Electrostatic catalysis stabilisation

That the rate acceleration due to the carboxyhc acid was intramolecular general acid catalysis, and was not the kinetically equivalent A, reaction of the anion, in which the transition state was stabilised by electrostatic catalysis (or syn nucleophilic attack) was established by the following pieces of evidence. 

The elucidation of the X-ray structure of lysozyme provided the first direct information about the structure of an enzyme-substrate complex (Blake et al., 1967). This and other biochemical studies led to the proposal of three major catalytic factors general acid catalysis, steric strain and electrostatic stabilisation. It was found that the effect of steric strain is unlikely to be important because it can be relaxed by small shifts in the substrate and enzyme geometries (Warshel and Levitt, 1976 Pincus et al., 1977). This point was further established by quantitative FEP calculations (Warshel, 1991). On the other hand, it was found that electrostatic interactions play a very important role in the enzymatic reaction. The total electrostatic stabilisation of the carbonium transition state, relative to the corresponding stabilisation in solution, was found to be 29 kJ/mol (cf. Figure 12., Warshel, 1978). This value appears to account... 

Careful analysis of the energetics of enzyme catalysis leads one to conclude that it must involve electrostatic stabilisation of transition states. It is also becoming clear that this is done by active sites with preoriented polar environment that can be viewed as a "supersolvent" for the transition state (Warshel, 1981). 

Catalysis by micelles of the hydroxide-ion catalysed hydrolysis of substrates appears to be qualitatively understood on the basis of a concentration effect of reactant on, or around, the micelle surface and need not necessarily involve a dilference in the free energies of activation in the micelle and bulk phase. That is not to say that the cationic micelles could not and do not cause electrostatic stabilisation of the transition state. The cationic micelle surface can act as an electrostatic sink for the anionic intermediate leading to its stabilisation, but a rate enhancement requires preferential stabilisation of this intermediate compared with the reactant. The small rate enhancement of the micelle catalysed reaction, about 50-fold, is equally well explained by considering that the increased concentration of reactants at the micelle surface leads to a higher observed rate. Incorporation of the reactants into a limited volume decreases the entropy loss that is associated with bringing reactants together in the transition state and this leads to an increase in the pseudo first-order rate constants in the presence of surfactant micelles. Cationic micelles of CTAB have also been shown to facilitate the alkaline hydrolysis of the cephalosporin, cephalexin (Yatsuhara el al., 1977). 

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