Acid‐induced decomposition of coenzyme B₁₂ and variants

Abstract

The acid‐catalyzed heterolytic cleavage of the Co‐C bond in coenzyme B12 (1) and adocobinamide hydroxide (2) was studied using the excess‐acidity functions of Cox and Yates. The results are compared to the acid‐induced decomposition of methyl(5′‐deoxyribofuranosyl)cobalamin (3) and (2‐ethoxyethyl)cobalamin (4). Evidence is presented to view the bond cleavage in the compounds 1, 2 and 3 as an A2 mechanism or as an Ia substitution at Co3+, with water as the nucleophile, and in 4 as an A1 mechanism. For 1, the temperature dependence (289‐320 K) gives ΔS‡ = − 96 J/(K· mol), in agreement with the Ia (A2) mechanism. For the A2 reactions the volumes of activation [ΔV‡ = −11.4 (1), −8.2 (2) and −11.5 (3) cm3/mol in 2‐4M acid at 298K] are consistent with the proposed mechanism, but ΔV‡ for the A1 mechanism of 4 is exceptionally negative (‐7.2 cm3 /mol), probably due to intramolecular coordination in the transition state. A comparison with the much slower acid‐induced decomposition of 5′‐deoxyadenosine brings out the labilization of the furanosyl oxygen bridge by coordination of the 5′‐deoxyadenosyl or 5′‐deoxyribofuranosyl group at the β‐position to cobalt. For 5′‐deoxyadenosine the excess‐acidity treatment and the activation volume (ΔV‡ = 1.7 cm3/mol in 2 M acid) indicate a clear A1 mechanism.

Determination of four forms of vitamin B12 and other B vitamins in seawater by liquid chromatography/tandem mass spectrometry

“…The published stable pH range for all analyzed cobalamins is pH 4–7, with lower pHs resulting in lower retention on a C18 SPE and acid‐induced heterolysis of Ado‐Cbl . Me‐Cbl and Ado‐Cbl are particularly labile, so we focused on decreasing processing time (from 66 to 8 h for the preconcentration step) and eliminating the 2 nd SPE (pH 2) step required in previously published methods .…”

The enzymatic activation of coenzyme B12

“…3,34 As is the case for all organocobalt compounds with b oxygen substituents, 3 AdoCbl is acid labile, and undergoes a heterolytic process which yields aquacobalamin (H 2 OCbl + ), adenine, and 2,3-dihydroxy-4-pentenal, in a process that is both specific acid-catalyzed and general acid (solvent) catalyzed. 3,34,75, 76 The competing process is carbon-cobalt bond homolysis, which is known to proceed through a solvent-caged cob(II)alamin-Ado • radical pair and consequently to be diffusion controlled in solution. 34,51,77,78, 79 The fate of the caged radical pair varies with conditions.…”

Dealkylation of Coenzyme B12 and Related Organocobalamins: Ligand Structural Effects on Rates and Mechanisms of Hydrolysis

“…A striking feature of the organometallic chemistry of coenzyme B 12 is the minimization of nonproductive side reactions, for example β-hydride or β-alkoxide − eliminations that would cleave the Co−C bond irreversibly (Scheme ). The latter pathway was observed in early studies aimed at elucidation of the structure of Ado-B 12 , which indicated that cyanide was replaced on vitamin B 12 by a nucleoside that released 1 equiv.…”