Studies are proposed to help establish mechanisms of important photochemical and related oxidation reactions in biological systems, especially photodynamic tumor therapy. We will investigate the mechanisms by which photodynamic sensitizers damage organic molecules, and study reactions with biological target molecules of singlet oxygen and other reactive oxygen species. Among other techniques, these studies will use singlet oxygen luminescence, laser flash spectroscopy, conductivity, low- temperature detection of unstable primary reaction products, and specific trapping agents for reactive species. The quantitative relationship between dimol and monomol luminescence will be determined using well-characterized chemical and photochemical sources of singlet oxygen and compared with the results of chemical trapping. New phthalocyanine sensitizers for phototherapy that are well characterized and absorb strongly at useful wavelengths will be prepared. The singlet oxygen yields of these sensitizers and their ability to localize in cells will be determined. Singlet oxygen production in model autoxidation reactions will be studied. The primary products of singlet oxygen attack on electron-rich compounds such as enamines, guanosine derivatives, and other electron-rich compounds will be characterized at low temperature by NMR spectroscopy. Both singlet oxygen and hydrogen-transfer reactions of guanosine derivatives with photosensitizers will be investigated. The photooxidation of a pyrazinone produces a compound that is stable at low temperature and is a possible model for Cypridina bioluminescence; the structure of this compound will be determined and its chemiluminescence yield determined. Reactions of flavin hydroperoxide anions with some electron-rich organic compounds will be studied as models for enzymic oxygen-transfer processes and compared with the reaction of singlet oxygen. Time-resolved studies of reactions of electron-rich substrates with singlet oxygen will be carried out, and used to determine the mechanism of singlet oxygen reactions of these substrates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM020080-17A1
Application #
3269891
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1978-06-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
17
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Muller, K; Kanner, R C; Foote, C S (1990) Kinetic studies on anthralin photooxidation. Photochem Photobiol 52:445-50
Jensen, F; Foote, C S (1987) Chemistry of singlet oxygen--48. Isolation and structure of the primary product of photooxygenation of 3,5-di-t-butyl catechol. Photochem Photobiol 46:325-30