Michael B. Smith
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(b.
1946)
Visiting Professor, Universite Catholique de Louvain,
Louvain-la-Neuve, Belgium, 1986
NIH Postdoctoral Trainee, Massachusetts Institute of
Technology, 1979
Faculty Research Associate, Arizona State University,
1978
Ph.D., Purdue University, 1977
B.S., Virginia Polytechnic Institute and State University,
1969
A.A., Ferrum College, 1967
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Research
• Development of cancer targeting
fluorescent dyes.
We have synthesized a dye-conjugate that is characterized
by a nitroimidazole moiety connected to an indocyanine
green derivative (see 1). We have shown, in collaboration
with Professor Quing Zhu of the Department of Computer
and Electrical Engineering that the dye-conjugate targets
hypoxic cancerous tumors, allowing them to be detected
by fluorescence imaging. Cancerous tumors in living
mice have been detected to a depth of several centimeters.
Work continues to improve the fluorescent yield of the
dye conjugate, improve the lifetime of the dye-conjugate
in living mice and to improve the detection limits.
Work will also target dye-conjugate that not only target
the cancerous tumor, but also kill it. New generations
of the dye conjugate have been prepared with modifications
to the structure, including binding a dye-conjugate
derivative to carbon nanotubes. Work continues in this
area.
• Asymmetric synthesis and identification
of bacterial dihydroceramides from the human dental
pathogen Porphyromonas gingivalis.
We are working in collaboration with Professor Frank
Nichols of the UCONN School of Periodontology to synthesize
bioactive lipids isolated from a bacterium that lives
in the human mouth, Porphyromonas gingivalis, in order
to correlate structure with biological activity. These
lipids are identified as dihydroceramides with unusual
carbon chains relative to mammalian dihydroceramides
(see 2, 3 and 4). No single pure compound has been isolated,
but each fraction is a complex mixture of the several
structures shown, and this means that total synthesis
is required to identify the individual compounds. These
compounds induce a powerful inflammatory response in
dental disease, induce bone degeneration, and trigger
multiple sclerosis in mice. The same compounds have
been identified in plaques from atherosclerosis patients.
We are synthesizing the individual stereochemically
pure diastereomers 2, 3 and 4 in order to correlate
their chemical structures with the various biological
activity, and then provide authentic samples to Prof.
Nichols for further biological investigation.
• Using conducting polymers as
Green-Chemistry reagents,
We have shown that the known conducting polymer 5 (PEDOT)
will mediate a variety of interesting organic chemical
reactions. These include ether formation, Friedel-Crafts
alkylation with alcohols, cyclodehydration of alditols
to oxepanes and tetrahydrofuran polyols, and the cyclodehydration
of ketohexoses to the useful intermediate 5-hydroxymethylfurfural.
In addition, the polymer mediates Nazarov cyclization
of dienones, pinacol rearrangement of 1,2-diols, and
1,2-alkyl shifts of carbocations derived from alcohols.
We are exploring the Green Chemistry applications. Further,
in collaboration with Professor Greg Sotzing of the
UCONN Chemistry Department, we are examining the role
of additives in the properties of conducting polymers,
and how the chemical reactions that we have observed
play a role in conductivity. One goal of this work is
to design polymers that will have reaction characteristics
of our choice.
• Total synthesis of pancratistatin
and related phenanthridone alkaloids
Pancratistatin (7) is a phenanthridone alkaloid with
potent anticancer activity. Our synthetic strategy uses
an intramolecular Diels-Alder reaction such as the conversion
of 8 to 9 to set the requisite rings and stereochemistry.
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