B-12 MODELS WITH HIGHLY DISTORTED N-4 EQUATORIAL LIGATION AND A CO-C-N RING - STRUCTURAL ASSESSMENT OF THE STERIC INFLUENCE OF BENZIMIDAZOLE AND IMIDAZOLE AXIAL LIGANDS

In human B-12 enzymes, a histidyl imidazole is the lower axial ligand instead of the benzimidazole of the coenzymes, We have: explored the d ifferences in the binding interactions of these ligands using a novel class or organocobalt models, [LCo(N-CH2-CHEL)]X, with an unusually sp acious lower coordination site created by a rare Cu-C-N ring. We now c ompare two new analogs, 1 (L = 1,5,6-trimethylbenzimidazole = Me(3)Bzm ) and 2 (L = N-methylimidazole N-MeImd), with the first analog, 3 (L = pyridine = py). The three structures (X - PF6 for 1 and 2; X = CIO4 f or 3) have similar geometrical parameters for the ring atoms (N(2), Co , C(12)). A pocket under the Co-C-N group is created by the raised pos ition of N(2) above the plane of the other three equatorial N donors, the cis oxime N, N(1), the trans oxime N, N(4), and the cis imine N, N (3). A net upward bending is clearly shown by the sum of the four cis N-Co-N bond angles involving the L ligating atom, N(5). The sum is sim ilar to 23 degrees more in the new models than in related imine/oxime- type (I/O) models. The distortions around N(5) differ significantly fo r the three structures, The Co-N(5) bond of Me(3)Bzm complex 1 is tilt ed furthest away from the Co-C-N pocket, and the N(5)-Co-N(2) angle is 111 degrees. The value of the N(5)-Co-N(4) angle (96 degrees) is clos e to that of the related angle (95 degrees) in the I/O model, [Me(3)Bz mCo((DO)(DOH)pn)CH3]PF6. In contrast, the N(5)-Co-N(4) angle of the N- MeImd and the py complexes, 2 and 3, is larger than that in I/O comple xes, suggesting that these L. ligands are small enough to move toward the packet. These and other structural parameters suggest clear differ ences between the steric interactions of the equatorial ligand with th e imidazole and with the benzimidazole ligands. These complexes have u nusual H-1 NMR properties, e.g. a large remote isotope effect on some CK signals after exchange of the oxime OH to OD. At pH 13, the N4C che late of [H2OCo(N-CH2-CHEL)](+) reverts, in part, to the classical I/O N-4 chelate, suggesting a stepwise mechanism involving C-N bond cleava ge to form a Co-CH2OH intermediate, which then undergoes base-catalyze d CD-C bond cleavage.