Solvent Cage Effects in Organocobalt Corrinoid Chemistry:  Thermal Homolysis of α- and β-(Cyanomethyl)cobinamides¹

Abstract

The equilibrium constant for the thermal isomerization of the diastereomeric alpha- and beta-(cyanomethyl)cobinamides (NCCH(2)Cbi(+)'s) has been measured over the temperature range 70-95 degrees C. Although the beta diastereomer is the thermodynamically more stable isomer, it is favored by the entropy change, but disfavored by the enthalpy change. In the presence of >/=5 x 10(-)(3) M concentration of the radical trap 4-hydroxy-2,2,6,6,-tetramethylpiperidinyloxy (4-HTEMPO), thermolysis of either isomer leads to cob(II)inamide and the trapped NCCH(2)(*) radical (NCCH(2)-4-HTEMPO) in high yield and no isomerization can be detected. The kinetics of the 4-HTEMPO-trapped thermal homolysis of alpha- and beta-NCCH(2)Cbi(+) have been studied in anaerobic glycerol/water mixtures of varying viscosity. The observed first-order rate constants for thermolysis show the expected inverse dependence on viscosity indicating that the process is at least partially diffusion controlled. From these data, the primary rate constant, k(1), for carbon-cobalt bond homolysis and the ratio of the rate constants for in-cage recombination and diffusional separation (k(c)/k(d)) can be extracted. The enthalpies of activation for Co-C bond homolysis are identical (29.0 +/- 0.3 kcal mol(-)(1)) while the entropy of activation is 2-fold higher for the alpha diastereomer. In water, the fractional cage efficiencies, F(c), are quite small (0.12 +/- 0.01, alpha; 0.049 +/- 0.008, beta) and invariant for each complex in the temperature range 75-95 degrees C. Assuming that the rate constant for diffusional separation of the caged radical pairs is the same for both isomers, the ratio of the in-cage recombination rate constants, k(c)(alpha)/k(c)(beta), can be calculated to be 2.6 +/- 0.6. This surprising kinetic preference for the alpha diastereomer results from enthalpic stabilization of the recombination transition state for the alpha diastereomer, since the beta diastereomer is entropically favored.

Diastereomeric Control in the Formation of Carbon−Cobalt Bonds in Organocobalt Corrinoids: Reactions of Cobalt(II) Corrinoids with Organic Hydroperoxides1

“…Values of the differential enthalpy and entropy of activation obtained from this plot are also given in Table along with the data previously obtained for the NCCH 2 • radical. As was previously found to be the case for NCCH 2 • , the α diastereomer is the kinetically preferred product, although for CH 3 CH 2 • it is preferred by about 7-fold at 20 °C as opposed to about 3-fold for NCCH 2 • . For both radicals, the α diastereomer is enthalpically favored but is entropically disfavored as was also the case in the ground state for the NCCH 2 Cbi + 's, but the transition state entropic preference for the β diastereomer is much smaller than the ground state preference, leading to the observed kinetic preference for the α isomer.…”

“…In contrast, thermal equilibration requires elevated temperatures (at least 70 °C) 12,13 and long incubation times. The latter is particularly problematic since strictly anaerobic conditions are required to prevent alteration of the diastereomeric ratio by oxygen-trapped thermal decomposition, the α diastereomers being considerably more thermally reactive than the β diastereomers. 8f, Thus, purging reaction samples with even the purest of inert gas streams inevitably leads to some net decomposition due to trace oxygen over the long incubation times required for thermal equilibration, and accurate diastereomeric ratios can only be obtained in sealed-tube experiments. The only significant shortcoming of the hydroperoxide method is the difficulty we have encountered in synthesizing RC(CH 3 ) 2 OOH's with electron-withdrawing R groups.…”

“…A recent study of the viscosity dependence of the kinetics of thermally-induced carbon−cobalt bond homolysis of α- and β-NCCH 2 Cbi + confirmed that such reactions are at least partly under diffusion control and proceed via the intermediacy of a solvent-caged organic radical, cob(II)inamide pair . From the viscosity dependence of these thermolysis reactions, the fractional cage efficiencies could be calculated and an estimate was obtained of the ratio of the rate constant for in-cage recombination to form the α diastereomer to that for recombination to form the β diastereomer.…”

The enzymatic activation of coenzyme B12

“…With the possible exception of the B 12 -dependent ribonucleotide reductase (vide infra) and the class I mutases, in which Co-C bond cleavage may be concerted with a subsequent hydrogen atom transfer, the enzymatic activation of AdoCbl by Co-C bond homolysis is a simple bond dissociation reaction. Although nonenzymatic, thermal homolysis of AdoCbl and other alkylcobalt corrinoids leads to a solvent caged radical pair, the diffusive separation of which is the rate determining step, 34,35,36 this cannot be the case at an enzyme active site, where there is little or no solvent, and diffusive separation of a radical pair is unlikely. Since there is no compensatory bond formation, the enzymatic activation of AdoCbl is a simple bond dissociation process, the "free energy of activation" is the bond dissociation energy (30 kcal mol −1 ), 34 and the reaction coordinate diagram is simply the portion of the Morse potential curve that raises with increasing distance (Fig.…”

Side Chain Entropy and the Activation of Organocobalamins for Carbon−Cobalt Bond Homolysis: Synthesis, Characterization, and Thermolysis of the Neopentyl Derivative of a Unique Cobalamin Analog Lacking a c Side Chain

“…Garr and Finke 52 have shown that such cage effects can be quite large indeed for alkylcobalt corrinoid homolysis in ethylene glycol. However, recent work in aqueous solution has shown quite small cage efficiencies for such species in this medium 73b…”