ACID-INDUCED DECOMPOSITION OF COENZYME-B(12) AND VARIANTS

The acid-catalyzed heterolytic cleavage of the Co-C bond in coenzyme B -12 (1) and adocobinamide hydroxide (2) was studied using the excess-a cidity functions of Cox and Yates. The results are compared to the aci d-induced decomposition of methyl(5'-deoxyribofuranosyl)cobalamin (3) and (2-ethoxyethyl)cobalamin (4). Evidence is presented to view the bo nd cleavage in the compounds 1, 2 and 3 as an A2 mechanism or as an I( a) substitution at Co3+, with water as the nucleophile, and in 4 as an Al mechanism. For 1, the temperature dependence (289-320 K) gives DEL TAS(double dagger) = - 96 J/(K.mol), in agreement with the I(a) (A2) m echanism. For the A2 reactions the volumes of activation [DELTAV(doubl e dagger) = - 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 DELTAV(double dagger) for the Al mechanism of 4 is exceptionally negative (-7.2 cm3 /mol), probably due to intramolecular coordination in the transition s tate. 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'-deoxyribofuranosy l group at the beta-position to cobalt. For 5'-deoxyadenosine the exce ss-acidity treatment and the activation volume (DELTAV(double dagger) = 1.7 cm3/mol in 2 M acid) indicate a clear A1 mechanism.