Thermodynamic trans‐Effects of the Nucleotide Base in the B₁₂ Coenzymes

Abstract

The thermodynamic effects of the nucleotide coordination on the Co‐C bond strengths in the B12 coenzymes were analyzed. Methyl group transfer reactions from methylcob(III)inamides to cob(II)inamides and cob(I)inamides in neutral aqueous solution were used in equilibration experiments to determine the effect fo the intramolecular coordination of the nucleotide function on the Co‐C bond dissociation energies of methylcob(III)alamin (4). In the equilibrium between 4, cob(I)inamide (11), cob(I)alamin (10) and methylcob(III)inamide 6 (Scheme 2), 4 and 11 were found to predominate (4+11⇆10+6, equilibrium constant KI/III≈0.004), while the equilibrium between 4, cob(II)inamide 9, cob(II)alamin (5), and 6 (Scheme 1) proved to be well balanced (4+9⇄5+6, equilibrium constant KII/III=0.60). These equilibrium values indicate the nucleotide coordination to stabilize the Co–C bond in 4 both against homolysis (slight effect) and against nucleophilic heterolysis (considerable effect). They reflect a stabilization of the complete corrins 4 and 5by the nucleotide coordination, which is also indicated for 4 and 5 by their (nucleotide) basicity. The latter information, where available for other organocobalamins, allows the analysis of the thermodynamicnucleotide trans effect there as well: e.g. in coenzyme B12 (1), the nucleotide coordination is found this way to weaken the Co–C bond towards homolysis by ca. 0.7 kcal/mol.

Spectroscopic Studies of the Corrinoid/Iron−Sulfur Protein from Moorella thermoacetica

“…16,18 Numerous thermodynamic studies of alkylated corrinoid model complexes have shown that the nature of the lower ligand has a considerable influence on both the mode (i.e., homolytic vs heterolytic) and the rate of Co-C bond cleavage. [19][20][21][22][23] Consequently, the lower axial ligand is expected to play a key role in controlling both the reaction of Co 1+ CFeSP with CH 3 -H 4 folate and the transfer of the methyl cation from Me-Co 3+ CFeSP to the ACS A-cluster, and it is therefore of considerable interest to unambiguously establish the binding scheme of the corrinoid cofactor in CFeSP. To this end, we have employed our recently developed combined spectroscopic and computational methodology [24][25][26][27] to probe the electronic structures, and thus indirectly the axial ligand interactions, of the methylated and Co 2+ -containing forms of Factor III m in the CFeSP active site.…”

Methylcorrinoids Methylate Radicals—Their Second Biological Mode of Action?

“…are known. [18,19] The occurrence of related intramolecular mechanisms was suggested to be responsible for the formation of (substituted) cycloalkanes from organometallic, bridged B 12 dimers, [20] as well as from hexenyl cobaloximes. [18] Homolytic substitution reactions at carbon centers, when examined more closely, were found to take place with stereochemical inversion of configuration.…”

“…[18] Homolytic substitution reactions at carbon centers, when examined more closely, were found to take place with stereochemical inversion of configuration. [17,18] As a result of its characteristical low homolytic (Co-C)-BDE [12] 1 has the reactivity of a ªlatentº (persistent) methyl radical towards radicals [19,21] and, similar to coenzyme B 12 (8, a ªreversibly functioning source of an alkyl radicalº), [23] should be considered a partner in biological radical reactions. The enzymatic transfer of a methyl group from 1 to a carboncentered radical should proceed with inversion of the configuration of the methyl group (and should therefore occur with net retention of configuration from methionine).…”

5′‐Methylbenzimidazolyl‐cobamides are the corrinoids from some sulfate‐reducing and sulfur‐metabolizing bacteria

“…First, possible effects of the nucleotide structure on the reactivities of these corrins should be considered that are relevant for their biological role. The coordination of the nucleotide base at the a-face of the corrin-bound cobalt center (a) has been suggested to direct the radical-alkylation reactions to the (usual) p-face of the corrin-bound cobalt ion [44, 451 and (b) has been shown to modify the strength of the organometallic bond (on the p-face) in methyl-corrins [45,46] and other organocorrins [47] in aqueous solution, as well as their one-electron redox properties [46, 481. In methyl group equilibration experiments between corrinoids in neutral aqueous solution the nucleotide coordination in methylcobalamin (2) (compared to the coordination of water in an incomplete corrin) was found to stabilize the Co-C bond by about 17.5 kJ/ mol against heterolytic nucleophilic cleavage and by about 1.2 kJ/mol against homolytic cleavage [46]. In corresponding exploratory methyl transfer experiments between 5',6'-dimethylbenzimidazolylcobamides and 5'-hydroxybenzimidazolylcobamides only a slight effect of the differing base was observed on the homolysis of the Co-CH3-bond (favouring 2 by < 0.8 kJ/mol over the Cop:methyl form of 4) [45].…”