Corrins nucleophilicity

Coproporphyrin I synthesis, 816 Coronands classification, 919 metal ion complexes, 928,938 Corphins, 855 Coninoids, 983 Corrins, 871-888 demetallation, 882 deuteration, 879 electrophilic reactions, 879 metallation, 882 NMR, 878 nucleophilicity, 886 nucleophilic reactions, 879 oxidation, 879 oxidative lactamization, 880 oxidative lactonization, 880 photochemistry, 887 reactions, 879 at metal, 885 rearrangements, 879 redox chemistry, 888 spectra, 877 synthesis, 878 Corroles, 871-888 demetallation, 874 deuteration, 872 hydrogenation, 872 metallation, 874 reactions, 872 at metal, 875 redox chemistry, 876 synthesis, 871 Corticotropin zinc complexes medical use, 966 Cotton effect anils, 717... 

It has been suggested that interaction of the dmbim pulls the Co into the corrin plane, sterically inhibiting nucleophilic displacement at the axial methyl [166]. A bound imidazole would play the same role. Therefore, release of this steric strain in base-off Cbls and in MeCbi+ should facilitate dealkylation base-off species dealkylate more rapidly [166], but different products are observed. It is essential to assess the relative importance of steric and electronic effects on... 

The N-oxides of special position, although their reactions with nucleophilic reagents are similar to the reactions of other imines. These compounds have been studied particularly in connection with attempts to synthesize the cyclic skeleton corrin of vitamin B12. 

Two major mechanisms have to be taken into consideration for the alkylation of Co -corrins. The classical mechanism of a bimolecular nucleophilic substitution reaction at carbon (the Co -corrin acts as a nucleophile) leads to /3-aUcylated Co -corrins with high diastereoselectivity. Secondly, an electron transfer-induced radical process (where the Co -corrin acts as a one-electron reducing agent) may also lead to cobalt alkylation. The observed formation of incomplete a-aUcylated Co -corrins under kinetically controlled conditions has been proposed to occur via this path. The high nucleophilic reactivity of Co -corrins and their diastereoselective nucleophilic reaction on the ( upper ) /3-face are not increased by the nucleotide function on the ( lower ) a-face rather they appear to be an inherent reactivity of the corrin-bound tetracoordinate Co -center. Among the organometallic B12 derivatives prepared to date, neopentylcobalamin, benzylcobalamin, and... 

The cobalt-bound methyl group of (4) is not readily removed by acid. Treatment of (4) with acid in aqueous solution leads to proteolytic decoordination of the nucleotide base (pXa = 2.9). The cobalt-bound methyl group of methyl-Co "-corrins can be abstracted (1) by nucleophiles, such as thiol(ate)s, " > " (2) by radicaloid species, such as other Co"-corrins, or (3) by electrophilic species, such as Hg"-ions. A reversible and rapid methyl-group transfer occurs in deoxygenated aqueous solution between methyl-Co "-corrins and Co -corrins. From the pair, methyl-Co "-cobinamide and Co -cobalamin (6), methylcobalamin (4) and Co -cobinamide are generated and prevail at equilibrium. 

The cobalt(I) species that is generated is a very powerful nucleophile and a highly unstable entity. It is required as a substrate for the adenosyltransferase, which adds the upper adenosyl ligand to the centrally chelated cobalt ion. The enzyme responsible for this process is encoded by cobO The enzyme catalyzes the adenosyl transfer from ATP to a range of corrins, including cob(I)yrinic tf,c-diamide, cob(I)yrinic acid, and cob(I)inamide, generating the cobalt(III) corrinoid and triphosphate. The P. denitriftcans CobO is a homodimer with a... 

Soft nucleophiles (X = CN , SCN , 1 ) attack Ni(5-C1CH2- or 5-HOCH2-ODC) at C-10 to give Ni(5-Me-10-X-ODC), white 5 2 reactions occur with hard nucleophiles (HO , CF3C02 ). Oxidation of natural cobalt(III) corrins by KMuO -pyridine gives 5- or 15-carboxy and 5,I5-di-carboxy derivatives. Acetoxylation of the meso methyl groups has also been reported. ... 

Due to the discovery of the replacement of the cobalt coordinated 5,6-dimethylimidazole (DMB) base by a protein-derived imidazole in several Bi2-dependent enzymes (see later), the analysis of Co -cyano-imidazolylcob-amide (8) [31] was of particular interest. The less bulky and more nucleophilic imidazole base of 8 caused a number of structural differences. The corrin ring fold angle of 8 decreased to 11.3° and the axial Co-N bond shortened (from 2.011 A in 1 to 1.968 A in 8). In addition, the base tilt of 8 (i.e., half the difference between the two Co - N - C angles to the coordinating base) decreased to practically zero, within experimental error. In all crystal structures of 5, 6 -dimethylbenzimidazoyl-cobamides a tilt of about 5° is found [36], which appears to be an inherent property of the cobalt-coordinated DMB. 

Co -methyl-imidazolylcobamide (31) was prepared as a model for organo-metallic Bn-cofactors in a base-off/His-on form and its crystal structure was analyzed [68]. The substitution by a less bulky and more nucleophilic imidazole base had the expected structural effects. The axial Co - C (1.97 A) and Co-N (2.09 A) are shorter in 31 than in methylcobalamin and the fold angle of the corrin Ugand was reduced by over 2° to 12.5°. 

Intramolecular coordination of the nucleotide base or strong coordinating or nucleophilic ligands (such as cyanide ions) stabilize the corrin-bound cobalt center against one-electron reduction and shift the Co(III)-/Co(II)-redox couples to more negative potentials. 

The nucleophile induced, heterolytic mode, is formally a two-electron reduction/oxidation of the corrin-bound cobalt center and involves the cleavage or formation of two (trans-) axial bonds, as is typical of the reactivity of methylcobalamin [ 124-127) ... 

The second important type of organometallic reactivity of B 12-derivatives concerns the highly nucleophilic/nucleofugal Co(I)-corrins [75,91,132[. These provide the basis of the heterolytic mode of formation/cleavage of the Co - C bond, important in methyl-corrinoids in enzyme-catalyzed methyl-transfer reactions [125-127]. This mode is represented by the reaction of Co(I)-corrins with alkylating agents in the formation of the Co - CH3 bond and the nucleophile-induced demethylation of methyl Co(III)-corrins for the... 

The nucleophilicity of Co(I)-corrins is virtually independent of the presence of the DMB-nucleotide, both complete and incomplete Co(I)-corrins react preferentially at their j0-face, which is essentially more nucleophilic [ 132,134]. The immediate product of the /3-alkylation may be a pen-taco ordinate (or already solvated and effectively hexacoordinate) Cop-alkyl-Co(III)-corrin. 

The reverse process, the nucleophile-induced dealkylations of methyl-Co(III)-corrins, has been less studied due to the impediment of the intramolecular coordination of the nucleotide base [134,137]. Indeed, thiolates demethylate methylcobinamide (45) to cob(l)inamide (43) approximately 1000 times faster than MeCbl (3) to B s (40") [137], reflecting the strong stabilizing effect of the coordinated nucleotide in 3 [86,134]. This is of relevance for enzymatic methyl group transfer reactions involving protein bound Co(l)- and methyl-Co(lll)-corrins, where considerable axial base effects are expected [125,138]. 

In the heterolytic mode of cleavage and formation of the Co - C bond significant reorganization at both faces of the corrin-bound cobalt center. Cleavage of the Co - CH3 bond is brought about by attack of a nucleophile at the readily accessible carbon of the cobalt-bound methyl group. 

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