Recent advances in the chemistry of vitamin B 12 and vitamin B 12 model compounds: reductive cobalt-carbon bond cleavage reactions.

The cobalt—carbon bond in alkylcobaloximes and in alkylcobalt derivatives of related chelates is reductively cleaved by thiols in mildly acidic medium, or by carbon monoxide, dithionite and stannite in alkaline solution. The reductants interact initially by trans attack of the cobalt atom, followed by the rate-determining cleavage of the Co—C bond. Cobalt-bound methyl groups are converted into methyl carbanions, or species with the reactivity of methyl carbanions, which react with protons of the medium to form methane. In the presence of CO2 detectable amounts of acetic acid are formed, in accord with this mechanism. The reductive cleavage of organocobalt complexes, derived from vitamin 12 or vitamin 12 model compounds, by thiols is correlated with available enzymological evidence on ribonucleotide reductase of Lactobacillus leichmannii. microbial methane biosynthesis of Methanobacilhis omelianckii and acetate biosynthesis by Clostridium thermoaceticum. All three enzymatic processes are envisaged to involve reductive Co—C bond cleavage reactions of coenzyme—substrate intermediates as part of the catalytic cycle. INTRODUCTION A number of bacterial enzymes catalyse the reduction of substrates utilizing corrinoid coenzymes as cofactors, e.g. in ribonucleotide reductase of Lactobacillus leichmannii', methane biosynthesis by cell extracts of organisms such as Met hanosarcina barkeri2 and Met hanobacillus omelianskii3. A probably related reaction is the synthesis of acetate from active methyl groups, as well as from methylcobalamin and carbon dioxide by extracts of Clostridium thermoaceticum4. In an attempt to devise functional nonenzymatic models of these reactions we have followed the hypothesis that corrin cofactors catalyse the reduction of these substrates by forming intermediate organocobalt compounds, which subsequently are reductively cleaved through interaction with biogenic reducing agents containing thiol groups. The fact that thiols or thioproteins are the reducing agents in nbonucleotide reductase is well established. However, the nature of the reducing agents interacting with the corrin cofactors in the remaining enzyme systems