Acid-induced decomposition of coenzyme B12 and variants

✍ Scribed by L.E.H. Gerards; S. Balt

• Book ID: 104589619
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 777 KB
• Volume: 113
• Category: Article
• ISSN: 0165-0513
• DOI: 10.1002/recl.19941130303

✦ Synopsis

Abstract

The acid‐catalyzed heterolytic cleavage of the Co‐C bond in coenzyme B~12~ (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 A~2~ mechanism or as an I~a~ substitution at Co^3+^, with water as the nucleophile, and in 4 as an A~1~ mechanism. For 1, the temperature dependence (289‐320 K) gives Δ__S__‡ = − 96 J/(K· mol), in agreement with the I~a~ (A~2~) mechanism. For the A~2~ reactions the volumes of activation [Δ__V__‡ = −11.4 (1), −8.2 (2) and −11.5 (3) cm^3^/mol in 2‐4M acid at 298K] are consistent with the proposed mechanism, but Δ__V__‡ for the A~1~ mechanism of 4 is exceptionally negative (‐7.2 cm^3^ /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 (Δ__V__‡ = 1.7 cm^3^/mol in 2 M acid) indicate a clear A~1~ mechanism.