In addition to key aspects of B12 chemistry, both historical and recent advances in B12 biology and biochemistry are reviewed. The fascinating biological roles of B12 compounds reveal the value of Nature's choice of mononuclear, organometallic cofactors based on cobalt. The Co–C bond undergoes either heterolytic or homolytic cleavage in enzymatic processes. The intricate biological processes that depend on B12 (enzymes dependent on either methylB12 or 5′-deoxyadenosylB12 cofactors) or are necessary for B12 biochemistry (transport proteins, enzymes needed for cofactor biosynthesis) are intimately tied to the versatile cobalt coordination chemistry. B12 derivatives, with a pentadentate ligand fine-tuned by Nature to impart to the Co the necessary properties, have both structural and spectroscopic properties as well as chemical/biochemical reactivity linked to the axial ligation. The corrin ring in the equatorial plane of the methylB12 or 5′-deoxyadenosylB12 cofactors enhances the trans influence of the axial alkyl groups in comparison to the strength of this influence in simpler synthetic models. This unique enhancement of the trans influence attributable to the corrin ring is an alluring aspect of cofactor coordination chemistry. More importantly, the strong trans influence plays a prominent role in biology. The frequent involvement of three oxidation states (III, II, and I) and coordination numbers (6, 5, and 4) of the cobalt center also plays a dominant role. Also mentioned is the remarkably strong trans influence of NO in NOB12, the potential uses of B12 bioconjugation in cancer diagnosis and treatment, as well as predictions of the future vitality of the B12 field. Finally, the substrate radical rearrangement step long thought to be independent of Co participation may in fact be shown in future to have Co involvement in limited cases. Establishing such additional involvement of the Co in some enzymatic processes would raise even further the importance of this metal center.
