BINDING OF THE LOPSIDED 1,5,6-TRIMETHYLBENZIMIDAZOLE LIGAND TO INORGANIC AND ORGANOMETALLIC COBALOXIME B-12 MODELS

The interaction of the lopsided dimethylbenzimidazole ligand with the corrin ligand in cobalamins (Cbls) may be one of the structural features involved in Co-C bond cleavage during B-12-dependent enzymic processes. Models of B-12 compounds usually contain alkyl ligands to mimic the coenzymes. However, the inductive effect of the Co on the benzimidazole ligand should be most pronounced when the trans influence of the other axial ligand is weak, e.g. Cl. In this report we describe the synthesis and three-dimensional structures of Me3BzmnCo(DH)2Cl (I) and several alkylcobaloximes, Me3BzmCo(DH)2R(where Me3Bzm = 1,5,6-trimethylbenzimidazole,DH = the monoanion of dimethylglyoxime, and R = CH2NO2 (II), R = CH3 (III), and CH(CH3)2 (IV)). The X-ray results suggest that this benzimidazole ligand does not have unusual bulk and closely resembles pyridine in steric effect. The geometry at the Co-coordinated N of Me3Bzm is characterized by large angular distortions. However, the distortions were not very dependent on the trans ligand. A two-term expression has been reported previously to explain the dependence of the C-13 NMR chemical shifts for the alpha-ribazole (dimethylbenzimidazole-containing) moiety in Cbls on changes in the trans axial ligand. The first (through-bond) inductive term relates the inductive effect of the cobalt center to that of the proton. The second (through-space) anisotropic term relates the effects of changes in structure and cobalt anisotropy on chemical shift. We attempted to use an analogous expression to fit our structural and NMR data on Me3Bzm cobaloximes with trans ligands of greatly different trans influence. The proton inductive effects were not useful for explaining the cobalt inductive effects, since the C-13 NMR signal for B2 (the C between the two benzimidazole N's) moved down field on coordination in our models but upfield on coordination in Cbls. Protonation causes the B2 signal to move upfield. Therefore, with our extensive data, we developed a new empirical inductive term which gave excellent fits of our data, expressed as coordination shifts. Coordination shifts are the differences in shift of the free and coordinated ligand. The possible significance of this new term is discussed in the tight of the finding that it gave values consistent with the effects of other metal ions on the B2 coordination shifts and with other measures of the influence of axial ligands on the properties of the cobalt center. Furthermore, the upfield coordination shift of B2 in Cbls can now be confidently attributed to corrin ring anisotropy; the shift is only slightly modulated by cobalt inductive and anisotropic effects. Moreover, the small dependence of the B2 shift on the trans influence of the other axial ligand (the ligand-responsive shift) cannot be rationalized with the published two-term proton-based expression. With our new interpretation, a consistent description of ligand-responsive shifts emerges for both Cbls and B-12 models. Finally, our reinterpretation of factors influencing C-13 NMR shifts also accounts for some significant features of the IH NMR spectra of Cbls.