Cobalamin reduction

Upon oxidation or reduction, an electroactive species may be activated toward bond cleavage, as in the case of methycobalamin reduction (Figure 2-13). The addition of an electron activates the molecule toward dissociation of a methyl radical. The rate constant of the following reaction is 600s" at — 30°C in a DMF/propanol solvent mixture. The cathodic transfer coefficient a for methyl-cobalamin reduction is 0.78. At even lower temperatures, the anodic peak grows in as a result of the lowering of the dissociation rate. 

Only a few other cobalt complexes of the type covered in this review (and therefore excluding, for example, the cobalt carbonyls) have been reported to act as catalysts for homogeneous hydrogenation. The complex Co(DMG)2 will catalyze the hydrogenation of benzil (PhCOCOPh) to benzoin (PhCHOHCOPh). When this reaction is carried out in the presence of quinine, the product shows optical activity. The degree of optical purity varies with the nature of the solvent and reaches a maximum of 61.5% in benzene. It was concluded that asymmetric synthesis occurred via the formation of an organocobalt complex in which quinine was coordinated in the trans position (133). Both Co(DMG)2 and cobalamin-cobalt(II) in methanol will catalyze the following reductive methylations ... 

Ribonucleotide reductase differs from the other 5 -deoxyadenosyl-cobalamin requiring enzymes in a number of respects. Hydrogen is transferred from coenzyme to the C2-position of the ribose moiety without inversion of configuration. Also since lipoic acid functions in hydrogen transfer, exchange with solvent protons takes place. Furthermore, exchange between free and bound 5 -deoxyadenosylcobalamin occurs rapidly during catalysis. Evidence for a Co(I)-corrin as an intermediate for this reduction is presented in our section on electron spin resonance. 

There is some evidence that the iron-sulfur protein, FhuF, participates in the mobilization of iron from hydroxamate siderophores in E. coli (Muller et ah, 1998 Hantke, K. unpublished observations). However, a reductase activity of FhuF has not been demonstrated. Many siderophore-iron reductases have been shown to be active in vitro and some have been purified. The characterization of these reductases has revealed them to be flavin reductases which obtain the electrons for flavin reduction from NAD(P)H, and whose main functions are in areas other than reduction of ferric iron (e.g. flavin reductase Fre, sulfite reductase). To date, no specialized siderophore-iron reductases have been identified. It has been suggested that the reduced flavins from flavin oxidoreductases are the electron donors for ferric iron reduction (Fontecave et ah, 1994). Recently it has been shown, after a fruitless search for a reducing enzyme, that reduction of Co3+ in cobalamin is achieved by reduced flavin. Also in this case it was suggested that cobalamins and corrinoids are reduced in vivo by flavins which may be generated by the flavin... 

In the field of the reductive (bio)transformation of priority pollutants, the reported redox mediator molecules include cytochromes, pyridines, cobalamins, porphyrins, phenazines, flavines, and quinines [12-15]. However, Quinones have been studied as the most appropriate RM for the reductive (bio)transformation of azo dyes [12]. 

The NO/NO+ and NO/NO- self-exchange rates are quite slow (42). Therefore, the kinetics of nitric oxide electron transfer reactions are strongly affected by transition metal complexes, particularly by those that are labile and redox active which can serve to promote these reactions. Although iron is the most important metal target for nitric oxide in mammalian biology, other metal centers might also react with NO. For example, both cobalt (in the form of cobalamin) (43,44) and copper (in the form of different types of copper proteins) (45) have been identified as potential NO targets. In addition, a substantial fraction of the bacterial nitrite reductases (which catalyze reduction of NO2 to NO) are copper enzymes (46). The interactions of NO with such metal centers continue to be rich for further exploration. 

Successive removed of ligands upon reduction, starting from cobalt(III) aquo-cobalamin ... 

Two-Step Chemical Catalysis of the Reduction of Alkyl Halides by Low-Valent Cobalamins and Cobinamides... 

The role of methylene blue as an inhibitor of the reduction of hydroxy-cobalamins by CO has been studied. 

In animal metabolism, derivatives of cobalamine are mainly involved in rearrangement reactions. For example, they act as coenzymes in the conversion of methylmalonyl-CoA to succinyl-CoA (see p. 166), and in the formation of methionine from homocysteine (see p. 418). In prokaryotes, cobalamine derivatives also play a part in the reduction of ribonucleotides. 

Cobalt complexes with square planar tetradentate ligands, including salen, cor-rin, and porphyrin types, all catalyse the reduction of alkyl bromides and iodides. Most preparative and mechanistic work with these reactions has used cobalamines, including vitamin-B,. A generalised catalytic cycle is depicted in Scheme 4.10 [219]. At potentials around -0.9 V vs. see, the parent ligated Co(lll) compound un-... 

Scheme 4.10. Calalyttc cycle for the reduction of alkyl halides by cobalamins. The outer circle represents the combined photo and electrochemical process, "fhe inner shunt is the wholly electrochemical process at more negative potentials. Ligands are omitted for clarity.

Cobalamin catalysed reduction of alkyl halides has found use in organic synthesis because, like square planar Ni(o), it allows formation of alkyl radicals in the bulk of the solution away from the electi ode surface. Alkyl radical addition to activated alkenes is achieved in high yields. In the cases of primary alkyl halides,... 

Cobalamin catalysed electrochemical reduction of the 2-chloroethanol ester 68 at negative potentials, without photochemical assistance, leads to a 1,2-elimination process (see p. 115) [228]. This contrasts with the lack of 1,2-elimination during reaction of 66 and 67, Thus in the purely electrochemical carbon-cobalt bond... 

The loss of a methyl group from AdoMet in each of the reactions yields S-ad-enosylhomocysteine (AdoHcy) and this is subsequently hydrolysed to adenosine and Hey by AdoHcy-hydrolase. Hey sits at a metabolic branch point and can be remethylated to methionine by way of two reactions. One is the 5-methyltetrahydrofo-late dependent reaction catalysed by methionine synthase, which itself is reductively methylated by cobalamin (vitamin B12) and AdoMet, requiring methionine synthase reductase. 5-Methyltetrahydrofolate is generated from 5,10-methylenetetrahydrofo-late (MTHF) by MTHF reductase. The second remethylation reaction is catalysed by betaine methyltransferase, which is restricted to the liver, kidney and brain, while methionine synthase is widely distributed. 

Glod, G., U. Brodmann, W. Angst, C. Holliger, and R. P. Schwarzenbach, Cobalamin-mediated reduction of cis- and trans-dichlorethene, 1,1-dichloroethene, and vinyl chloride in homogeneous aqueous solution Reaction kinetics and mechanistic considerations , Environ. Sci. Technol., 31, 3154-3160 (1997b). 

Assaf-Anid, N., Hayes, K. F. Vogel, T. M. (1994). Reductive dechlorination of carbon tetrachloride by cobalamin(II) in the presence of dithiothreitol mechanistic study, effect of redox potential and pH. Environmental Science Technology, 28, 246-52. Ballard, T. M. (1971). Role of humic carrier substance in DDT movement through forest soil. Soil Science Society of America Proceedings, 35, 145-7. 

Three types of enzymatic reactions depend upon alkyl corrin coenzymes. The first is the reduction of ribonucleotide triphosphates by cobalamin-dependent ribonucleotide reductase, a process involving intermo-lecular hydrogen transfer (Eq. 16-21). The second type of reaction encompasses the series of isomerizations shown in Table 16-1. These can all be depicted as in Eq. 16-34. Some group X, which may be attached by a C-C, C-O, or C-N bond, is transferred to an adjacent carbon atom bearing a hydrogen. At the same time,... 

The exact role of the nickel of F430 in methane formation is not clear at present. Analogy with the cobalamins, and the observation of an EPR-detectable reduced state, might suggest that it is involved in either methyl group transfer, reduction, or both. 

The reduction properties of the cobalamins also differ from the normal Co111 complexes in that they can be readily reduced to the Co1 state, e.g. as in the methylation reaction (9). The electrochemical properties of the cobalamins have recently been reviewed.151 Several reviews are also available concerning their biological activity, the mechanisms of reactions, and synthetic analogues.150,152-155... 

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