Mechanistic probes for radical intermediates in enzyme oxidations will be developed and applied in oxidation reactions by enzymes and their simple chemical mimics. A new class of carbon radical probes for enzyme oxidations of hydrocarbons are based on the ring opening of aryl substituted cyclopropylcarbinyl radicals; these are expected to be hypersensitive probes. The kinetics and mechanisms of ring openings of the radicals that could be formed from the probes will be studied in the P.I.'s laboratory as will oxidations of the probes by enzyme mimics. The probes and their possible oxidation products will be supplied to collaborating groups for studies with monooxygenase enzymes including soluble non-heme methane monooxygenases from microorganisms and microsomal cytochrome P-450 dependent monooxygenases. The combination of mimic and enzyme studies is expected to result in a clear delineation of the common aspects of the various enzyme catalyzed hydrocarbon oxidations that involve dioxygen. A nitrogen radical reaction kinetic scale similar to that which currently exists for carbon radicals will be developed. Neutral and charged nitrogen radicals will be produced from precursors developed by the P.l.'s group, and the kinetics of reactions will be determined by direct (laser flash) and indirect (competition) methods. The kinetic scale of nitrogen radical reactions is expected to be important for mechanistic studies of amine oxidations by enzymes. Such studies might ultimately result in new monoamine oxidase inhibitors for the treatment of depression and Parkinsons disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM048722-02
Application #
2186249
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1993-01-01
Project End
1996-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Wayne State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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