The dependence of the second-order rate constants for replacement of H,O in aquahydroxocobinamide by azide at 25.0 "C, ionic strength / = 1 .O mol dm-3 (KCI) in the range pH 9-1 2 showed that dihydroxocobinamide is inert to substitution. The kinetics of substitution of bound H,O in aquahydroxocobinamide by L = cyanide, azide, pyridine, N-methylimidazole or 3-aminopropan-l -ol was investigated as a function of ligand concentration and temperature by stopped-flow spectrophotometry at pH 12.0 and a constant / of 2.0 mol dmP3 (except for 3-aminopropan-l -ol where / = 1 .O mol dmP3 because of the limited solubility of the ligand). The observed pseudo-first-order rate constants (corrected, where appropriate, for protonation of the N-donor atom of L, and the presence of inert dihydroxocobinamide) showed the onset of saturation with ligand concentration for all ligands, with the exception of 3-aminopropan-I -01. The saturation effect proves that the reaction proceeds through a dissociative activation pathway. Furthermore, the observation that the saturation rate constant, k,,, (and its activation parameters AH* and AS*), depends on the identity of L indicates that incoming L participates in the transition state. This allows the mechanism of the reaction to be identified as a dissociative interchange.The mechanism of the ligand-substitution reactions of the cobalt corrinoids continues to attract considerable attention; l-' our interest '-' has focused primarily on the mechanism of substitution of bound H,O in vitamin B,,,.$ It was demonstrated recently that at high (i.e. > 0.5 mol dm-3) concentration of L = pyridine as incoming ligand the observed rate constants saturate to a limiting value, k,,,. It was subsequently shown that for L = pyridine, 4-methylpyridine, histamine (imidazole-4-ethanamine), imidazole or methyl glycinate the values of k,,, are all different,5 and it was concluded that, contrary to the generally held view,12-17 the reactions do not proceed through a limiting dissociative (D) mechanism (for which ksat would correspond to the rate constant for the unimolecular release of water from Co"' and hence be independent of L) but through a dissociative interchange (Id) mechanism which accommodates nucleophilic participation by L in the transition state.The position along the reaction coordinate of, and hence the extent of ingression by, L into the transition state may be influenced by the nature of the trans ligand, Z. The trans effect is a well established phenomenon in the chemistry of cobalt corrinoids. For example, as the donor power of Z increases: (i) a five-co-ordinate ground state in which dmbzim is displaced from the co-ordination sphere becomes progressively more favoured; l 8 (ii) in a series of CN--Co-Z complexes, the stretching frequency of co-ordinated CN -decreases; and t Supplementary data available (No. SUP 56969, 36 pp.): primary kinetic data, see Instructions for Authors, J. Chem. Soc., Dalton Trans., 1993, Issue 1, pp. xxiii-xxviii. 1 In B, 2a (aquacobalamin) Co"' is co-ordinated in the equ...
The kinetics of substitution of bound H20 in aquacobalamin (vitamin Bla) by hydroxylamine, methyl glycinate, pyridine, 4-methylpyridine8 imidazole and histamine (imidazole-4-ethanamine) was investigated as a function of ligand concentration and temperature by stopped-flow spectrophotometry at constant ionic strength (1.0 mol dm-j) and pH. In all six cases the obsenred pseudo-first-order rate constants, corrected for protonation of the N-donor of the ligand, L, and the ionisation of bound H20 in B , , ,showed saturation at high ligand concentrations. There is a compensating change in the AH# and AS# values of the saturating rate constant, k,, but there is no general isokinetic relationship for the ligands. The dependence of the value of k,, and, in particular, the dependence of AH$ and AS$ for this rate constant on the entering ligand, L, indicate that the rate-limiting step in the reaction is not unimolecular release of H,O from Bla. The results are interpreted in terms of a dissociative interchange mechanism with nucleophilic participation of L in the transition state. The compensating effect is explained on the basis of the extent of bond formation between Co and L in the transition state. The steric bulk of L, quantified using molecular mechanics techniques in terms of the cone angle subtended by co-ordinated L at Co"', and molecular volume calculations, appears to play an important role in controlling its rate of reaction with the metal centre.The mechanism of ligand substitution reactions of cobalt corrinoids has attracted considerable not least because the cobalt(II1) ion, which is usually kinetically inert, is labilised considerably by the corrin ring (the cis labilising effect). We have been particularly interested in the mechanism of substitution of axially co-ordinated H 2 0 in aquacobalamin (vitamin B12p, here written as dmbzim-Co-H,O, where dmbzim = 5,6dimethylbenzimidazole; only the axial ligands are shown and the overall charge is neglected for convenience) by an incoming ligand, L, in aqueous solution. There has been some disagreement concerning the mechanism of these reactions. Some workers have favoured a limiting dissociative (D) mechanism in which the unimolecular dissociation of H 2 0 from the co-ordination sphere of Corn is rate limiting 3*5*8*16*17 others have favoured an interchange mechanism (Id) with participation by the incoming ligand in the transition state; 2*7 yet others 1p6*10 have simply indicated that their results may be interpreted by either mechanism.Among the evidence offered for a D mechanism is the very modest dependence of the rate constants on the identity of L.We have pointed out, however, that there are compensating changes in AH$ and A S for the reaction with a series of primary amines I9v2' and the slope of a plot of AH$ against A S happens to be such that, near room temperature, these ligands, at least, react at a similar rate. Measurements of the volumes of activation of the reactions are usually useful in settling questions such as this (and attempts have been made ...
Model structures for the pore of the potassium channels Shaker and ROMK1 are predicted. The models arise from computer simulations and suggest reasons for the striking selectivity of these channels for K+ and the blocking of ROMK1 by internal Mg2+. The modelled structure of the Shaker pore is supported by mutagenesis data. The mutagenesis experiments indicate the side chains responsible for binding to blocking agents [tetraethylammonium (TEA) and charybdotoxin (CTX)] and the model has these side chains suitably oriented for binding. An aromatic K+ binding site part way down the pore is also predicted by the Shaker pore model.
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