Corrin rings

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

The structure of the diamagnetic, cherry-red vitamin B12 is shown in Fig. 26.6 and it can be seen that the coordination sphere of the cobalt has many similarities with that of iron in haem (see Fig. 25.7). In both cases the metal is coordinated to 4 nitrogen atoms of an unsaturated macrocycle (in this case part of a corrin ring which is less symmetrical and not so unsaturated as the porphyrin in haem) with an imidazole nitrogen in the fifth position. A major... 

Figure 26.6 Vitamin B12 (a) a corrin ring showing a square-planar set of N atoms and a replaceable H, and (b) simplified stmcture of B12. In view of the H displaced from the corrin ring, the Co-C bond, and the charge on the ribose phosphate, the cobalt is formally in the - -3 oxidation state. This and related molecules are conveniently represented as r...

Incorporation of cobalt into the corrin ring system modifies the reduction potentials of... 

A related phenomenon, apparently caused by interaction of the organo-ligand with the corrin ring and its substituents, is the absence of free rotation around the Co—C bond revealed by the nonequivalence of the a and/or jS-protons in the NMR spectra of -propyl- and isopropylcobin-amide and 5-deoxyadenosylcobalamin and cobinamide, though free rotation occurs in ethylcobinamide (88, 35, 20). 

Isomers are, of course, possible when the equatorial ligand lacks a plane of symmetry, as in the corrinoids [see (HI)]. All the acetamide side chains project to one side of the corrin ring, which we shall call the upper side, and all the propionamide side chains and the nucleotide side chain to the lower side. Isomers are then theoretically possible whenever the two axial ligands are different, and their existence has been shown experimentally for corrinoids where one axial ligand is CN , Me, or Et and the other is H2O or is absent [for further details see Section 8.2 of ref. (136)]. Salen and BAE also show minor deviations from planarity due to the bending of the two halves (mentioned above in Section II,B,2) and to torsion about the C—C bonds in the ethylene bridge (see references in Table I), but these are not expected to give rise to separable isomers. 

The photochemically active bands of methylcobalamin have been identified as the intense hands due to -n—n transitions within the conjugated corrin ring, and the following quantum yields (< ) were obtained A = 490 nm, Similar quantum yields ( = 0.3-0.5) were also obtained for the photolysis of methylcobalamin in acid, where the base has been displaced and protonated, and the complex is present as a mixture of the methylaquo and five coordinate methyl complexes (/40). The effect of varying the second axial ligand on the rate of photolysis by white light has also been studied (134). 

Theoretical studies that has investigated the homolysis step in different enzymatic systems [68-70] reveal that small models comprising only the corrin ring and two ligands are insufficient and that inclusion of more amino acids are essential to stabilize the radical intermediates. Recently, a QM/MM study of the initial phase of the glutamate mutase-catalyzed reaction found a large electrostatic stabilization by the surrounding protein [70], In our study of MCM we employed the ONIOM QM MM approach to reveal the role of the protein in the rupture of the Co—C5 bond [29],... 

Cobalamin chemistry is the best-established area of cobalt biological chemistry. The 15-membered tetraazamacrocyclic corrin ring (incorporating four pyrrole residues) is the binding site for... 

Naturally, the biosynthesis of cobalamins themselves require delivery of Co ions at a particular point in the reaction scheme. Cobaltochelatase catalyzes the ATP-dependent insertion of Co11 into the corrin ring during the biosynthesis of coenzyme B12 in Pseudomonas denitrifleans. Cobaltochelatase is a heterodimeric enzyme (140 KDA and 450 KDA subunits each inactive in isolation), and the two components have been isolated and purified to homogeneity.1119 The reaction product is divalent cobyrinic acid, demonstrating that hydrogenobyrinic acid and its diamide (255) are precursors of AdoCbl. 

A similar type of oxygen complex has been observed during the oxidation of [Con(CN) s]-3 but it was not possible to show that this species was formed in the initial reaction step since with this system, as with the cobaloxime(II) system, the 1 1 adduct apparently reacts very rapidly with another molecule of pentacyanocobaltate(II) to form a diamagnetic binuclear complex with a bridging peroxide ligand 116). It appears that in the Bi2-system the bulk of the corrin ring does not allow formation of the diamagnetic binuclear complex. 

A third factor has been suggested for enhanced resolution of the Co(II) ESR spectrum, because in the enzyme the movement of the acetamide and propionamide side-chains of the corrin ring will be restricted. This restriction would diminish fluctuations in the magnetic environment of the cobalt. 

The application of ESR to the ribonucleotide reductase system indicates that the catalytic intermediate is a Co(I)-species. The appearance of Cob(Il)alamin is probably caused by partial oxidation of the Co(I)-species. In the enzyme bound Co(II)-species the benzimidazole ligand is coordinated, and the corrin ring is bound so tightly that the enzyme produces a unique highly resolved ESR spectrum. 

Use of CD30D or methyl tetrahydrofuran solvents to encourage electron capture, resulted in a complex set of reactions for methyl cobalamine. Initial addition occurred into the w corrin orbital, but on annealing a cobalt centred radical was obtained, the e.s.r. spectrum of which was characteristic of an electron in a d z.y orbital (involving the corrin ring) rather than the expected d2z orbital. However, the final product was the normal Co species formed by loss of methyl. Formally, this requires loss of CH3 , but this step seems highly unlikely. Some form of assisted loss, such as protonation, seems probable. 

A further example concerns the substitution reactions of the co-balamins (vitamin Bi2). Here the usually inert Co(III) center is labi-lized by the corrin ring, which induces a dissociative substitution behavior. A series of detailed studies of the effect of pressure on com-... 

Like many vitamins, cobalamin is functionally active as a derived coenzyme, coenzyme B12. Structurally, this is composed of a corrin ring a haem-like porphyrin ring containing cobalt (Co3+) at the centre held by four coordination bonds. The fifth... 

---