Probing the Nature of the Co^IIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B_12a) with Ambident Nucleophiles

Abstract

The rate of substitution of the H2O β‐ligand in aquacobalamin (vitamin B12a) is surprisingly fast for CoIII. This may arise as a result of transfer of electron density to CoIII by the corrin, conferring on the metal atom a softer and more labile character, and would require electronic communication between the equatorial ligand and the axial coordination sites of the metal atom. We have substituted H2O in B12a with the ambidentate nucleophiles SCN−, SeCN−, NO2− and S2O32−, examined the UV/Vis spectra of the resultant complexes, crystallised them, and determined their structures by X‐ray diffraction methods. The UV/Vis spectra of these complexes, as well as those of H2OCbl+, SO3Cbl− and MeCbl, were fitted by Gaussian functions. The principal bands move to lower energy in response to an increase in donation of electron density from the axial ligand, demonstrating direct electronic communication between the axial and the equatorial ligands. In the solid state, the thiocyanato ligand in SCNCbl is coordinated through N, although 13C NMR spectroscopy shows that the complex exists as a mixture of two linkage isomers in solution. SeCN−, NO2− and S2O32− are coordinated through the softer available donor in each case (Se, N and S, respectively). There is a regular ground‐state trans effect such that as the donor power of the β‐ligand increases, the trans Co−Nax bond length increases. A survey of the structures available in the CSD shows that this preference for the softer donor atom in ambidentate nucleophiles is not unusual in CoIII complexes. The Co−N bond length in SCNCbl is marginally long for coordination to CoIII, but the axial bond lengths of the other complexes are as expected. Hence, whereas the corrin macrocycle clearly imparts lability on CoIII, presumably by transfer of electron density onto the metal atom, this is insufficient to have a major effect on the ground‐state structures of its complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Probing the nature of the Co(III) ion in cobalamins: The reactions of aquacobalamin (vitamin B12a), aqua-10-chlorocobalamin and aqua-10-bromocobalamin with anionic and neutral ligands

“…The Co-N21 and Co-N23 bond lengths are longer in [N 3 -(10-Br)Cbl] than in [N 3 Cbl] whereas the Co-N22 and Co-N24 bonds are shorter; hence the corrin cavity has undergone a distortion with the N21Á Á ÁN23 distance increasing but the N22Á Á ÁN24 distance decreasing when C-10 H is substituted by Br. The 10-Br derivative is also marginally more folded (the corrin fold angle in [N 3 -(10-Br)Cbl] is 18.5°but 16.3°in N 3 Cbl).…”

“…Since the hydroxo complex [HO-(10-Br)Cbl], by analogy with [HOCbl], is expected to be substitution inert [20,21], and the conjugate acids HN 3 and HIm + are unlikely to coordinate Co(III), k I obs was converted to a pH-independent first order rate constant, k I by applying the equivalent of Eq. (5).…”

“…We have been exploring the nature of Co(III) in the cobalt corrins (derivatives of vitamin B 12 ) in an effort to elucidate the effect of the corrin ligand on the chemistry of the metal ion [1][2][3][4][5][6][7][8][9][10][11][12]. We have suggested that an important factor in modifying the properties of normally inert Co(III) and conferring on it the unusual lability found in the cobalt corrins is the delocalisation of electron density from the corrin equatorial ligand onto Co(III), making the metal softer and imparting on it some measure of labile Co(II) character.…”

A simple, convenient method to synthesize cobalamins: synthesis of homocysteinylcobalamin, N-acetylcysteinylcobalamin, 2-N-acetylamino-2-carbomethoxyethanethiolatocobalamin, sulfitocobalamin and nitrocobalamin

“…Although both are isolable from biological samples, [11][12][13][14][15][16][17]20 and are well studied and structurally characterized, 23,29,38,43,[59][60][61][62][63][64][65][66][67][68][69] neither are commercially available. NO 2 Cbl is also of interest, since if nitrosylcobalamin (NOCbl) is formed in biological systems to any appreciable extent, NO 2 Cbl rather than NOCbl will be isolated after typical (aerobic) isolation and purification procedures.…”

Cob(I)alamin reacts with sucralose to afford an alkylcobalamin: Relevance to in vivo cobalamin and sucralose interaction

“…Upon irradiation of the Suc-Cbl in methanol with visible light under aerobic conditions we obtained aquocobalamin (H 2 O-Cbl) (Fig. 3 B) with its prominent band at 360 nm implying homolytic cleavage of the Co-C σ bond (Firth et al, 1967;Perry et al, 2003;Schrauzer et al, 1970). Such type of cleavage mechanism by homolysis is similar to that of the Co-C bond on adenosylcobalamin-dependent isomerases generating a protein bound free radical, 5'-deoxyadenosyl, that catalyze a 1,2 interchange between a variable substituent and a hydrogen atom on vicinal carbons (Banerjee, 1999;Banerjee et al, 2003;Golding et al, 1997).…”