The crystal structures of 10-chloroaquacobalamin perchlorate hydrate (10-Cl-H(2)OCbl.ClO(4)) (Mo Kalpha, 0.710 73 Å, monoclinic system, P2(1), a = 11.922(4) Å, b = 26.592(10) Å, c = 13.511(5) Å, beta = 93.05(3) degrees, 10 535 independent reflections, R(1) = 0.0426), 10-chlorocyanocobalamin-acetone hydrate (10-Cl-CNCbl) (Mo Kalpha, 0.710 73 Å, orthorhombic system, P2(1)2(1)2(1), a = 16.24(3) Å, b = 21.85(5) Å, c = 26.75(8) Å, 7699 independent reflections, R(1) = 0.0698), and 10-chloromethylcobalamin-acetone hydrate (10-Cl-MeCbl) (Mo Kalpha, 0.71073 Å, orthorhombic system, P2(1)2(1)2(1), a = 16.041(14) Å, b = 22.13(2) Å, c = 26.75(4) Å, 6792 independent reflections, R(1) = 0.0554), in which the C10 meso H is substituted by Cl, are reported. An unusual feature of the structures is disorder in the C ring, consistent with a two-site occupancy in which the major conformation has the C46 methyl group in the usual position, "upwardly" axial, and the C47 methyl group equatorial, while in the minor conformation both are pseudoequatorial, above and below the corrin ring. (13)C NMR chemical shifts of C46, C47, C12, and C13 suggest that the C ring disorder may persist in solution as a ring flip. Since molecular dynamics simulations fail to reveal any population of the minor conformation, the effect is likely to be electronic rather than steric. The axial bond lengths in 10-Cl-MeCbl are very similar to those in MeCbl (d(Co)(-)(C) = 1.979(7) vs 1.99(2); to 5,6-dimethylbenzimidazole, d(Co)(-)(NB3) = 2.200(7) vs 2.19(2)), but the bonds to the four equatorial N donors, d(Co)(-)(N(eq)), are on average 0.05 Å shorter. In 10-Cl-CNCbl, d(Co)(-)(C) and d(Co)(-)(NB3) are longer (by 0.10(2) and 0.03(1) Å, respectively) than the bond lengths observed in CNCbl itself, while conversely, the C-N bond length is shorter by 0.06(2) Å, but there is little difference in d(Co)(-)(N(eq)). The Co-O bond length to coordinated water in 10-Cl-H(2)OCbl(+) is very similar to that found in H(2)OCbl(+) itself, but the d(Co)(-)(NB3) bond is longer (1.967 vs1.925(2) Å), while the average d(Co)(-)(N(eq)) is very similar. The coordinated water molecule in 10-Cl-H(2)OCbl(+) is hydrogen bonded to the c side chain carbonyl oxygen, as in H(2)OCbl(+). NMR observations indicate that the H bond between coordinated H(2)O and the c side chain amide persists in solution. The equilibrium constant, K(Co), for coordination of bzm to Co(III) is smaller in 10-Cl-MeCbl and 10-Cl-CNCbl than in their C10-unsubstituted analogs (181 vs 452; 4.57 x 10(3) vs 3.35 x 10(5)), but could not be determined for 10-Cl-H(2)OCbl because hydrolysis of the phosphodiester is competitive with the establishment of the base-off equilibrium. Substitution of H by Cl at C10 causes the bands in the electronic spectrum of 10-Cl-XCbl complexes to move to lower energy, which is consistent with an increase in electron density in the corrin pi-conjugated system. This increased electron density is not due to greater electron donation from the axial ligand as bonds between these and the metal are either lon...

To probe the cis effect of the corrin macrocycle in vitamin B12 derivatives, equilibrium constants for the substitution of coordinated H2O in aquacobalamin (vitamin B12a, H2OCbl+) and in aqua-10-chlorocobalamin, H2O-10-ClCbl+, (in which Cl has replaced the C10 H) by an exogenous ligand, L (L = an anion, NO2-, SCN-, N3-, OCN-, S2O3(2-), NCSe- or a neutral N-donor, CH3NH2, pyridine, imidazole) have been determined. The cis influence reported in the electronic spectra of the cobalamins is observed in the spectra of L-10-ClCbls as well. Anionic ligands bind more strongly to H2O-10-ClCbl+ than to H2OCbl+ with log K values between 0.10 and 0.63 (average 0.26) larger; the converse is true for the neutral N-donor ligands, where log K is between 0.17 and 0.3 (average 0.25) smaller. Semi-empirical molecular orbital (SEMO) calculations using the ZINDO/1 model on the hydroxo complexes show that charge density is delocalised from the axial donor atom to the metal and Cl. This explains why coordinated OH- is a poorer base in HO-10-ClCbl than in HOCbl and the pK(a) of H2O-10-ClCbl+ is lower than that of H2OCbl+. It further explains why, because of the ability of the metal in concert with the C10 Cl to accept charge density from the ligand, an anionic ligand will bind more strongly to Co(III) in H2O-10-ClCbl+ than in H2OCbl+. The kinetics of the replacement of coordinated H2O by two probe ligand, pyridine and azide, were determined. The rate constants for substitution of H2O in H2O-10-ClCbl+ by pyridine show saturation, whilst those for substitution by N3- do not; this is inconsistent with a purely dissociative mechanism and the reactions proceed through an interchange mechanism. The values of the activation parameters are more positive for the reaction between these ligands and H2OCbl+, than for their reaction with H2O-10-ClCbl+. This is interpreted to mean that the transition state in the reaction of H2O-10-ClCbl+ occurs earlier along the reaction coordinate. In the temperature range studied, H2O-10-ClCbl+ reacts more slowly with py and N3- than does H2OCbl+. SEMO calculations indicate that as the Co-O bond to the departing H(2)O molecule is stretched, the charge density on Co in H2OCbl+ is always lower than on Co in H2O-10-ClCbl+. This suggests that the former is a better electrophile towards the incoming ligand, and offers an explanation for the kinetics observations.