NEOPENTYLCOBALAMIN (NEOPENTYLB12) COBALT-CARBON BOND THERMOLYSIS PRODUCTS, KINETICS, ACTIVATION PARAMETERS, AND BOND-DISSOCIATION ENERGY - A CHEMICAL-MODEL EXHIBITING 10(6) OF THE 10(12) ENZYMATIC ACTIVATION OF COENZYME-B12S COBALT-CARBON BOND

A quantitative study of the thermolysis of neopentylcobalamin (NpB12) in ethylene glycol is reported, studies aimed at providing a well-defined chemical model for the 10(12) enzymic rate acceleration observed for AdoB12's (coenzyme B12's) Co-C bond homolysis. First, the mild 25-45-degrees-C thermolysis of >98% pure NpB12 in anaerobic ethylene glycol solutions containing greater-than-or-equal-to 1 equiv of the nitroxide free-radical trap TEMPO (2,2,6,6,-tetramethylpiperidinyl-1-oxy) is reported, a clean reaction (5UV-visible isosbestic points) which proceeds quantitatively to 98 +/- 2% neopentyl-TEMPO (trapped neopentyl radicals) and 99 +/- 2% Co(II)B12r. Kinetic studies establish the full rate law including an inverse, [Co(II)B12r]-1, dependence at low TEMPO concentrations, thereby unequivocally demonstrating the reversible homolysis of NpB12 to Np. and .Co(II)B12r under the conditions employed. Homolysis rate constants (k(h,obsd)), determined under excess TEMPO conditions where the homolysis step is rate-determining, yield precise activation parameters for NpB12 Co-C bond homolysis in ethylene glycol, DELTAH(double dagger)h,obsd = 28.5 +/- 0.3 kcal/mol and DELTAS(double dagger)h,obsd = 18.3 +/- 1.1 cal/mol.K. Axial-base, off-on equilibrium parameters were obtained through independent measurements, DELTAH = -4.7 +/- 0.2 kcal/mol and DELTAS = -17.8 +/- 0.9 cal/mol.K, and then used to deconvolute the NpB12 activation parameters (for the temperature-dependent shift in the base-on to base-off equilibrium); the resultant activation enthalpy and entropy for NpB12 Co-C homolysis in ethylene glycol are DELTAH(double dagger)h,on) = 32.2 +/- 0.6 kcal/mol and DELTAS(double dagger)h,on = 33 +/- 2 cal/mol.K. Key results are then discussed, specifically: the finding that NpB12 exhibits 10(6) of the 10(12) enzymic rate acceleration of coenzyme B12's Co-C bond homolysis; the proper radical-cage chemistry corrections which yield a base-on NpB12 Co-C bond dissociation energy (BDE) estimate of 28 +/- 2 kcal/mol; a comparison of the results for the three alkylcobalamins now studied by the TEMPO trapping method (adenosyl-, methyl-, and neopentylcobalamin); plus the implications of these results on current models of enzyme-accelerated Co-C bond homolysis.