W0231

Coenzyme B₁₂: Finding the Smoking Gun. Anne E. Fischer and Virginia B. Pett, The College of Wooster, Wooster, OH 44691.

Much research has been done on coenzyme B₁₂, and B₁₂ model compounds. Nevertheless, the complete mechanism for biological activity—the smoking gun, of B₁₂ coenzyme—is not well understood. Comparison of crystallographic and theoretical data of Wooster, Costa, and cobaloxime B₁₂ analogues in this study gives evidence that both steric and electronic influences affect structure. The structure of Wooster model compound [αCo{(DO)(DOH)bn} β] where α is imidazole and β is propyl, was solved via crystallographic methods. The four-carbon bridge of the equatorial (DO)(DOH)bn ligand was bent towards the imidazole on the α face of the molecule. The equatorial nitrogen plane was bent towards the β alkyl ligand (α = 9.96°) and the cobalt atom was below this plane (d = 0.046 Å). The Co–α distance was 2.071(5) Å while the Co–β distance was 2.020(7) Å.

Theoretical B₁₂ model compounds (semi-empirical calculations) provided adequate data for comparison with crystallographic structures. Co–α and Co–β bond lengths of the theoretical molecules were comparable to those in crystallographic structures; substantial structural characteristics, such as equatorial ring fluction, were generally similar between theoretical and crystallographic data.

Comparison of Co–β bond length in Wooster, Costa, and cobaloxime models with distance constraints on the Co–α imidazole ligand showed evidence for the classical trans effect: as the Co-α bond was manually lengthened, the Co–β bond shortened. However, steric interactions of the α and β ligands with the equatorial macrocycle are also important. As the Co–α distance lengthened, the equatorial ligand bent more towards the α face, reducing steric interactions between the β ligand and the equatorial macrocycle. The extent to which electronic or steric effects influence molecular structure in these compounds is unclear.

Theoretical B₁₂ Wooster model complexes with β as ethyl, and α varied along the trans-directing series, showed no clear relationship between the Co–β bond length and the σ-electron donating power or the π-electron acceptance capacity of the α axial ligand. Among a series of cobaloxime analogues with β as P(OCH₃)₃ and α varied along a series of ligands with increasing rate of reactivity, the Co–β bond length was found to be independent of rate constant. This research suggests that studies focusing on the length of the Co–β bond as an indication of reactivity may not provide a full explanation of mechanistic influences.