The objectives of this research encompass the elucidation of the chemistry of vitamin B12 and related metal complexes, with emphasis on those aspects that are relevant to the mechanisms of coenzyme B12 promoted rearrangements. Specific research themes include: (1) The development of methods for the determination of cobalt-alkyl bond dissociation energies (including thermodynamic and kinetic methods) and the application of such methods to the measurement of cobalt-alkyl bond energies in coenzyme B12 and related compounds and to the elucidation of the electronic and steric factors that may contribute to the weakening and homolytic dissociation of such bonds. (2) The generation of organo-cobalt adducts and of free radicals related to those derived from coenzyme B12 dependent substrates, notably methylmalonyl-CoA, glutamate and Alpha-methylene-glutarate, and the examination of the possible roles of such species in coenzyme B12 dependent rearrangements. (3) The synthesis of organocobalt porphyrin compounds and comparison of the cobalt-carbon bond dissociation energies and other aspects of the chemistry of such compounds (redox chemistry, etc.) with those of the corresponding cobalamins and various B12 models. The proposed research encompasses several bioinorganic, organometallic and biochemical themes. The anticipated results of the research should contribute to a better understanding of important aspects of the mechanisms of vitamin B12 dependent processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK013339-18
Application #
3225024
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1978-04-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
18
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637