8039-03-0Relevant articles and documents
Coα-(1H-Imidazolyl)-Coβ-methylcob(III)amide: Model for protein-bound corrinoid cofactors
Fasching, Mario,Schmidt, Wolfgang,Kraeutler, Bernhard,Stupperich, Erhard,Schmidt, Andrea,Kratky, Christoph
, p. 2295 - 2316 (2000)
Coα-(1H-Imidazol-1-yl)-Coβ-methylcob(III)amide (4) was synthesized by methylation with methyl iodide of (1H-imidazol-1-yl)cob(I)amide, obtained by electrochemical reduction of Coα-(1H-imidazol-1-yl)-Coβ-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-CH3 bonds also emerged from the crystallographic data and were found to be smaller by 0.1 and 0.02 A, 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 B12-dependent methionine synthase, for methylmalonyl-CoA mutase, and for glutamate mutase represent stretched Co-N bonds. The thermodynamic effect (the 'trans influence') of the 1H-imidazole base in 4 on the organometallic reactivity of this model for protein-bound organometallic B12 cofactors was examined by studying Me-group-transfer equilibria in aqueous solution and using (5',6'-dimethyl-1H-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 Me-group-transfer equilibrium near neutral pH. Therefore, the replacement of the 5',6'-dimethyl-1H-benzimidazole base by an 1H-imidazole moiety, as observed in methyl transferases and in C-skeleton mutases, does not by itself strongly alter the inherent reactivity of the B12 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.
Mechanistic insight from activation parameters for the reaction between co-enzyme B12 and cyanide: Further evidence that heterolytic Co-C bond cleavage is solvent-assisted
Hamza, Mohamed S.A.,Cregan, Andrew G.,Brasch, Nicola E.,Van Eldik, Rudi
, p. 596 - 602 (2003)
The potential involvement of the solvent in heterolytic Co-C bond cleavage for vitamin B12 derivatives has been probed by measuring for the first time activation parameters for heterolytic Co-C bond cleavage. If a water molecule is part of the transition state, negative entropies and volumes of activation should be observed. Conversely, if Co-C bond cleavage is a purely dissociative process, these parameters will be positive. Activation parameters have been determined for the reactions of co-enzyme B12 (5′-deoxyadenosylcobalamin, AdoCbl) and the corresponding cobinamide, 5′-deoxyadenosylcobinamide (AdoCbi+), with cyanide, since previous studies have shown that these reactions proceed at convenient rates, Co-C heterolytic bond cleavage is rate-determining and the reaction proceeds cleanly (that is, negligible homolytic cleavage). In addition, the kinetics of the reaction of AdoCbl with cyanide in aqueous solution were re-investigated at high concentrations of sodium cyanide (up to 3.00 M) at pH 11.0 and I = 5.0 M (NaClO4) using UV-visible and 1H NMR spectroscopy. A significant kinetic saturation was obtained at high CN- concentrations and the limiting rate constant at 25.0°C was found to be (2.21 ± 0.04) × 10-2 s-1, with an overall formation constant for the (β-Ado)(α-CN)Cbl- intermediate, KCN/KCo, of 0.259 ± 0.007 M-1, ΔH≠, ΔS≠ and ΔV≠ under these conditions were found to be 55 ± 1 kJ mol-1, -98 ± 3 J K-1 mol-1 and -5.7 ± 0.3 cm3 mol-1, respectively. ΔV≠ for the reaction of AdoCbi+ and CN- at pH 11.0 and 35.0°C was found to be -4.5 ± 0.4 cm3 mol-1, while ΔV≠ for the reaction of AdoCbl and AdoCbi+ with tetrabutylammonium cyanide in 92% DMF-8% D2O at 35°C was found to be -8.2 ± 0.3 and -8.8 ± 0.7 cm3 mol-1, respectively. The activation parameters data obtained in the present study support the earlier suggestion that the rate determining step for the reaction of AdoCbl and AdoCbi+ with CN- which involves heterolytic cleavage of the Co-C bond of the (β-Ado)(α-CN)Cbl- and (β-Ado)(α-CN)Cbi intermediates, respectively, is a solvent-assisted, β-elimination process, in which the solvent partially protonates the ribosyl oxygen of the intermediate.
A cyclodecapeptide ligand to vitamin B12
Dulery, Vincent,Uhlich, Nicolas A.,Maillard, Noelie,Fluxa, Viviana S.,Garcia, Julian,Dumy, Pascal,Renaudet, Olivier,Reymond, Jean-Louis,Darbre, Tamis
, p. 4134 - 4141 (2008)
Libraries of cyclic decapeptides were screened with vitamin B12 derivatives to give cyclic peptide ligands incorporating histidine and cysteine as coordinating residues and negatively charged amino acids. Two hits, cyclo-(HisAspGluProGlyIleAlaThrProdGln) and cyclo- (ValAspGluProGlyGluAspCysProdGln) were resynthesized in good yields for solution experiments. The peptides bind aquocobalamin with coordination of His or Cys to the cobalt with high affinities (Ka～105 M -1). Additional interactions between the peptide side chains and the vitamin B12 corrin moiety were determined by studying the 1H NMR solution structure. The cyclopeptide-cobalamin complex with the histidine residue showed enhanced stability towards cyanide exchange, demonstrating the shielding effect of the ligand on the metal center.
Mechanistic studies on the interaction of reduced cobalamin (vitamin B12r) with nitroprusside
Wolak, Maria,Stochel, Grazyna,Van Eldik, Rudi
, p. 1334 - 1351 (2003)
The electron-transfer reaction between reduced cobalamin (Cbl(II)) and sodium pentacyanonitrosylferrate(II) (sodium nitroprusside, NP), as well as the subsequent processes following the electrontransfer step, were investigated by spectroscopic (UV-vis, 1H NMR, EPR), electrochemical (CV, DPV) and kinetic (stopped-flow) techniques. In an effort to clarify the complex reaction pattern observed at physiological pH, systematic spectroscopic and kinetic studies were undertaken as a function of pH (1.8-9) and NP concentration (0.0001 - 0.09 M). The kinetics of the electron-transfer reaction was studied under pseudo-first-order conditions with respect to NP. The reaction occurs in two parallel paths of different order, viz. pseudo-first and pseudo-second order with respect to the NP concentration, respectively. The contribution of each path depends on pH and the [NP]/[Cbl(II) ratio. At low pH and total NP concentration (pH I(CN)3 (NO+)]- (1s) is the final reaction product formed in an inner-sphere electron transfer reaction that is coupled to the release of cyanide from coordinated nitroprusside. At higher pH, subsequent reactions were observed which involve the attack of cyanide released in the electron transfer step on the initially formed cyano-bridged species, and lead to the formation of Cbl(III)CN and [FeI(CN)4(NO+)]2-. The strong dependence of the rate and mechanism of the subsequent reactions on pH is attributed to the large variation in the effective nucleophilicity of the cyanide ligand in the studied pH range. An alternative electron-transfer pathway observed in the presence of excess NP involves the reaction of the precursor complex [Cbl(II)-(μ-NC)-FeII(CN)4 (NO+)]2- (1p) with NP to give [Cbl(III)-(μ-NC)-FeII(CN)4 (NO+)- (2) and reduced nitroprusside, [Fe(CN)5NO]3-, as the initial reaction products. Analysis of the kinetic data allowed elucidation of the rate constants for the inner- and outer-sphere electron-transfer pathways. The main factors which influence the kinetics and thermodynamics of the observed electron-transfer steps are discussed on the basis of the spectroscopic, kinetic and electrochemical results. A general picture of the reaction pathways that occur on a short (s) and long (min to h) time scale as a function of pH and relative reactant concentrations is derived from the experimental data. In addition, the release of NO resulting from the one-electron reduction of NP by Cbl(II) was monitored with the use of a sensitive NO electrode. The results obtained in the present study are discussed in reference to the possible influence of cobalamin on the pharmacological action of nitroprusside.
Identification of diastereomeric cyano - Aqua cobinamides with a backbone-modified vitamin B12 derivative and with 1H NMR spectroscopy
Zhou, Kai,Zelder, Felix
, p. 53 - 57 (2011)
A new backbone-modified vitamin B12 derivative with an unusual configuration at the cobalt center has been used for the identification of the two axial diastereomers of cyano-aqua cobinamides (Cbi) by using 1H NMR spectroscopy. A new backbone-modified vitamin B12 derivative with an unusual configuration at the cobalt center has been used for theidentification of the two axial diastereomers of cyano-aqua cobinamides (Cbi) by using 1H-NMR spectroscopy. Copyright
