Methylation-metalation, metal-nucleotide

Vitamin B12 (Fig. 1) is defined as a group of cobalt-containing conoids known as cobalamins. The common features of the vitamers are a corrin ting (four reduced pyrrole rings) with cobalt as the central atom, a nucleotide-like compound and a variable ligand. Vitamin B12 is exceptional in as far as it is the only vitamin containing a metal-ion. The vitamers present in biological systems are hydroxo-, aquo-, methyl-, and 5 -deoxyadenosylcobalamin. 

The NMR results show that, in the case of 3 and 5 nucleotides, the binding of metal, or at least copper, does occur at Nj for adenine and guanine and at Ni for cytosine very little binding of copper occurs in thymine, the methyl derivative of uracil. NMR studies have also shown us that in the polymeric nucleic acids binding occurs generally in the same position as in these monomers. For example, in polyadenylic acid, the binding is also at Nj, and in polycytidylic acid it is at Ni. 

The cobalt-bound methyl group of methyl-Co -corrins can be readily abstracted by nucleophiles or by electrophiles, as well as by radicaloid metal centers and radicals (Figs. 7 and 8) (32,34). A unique radical methylation (see Fig. 7) has been implied specifically in the biosynthesis of fosfomycin in a Streptomyces strain (10,35), as well as in other biosynthetic transformations (36). A reversible methyl group transfer occurs rapidly in aqueous solution between methyl-Co -cobinamide (9+) and cob(I)alamin (6 ), and at equilibrium, methylcobalamin (3) and Co -cobinamide (10) prevail. From such methyl transfer equilibria, the nucleotide coordination in 3 was shown to stabilize 3 by ca. 4 kcal mol" against abstraction of the cobalt-bound methyl group by nucleophiles, to activate 3 for the abstraction of the cobalt-bound methyl group by electrophiles, but to hardly... 

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