Methylcobalamin's full- vs. "half"-strength cobalt-carbon sigma bonds and bond dissociation enthalpies: A >10(15) Co-CH3 homolysis rate enhancement following one-antibonding-electron reduction of methlycobalamin.

Methylcobalamin (MeCbl, MeB12) thermolyzed in ethylene glycol from 120 to 141 degrees C with 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) as a Me(.) trap gives the homolysis products Co(II)B12 and TEMPO-Me quantitatively. The 5,6-dimethylbenzimidazole axial-base-off-base-on equilibrium in ethylene glycol has an enthalpy change of -5.1 (+/-2) kcal mol(-1) and an entropy change of -10.5 (+/-4) cal mol(-1) K(-1), equilibrating between the 5,6-dimethylbenzimidazole-coordinated base-on form and the two distinct yet similar non-coordinated forms: the base-off and the so-called "tuck-in" forms. The MeB12 Co-CH3 homolysis rates indicate an activation enthalpy of 41 +/- 3 kcal mol(-1), an activation entropy of 24 +/- 6 cal mol(-1) K(-1), and an estimated methylcob(III)alamin Co-CH3 bond dissociation energy of 37 +/- 3 kcal mol(-1). This is the strongest Co-C cobamide bond measured. Comparison of the MeCbl homolysis rate constant (10(-19 +/- 4) s(-1)) extrapolated to -30 degrees C with the known reduced-methylcobamide-radical-anion values indicates rate enhancements of 10(22 +/- 4) (at -30 degrees C) following electrochemical reduction, or still over 10(15) at 25 degrees C. Such reduction provides an antibonding electron which weakens the Co-C bond from 37 kcal mol(-1) down to ca. 12 kcal mol(-1). These rate enhancements are greater than the analogous enzyme-induced Co-C cleavage rate enhancements in adenosylcobalamin (Coenzyme B12, AdoCbl)-dependent enzymes. However, electron transfer is not predicted for the mechanism of any adenosylcobalamin-dependent or methylcobalamin-dependent enzymes.