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.
Hydrodeamination of the c-amino derivative, 5, of cyanocobalamin (CNCbl) with hydroxylamine-O-sulfonic acid in aqueous base leads to an extensively rearranged product instead of the c side chain truncated derivative, 1, expected from simple deamination. The rearranged product (CNCbl-8-butanamide) crystallizes in the orthorhombic system, space group P2(1)2(1)2(1) with unit cell dimensions a = 16.041(11), b = 21.94(2), and c = 25.43(2) Å. It is devoid of substituents at corrin ring C(7) but quarternized at C(8) with an "upwardly" pseudoaxial methyl group and a d side chain expanded by one methylene group to a butanamide. The corrin ring of this rearranged derivative is significantly flatter (corrin ring fold angle 9.9 degrees ) than CNCbl itself (fold angle 18.0 degrees ). Conversion of CNCbl-8-butanamide to its neopentyl derivative (NpCbl-8-butanamide), a NpCbl analog which lacks a c acetamide side chain, permits a quantitative assessment of the influence of thermal motions of the c side chain on the entropy of activation for carbon-cobalt bond thermal homolysis in NpCbl. NpCbl-8-butanamide is shown to thermolyze homolytically to give products derived from the Np(*) radical quantitatively. The kinetics of the thermolysis of NpCbl-8-butanamide were studied in aerobic aqueous solution at temperatures between 15 and 45 degrees C. After correction of the observed first-order rate constants for the presence of the essentially unreactive base-off species using an established NMR method, an Eyring plot yields the activation parameters DeltaH()(on) = 26.7 +/- 0.1 kcal mol(-)(1) and DeltaS()(on) = 13.2 +/- 0.2 cal mol(-)(1) K(-)(1). While the enthalpy of activation is slightly reduced (6%) from that of NpCbl, the entropy of activation is reduced by 6.1 +/- 0.6 cal mol(-)(1) K(-)(1), or 32 +/- 3%. The c side chain thus contributes about one-third of the total entropic activation of NpCbl for carbon-cobalt bond homolysis, and the entropy of activation for this reaction is probably dominated by changes in the thermal motions of the "upwardly" pseudoaxial a and c acetamide side chains as the reaction progresses.
Brown
Kenneth L.
KL
Departments of Chemistry, Ohio University, Athens, Ohio 45701, Jackson State University, Jackson, Mississippi 39217, and Mississippi College, Clinton, Mississippi 39085.
Cheng
Shifa
S
Zubkowski
Jeffrey D.
JD
Valente
Edward J.
EJ