make educated
guesses about mechanisms for molecular recognition and binding specificity.
For receptors that identify small, nonpolar molecules, molecular
shape does not offer enough information for a binding site to distinguish
different compounds. Other kinds of information, including chemical
reactivity, must play a role. In the sense of smell, we have uncovered
evidence that Schiff base formation plays a role in olfactory detection
of ketone-containing odorants. This chemistry is being explored
with a number of new approaches, including Two-Step Affinity Chromatography
and Accelerator Mass Spectrometry.
This chemistry is being explored
with a number of new approaches, including Two-Step Affinity Chromatography
and Accelerator Mass Spectrometry.
Gas Phase Organic Chemistry
Electrically
charged organic molecules enjoy a vastly different environment
in the gas phase than in bulk solvent. Solvation is negligible,
and counterions are absent. Chemical reactions take place on a
timescale that is much faster than the timescale for exchange
of energy with the ambient heat bath. Despite these substantial
differences, we have found at least one major feature of gas phase
ion chemistry that bears a strong resemblance to reactions in
solution: a charged and an uncharged molecule experience encounters
of long duration, in which a variety of orientations are explored
prior to chemical reaction. Therefore, the outcome of an ionic
reaction in the gas phase is not determined by the physics of
collision so much as by the chemistry of the reactants.
Many
techniques are used at UCR to probe the stereo- and regiochemistry
of the reactions of organic ions in the gas phase, among them
EBFlow (for examining the neutral products of ionic reactions
in the gas phase) and the whole range of modern instrumental methods
in NMR and Mass Spectrometry. We have found out that SN2
displacements go by backside attack in the gas phase, just as
they do in solution. In general, we are discovering aspects of
gas phase chemistry that ought to hold true for reactions in biological
media as well.
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