This award from the Inorganic, Bioinorganic and Organometallic Chemistry Program is in the area of bioinorganic chemistry. The project deals with the synthesis and reaction chemistry of derivatives of vitamin B-12. Various derivatives of this vitamin serve as coenzymes in the catalysis of about 15 enzymic reactions in organisms ranging from bacteria to human beings. Details of two kinds of recently discovered isomerism in organocobalt derivatives of vitamin B-12 will be studied. The first involves formation of upper (beta) and lower (alpha) alkylcobalt derivatives when cobinamides (vitamin B-12 derivatives lacking the pendant axial ligand) are reductively alkylated with some, but not other alkylating agents. The reason for the different outcomes with different alkylating agents will be studied as well as the mechanism of formation of two isomers and the conditions under which the isomers can be interconverted. Preliminary results indicate that interconversion of such isomers may involve novel dialkylcobinamide species. The second type of isomerism involves formation of pairs of apparently isomeric alkylcobalt derivatives when aquocobalamin is reductively alkylated with alkoxyethyl bromides. These cannot be alpha and beta isomers, but are believed to be 2-alkoxyethyl and 1-alkoxyethyl cobalamins. The structures will be determined by NMR spectroscopy of products synthesized with isotopically enriched alkoxyethyl bromides, and the mechanism of formation of such pairs of isomers will be studied. The conditions under which the isomers are interconverted will be determined also.
