Cobinamides reactions

One obvious way in which to attach a nitroxide group to B12 is to simple alkylate Cob(I)aiamin with a suitable nitroxide derivative. This would result in having the nitroxide covalently bound to the corrinoid at the upper axial coordination position of the cobalt. Such a procedure is outlined in Fig. 19. In this reaction 4-bromoacetamido 2,2,6,6-tetra-methylpiperidine-N-oxyl is used to alkylate Cob(I)alamin. This results in a Co(III)-nitroxalkylcobalamin. The corresponding cobinamide can then be produced by hydrolyzing the ribose-phosphate linkage (119). 

Another chemically more interesting spin labeled B12 derivative involves coordinate attachment of the nitroxyl function to the cobalt atom of a cobinamide. Fig. 22 shows a reaction in which an alkyl cobin-amide is mixed with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. The nitroxide displaces water from the 6th coordination position very slowly and therefore this reaction is usually allowed to proceed for a few days with a large excess of nitroxide. From the properties of the coordinated nitroxide derivative discussed below, it is certain that the cobalt is coordinated by the N—O functional group. An analogous compound to that shown in Fig. 22 can be made with a similar nitroxide in which the 4-hydroxyl-group is missing. In this case the N—O-function is the only basic site on the molecule and therefore must be the position of attachment to the cobalt 119). 

The precise sequence of reactions by which cobyrinic acid (75) elaborated to cobinamide (81) and thence to vitamin B12 (64) are not known with certainty. The most probable order, suggested on the basis of the sequential production of variously amidated derivatives of cobyrinic acid by cells of P. shermanii grown in the absence of 5,6-dimethylbenzimidazole, is initiated by the amidation of the / -ring acetate carboxyl (c in Scheme 29) followed by introduction of the (R )-l-aminopropan-2-ol residue and sequential amidation of the remaining six carboxyl groups to give cobinamide (81) (66MI10400). 

The final part in the construction of adenosylcobalamin synthesis involves the transfer of a-ribazole 5 -phosphate to adenosyl-GDP-cobinamide with displacement of the GDP moiety to generate adenosylcobalamin 5 -phosphate (Figure 27). The enzyme that catalyzes this reaction is CobV in P. denitrificans and Cobs in S. The enzyme from P. denitrificans is able to accept a range of substrates including... 

Sharma VS, Pilz RB et al (2003) Reactions of nitric oxide with vitamin B12 and its precursor, cobinamide. Biochemistry 42 8900-8908... 

A characteristic reactivity of coenzyme B12 (2) in organometallic reactions is the ease of its homolytic decomposition to a 5 -deoxyadenosyl radical and cob(II)alamin (5) (Fig. 6) (26,28). From kinetic analyses of thermal decomposition reactions in solution, the homolytic bond dissociation energies of the (Co-C)-bond of 2 and 3 have been estimated as about 30 and 37 kcal mol" respectively (26,28). Accordingly, the (Co-C)-bond of 3 is considerably more resistant against homolysis than that of 2. At 110°, the thermolysis of adenosyl-cobinamide (8+) in aqueous solution occurs at only a 20 times lower rate than that of the coenzyme 2 (28). Thus, the nucleotide coordination contributes little in activating the... 

P. arabinosum and the bacteria that live in the gut of humans and animals synthesize mostly the purine-containing cobamides. If DMB is added to the feed, then the synthesis of cobalamins in the stomach of animals increases (Rickard et al., 1975). The finding of incomplete corrinoids in various bacteria and algae (Neujahr and Frires, 1966) shows that their biosynthesis may proceed with difficulty. Cobinamide, pseudo-vitamin B, factor A and factor III can act as growth factors for microorganisms if they contain a nucleotide, they are also active in enzymatic reactions in animals. 

The decomposition of alkylcobalamin by j8-elimination of H, whether by a route analogous to (18) or (20), is impossible in neopentyl and benzyl cobalamins and cobinamides. Schrauzer s group has studied the decomposition, in the absence and presence of O2, of such compounds. The slowness of the reaction under the first conditions points to reactions (14) and (26), equilibrium lying to the left in the former and the latter... 

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