Cobalamin coenzymes models

The preceding qualitative picture requires further investigation of both the energetics and structural changes in models and cobalamins. However, if it represents a reasonable approximation of the interrelationships among structure, coordination number, and axial bond strengths, then the intermediacy of 5-coordinate ComR species in the enzymatic process involving Co" and radical chemistry of coenzyme B -dependent enzymes appears unlikely. 

A fourth possibility, which arose from our collaborative structural work on both models and cobalamins, is mechanism (4), an alteration in the dmbim position or Co—N (dmbim) bond length [119], UV spectral data have been used to suggest that the Co-dmbim bond is broken during catalysis, giving the so-called base-off (benzimidazole-unhydronated) form of the coenzyme [163]. Furthermore, some unconfirmed evidence exists that axial base-free Ado-Cbi+ is still a partially active cofactor [76]. 

Bis[2,3-butanedione dioximato(l-)] cobalt derivatives (cobaloximes(I)) appear in most respects to be good model systems for the cobalamins of the vitamin B12 coenzyme.1 The central cobalt atom exhibits three stable oxidation states... 

Studies on protein-free corrinoids and model complexes have shown that increasing the steric bulkiness around the coordinated Ca atom can cause a dramatic labilization of the Co—C bond. The protein-coenzyme adduct might contain the coenzyme in a resting state and the protein in a strained state the substrate would then switch the system into a strained coenzyme and a relaxed enzyme with little thermodynamic barrier. The strained form of the coenzyme is then in labile equilibrium with base-on cobalt(II) and the free radical. " This hypothesis, that conformational changes in cobalamin can switch chemical reactions on and off, is closely analogous with the known aspects of hemoglobin function. 

It has been proposed for the reactions of MCM and GM that the methylene radicals in the mechanisms are stabilized by magnetic interactions with low-spin Co in cob(II)alamin. " To date, the importance of such stabilization has not been established. The amount of stabilization has not allowed methylene radical intermediates such as the 5 -deoxyadenosyl radical to be observed by EPR spectroscopy. The only observable radicals to date have been the most chemically stable radicals in the mechanisms, so magnetic stabilization could not have led to leveling of the stabilities of the radical intermediates. The rates and activation parameters measured for the model radical isomerizations in Figure 24 were compatible with enzymatic rates. The results showed that participation of the cobalamin portion of the coenzyme would not be required to explain substrate isomerization. The energy of the magnetic interaction between cob(II)alamin and the free radical at the active site of MCM is 4000 G (0.37 cm ) or 1 cal mol (G. H. Reed, personal communication). This amount of energy would not be an important contribution to stabilization in a radical. 

We shall report here the synthesis of cobalt-carbon bond involved in coenzyme B12 and cobalamine, cobaloxime, and Schiff base analog models, together with some aspects of their reactivity. 

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