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Co α ‐(1 H ‐Imidazolyl)‐ Co β ‐methylcob(III)amide: Model for Protein‐Bound Corrinoid Cofactors
Author(s) -
Fasching Mario,
Schmidt Wolfgang,
Kräutler Bernhard,
Stupperich Erhard,
Schmidt Andrea,
Kratky Christoph
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000906)83:9<2295::aid-hlca2295>3.0.co;2-t
Subject(s) - chemistry , amide , stereochemistry , corrinoid , crystallography , cofactor , reactivity (psychology) , crystal structure , medicinal chemistry , methylation , organic chemistry , methyltransferase , enzyme , biochemistry , gene , medicine , alternative medicine , pathology
Co α ‐(1 H ‐Imidazol‐1‐yl)‐ Co β ‐methylcob(III)amide ( 4 ) was synthesized by methylation with methyl iodide of (1 H ‐imidazol‐1‐yl)cob(I)amide, obtained by electrochemical reduction of Co α ‐(1 H ‐imidazol‐1‐yl)‐ Co β ‐cyanocob(III)amide ( 5 ). The spectroscopic data and a single‐crystal X‐ray structure analysis indicated 4 to exhibit a base‐on constitution in solution and in the crystal. The crucial lengths of the axial Co−N and Co−CH 3 bonds also emerged from the crystallographic data and were found to be smaller by 0.1 and 0.02 Å, respectively, than those in methylcob(III)alamin ( 2 ). The data of 4 support the view, that the `long' axial Co−N bonds as determined by X‐ray crystallography for the B 12 ‐dependent methionine synthase, for methylmalonyl‐CoA mutase, and for glutamate mutase represent stretched Co−N bonds. The thermodynamic effect (the ` trans influence') of the 1 H ‐imidazole base in 4 on the organometallic reactivity of this model for protein‐bound organometallic B 12 cofactors was examined by studying Me‐group‐transfer equilibria in aqueous solution and using (5′,6′‐dimethyl‐1 H ‐benzimidazol‐1‐yl)cobamides (cobalamins) as reaction partners ( Schemes 2 – 5 , Table ). In comparison with methylcob(III)alamin ( 2 ), 4 was found to be destabilized for an abstraction of the Co‐bound Me group by a Co III electrophile. In contrast, the abstraction of the Co‐bound Me group by a radical(oid) Co II species was not significantly influenced thermodynamically by the exchange of the nucleotide base. Likewise, exploratory Me‐group‐transfer experiments with Me−Co III and nucleophilic Co I corrinoids at pH 6.8 provided an apparent equilibrium constant near unity. However, this finding also was consistent with partial protonation of the imidazolylcob(I)amide at pH 6.8, suggesting an interesting pH dependence of the Megroup‐transfer equilibrium near neutral pH. Therefore, the replacement of the 5′,6′‐dimethyl‐1 H ‐benzimidazole base by an 1 H ‐imidazole moiety, as observed in methyl transferases and in C‐skeleton mutases, does not by itself strongly alter the inherent reactivity of the B 12 cofactors in the crucial homolytic and nucleophilic‐heterolytic reactions involving the organometallic bond, but may help to enhance the control of the organometallic reactivity by protonation/deprotonation of the axial base.