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Sarah C. Rutan
BBSI project:Studies of synergistic
effects in complex metabolic pathways: what is the impact of an
increasing level of mixture complexity of the activity of the cytochrome
P45
A large number of drugs and toxins are
metabolized by the liver enzyme cytochrome P450. There are several
variations (isozymes) of this enzyme, with different levels of activity
towards different substrates. Although individual isozyme-substrate
reactions have been well characterized, less work has been carried
out for reactions carried out with numerous substrates and isozymes
reacting simultaneously. An example of the expected reactions for
the active ingredient in cough syrup, dextromethorphan, is shown
below.
Other research interests
Unraveling Solvation:
A Chemometric Study
This research project is aimed at developing a better understanding
of solvation in condensed phase systems. Chemometric methods in
conjunction with UV-visible, infrared and Raman spectroscopies are
used to study mixed solvents, solvated surfaces, and solutes in
contact with these phases. Three areas are targeted for study: (1)
use of vibrational and UV-visible spectroscopies and chemometric
curve resolution approaches for the characterization of mixed solvent
systems; (2) use of previously developed chemometric/solvatochromic
methods to characterize a broad range of C18 and C8 based liquid
chromatographic stationary phases; (3) combination of ab initio
and reaction field techniques to estimate and rationalize transition
energies for the solvated UV-visible probes used for the chromatographic
characterization studies. The most immediate impact of these studies
is the development of a better understanding of liquid chromatographic
separation processes. The results obtained in this work should permit
prediction of the specific retention characteristics for analytes
of interest in medical, environmental, and industrial settings.
The methodologies developed in this work have potential for impact
on other important areas to society, including the use of sorbents
for pollution remediation and for methodologies used to characterize
the surfaces of novel materials.
Characterization of
Chemical Dynamics in Complex Systems
One of the most difficult tasks in chemistry is the characterization
of reaction mechanisms and kinetics occurring in complex mixtures.
Often chemical reactions in naturally occurring environments (biological
matrices, soil, water, and oil) can not be reliably modeled by experiments
done in a "clean" laboratory experiment. The general properties
of the matrix, and the specific properties of the molecules that
are present may substantially alter the reactions of interest. In
order to understand the chemistry as it occurs in real systems,
reactions must be carried out in their native environment. It is
therefore necessary to be able to monitor concentration profiles
in complex systems, without having to resort to complex, physical
and chemical separations, that might introduce unwanted perturbations
to the system. One approach for studying these systems is to use
liquid chromatography coupled with UV-visible diode array detection
and mass spectrometry. When used to monitor chemical reactions,
this technique gives rise to three-way data arrays (i.e., absorbance
as a function of reaction time, chromatographic retention time,
and wavelength or mass/charge ratio). Three-way data analysis methods,
such as direct trilinear decomposition and alternating least squares
are being developed to extract the profiles that are characteristic
of the reacting species. These profiles are the chromatograms, spectra
and kinetic profiles for each of the species present in the reaction
mixtures, that allow structural, mechanistic and kinetic characterization
studies of a wide range of reactions. Current work is focused on
the hydrolysis reactions of the sulfonylurea herbicides. Success
of this program will lead to the ability to characterize complex
degradation reactions in-situ, and should be generalized to a wide
range of reactions of biochemical, industrial, and environmental
interest.
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