Corrins biology

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. 

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... 

The most exciting research is yet to be performed on 13C NMR of the corrin enzymes. This could be accomplished by biosynthesis of C-13 enriched samples of biologically active B12 derivatives followed by their incorporation into enzymes. Since it has been shown that 13C-spectra of corrinoids are well resolved, and sensitive to small changes in the molecular conformation, then one could hope to get quite detailed information pertinent to the binding of B12 and to the mechnism of enzyme catalysis. 

As a class, metal-ion derivatives of tetrapyrrole macrocyclic rings, such as the corrins or porphyrins (see Chapter 1 for the parent ring structures), are of major biological importance. 

Let me put it to Professor Lehn that biology can do better than he can with small molecules. From uroporphyrin biology makes (1) copper porphyrins (turacin feathers), (2) heme (iron) porphyrins, (3) magnesium chlorins, (4) cobalt corrins (B12). These compounds are formed with very little confusion between metals and partners. I cannot give selectivity factors, but they are very big. How is this managed Is it not better than man can do Maximum size selectivity for anions is not yet understood as few anion-binding sites in biology are known. 

Porphyrins and corrins form part of the prosthetic groups in a large variety of vitally important natural products. As a result of intense interest in the structure, function and mechanistic details of the biological systems containing porphyrins and chlorins, the whole field has developed in a most remarkable way over the past 50 or more years. There can be few other research areas which possess such a rich, eventful and informative historical literature, and yet continue to produce important and exciting revelations in current journals. 

The structures of the biologically active forms of B12 were solved relatively recently (1961) (78) and were shown to contain a cobalt atom surrounded by a corrin ring as shown in Fig. 16 (80). The crystal structure also showed a cobalt-carbon a bond which was quite surprising since the few compounds with cobalt-carbon a- bonds known at that time were quite unstable (79). The corrin ring is similar to the porphyrin ring, but its greater saturation imports less rigidity than the porphyrin. Corrinoids with the axial 5,6-dimethylbenzimidazole substituent are called cobalamins. Vitamin B12 with Co(III) and CN in the top axial position is... 

Biologically essential tetrapyrrolic macrocycles of two main types exist the porphyrins, the prosthetic group of heme proteins, and the corrins, most representative among which is the coenzyme of Vitamin B12. 

Most research involving the NMR of corrins has been performed with vitamin B12 and its biologically active intermediates. The purpose of many such studies... 

Eschenmoser conceived a synthesis of corrins which could be extended to biological compounds. In this method a Cd2+ complex of the secocorrin which formula is shown in Fig. 24a (R = =CH2, R = H, R" = CN) is converted... 

The substituents present at the 20 position are characteristic of this structure the methyl group is present in Factor III, an intermediate in the biological conversion of uroporphyrinogen to Vitamin B12- The hydroxyl group represents the hypothetical subsequent biological transformation. Their presence is essential for ring contraction in the absence of the 20-methyl group the conversion to the corrin skeleton does not occur, but there is tautomerizaton to a keto form [69, 79-81],... 

The use of metal ions as templates for macrocycle synthesis has an obvious relevance to the understanding of how biological molecules are formed in vivo. The early synthesis of phthalocyanins from phthalonitrile in the presence of metal salts (89) has been followed by the use of Cu(II) salts as templates in the synthesis of copper complexes of etioporphyrin-I (32), tetraethoxycarbonylporphyrin (26), etioporphyrin-II (78), and coproporphyrin-II (81). Metal ions have also been used as templates in the synthesis of corrins, e.g., nickel and cobalt ions in the synthesis of tetradehydrocorrin complexes (64) and nickel ions to hold the two halves of a corrin ring system while cycliza-tion was effected (51), and other biological molecules (67, 76, 77). 

The iron porphyrins and related compounds constitute an extremely important class of coordination complex due to their chemical behaviour and involvement in a number of vital biological systems. Over recent years a vast amount of work on them has been published. Chapter 21.1 deals with the general coordination chemistry of metal porphyrins, hydroporphyrins, azaporphyrins, phthalocyanines, corroles, and corrins. Low oxidation state iron porphyrin complexes are discussed in Section 44.1.4.5 and those containing nitric oxide in Section 44.1.4.7, while a later section in this chapter (44.2.9.2) is mainly concerned with iron(III) and higher oxidation state porphyrin complexes. Inevitably however, a considerable amount of information on iron(II) complexes is contained in that section as well as in Chapter 21.1. Therefore in order to prevent excessive duplication, the present section is restricted to highlighting some of the more important aspects of the coordination chemistry of the iron(II) porphyrins while the related unusually stable phthalocyanine complexes are discussed in the previous section. 

As shown in Figure 10.12, four of the six chelation sites of the cobalt atom of cobalamin are occupied by the nitrogens of the corrin ring and one by the nitrogen of the dimethylbenzimidazole side chain. The sixth site may be occupied by the following ligands in biologically active vitamers ... 

The biologically relevant reactivity of coenzyme B12 is associated with the homolysis of its Co-C bond, as well as with the recombination of the products of homolysis (Figure 8). The remarkable structural similarity between the corrinoid homolysis fragment Co"-cobalamin and the Co "-corrin part of coenzyme B12 contributes to lowering... 

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