Facilitated tetrahedral intermediate formation

It is apparent that steric bulk and stereochemical control of mechanism operates in the alkaline hydrolysis of methyl 8-acyl-1-naphthoates. The proximity and favourable orientation of the carbonyl group at the 8-position facilitates intramolecular catalysis from this group. However, the formation of the tetrahedral intermediate at the 8-acyl carbonyl group has distinct... 

Evidence for the tetrahedral intermediate includes a Hammett p constant of+2.1 for the deacylation reaction of substituted benzoyl-chymotrypsins and the formation of tetrahedral complexes with many inhibitors, such as boronates, sulfonyl fluorides, peptide aldehydes, and peptidyl trifluoromethyl ketones. In these last the chemical shift of the imidazole proton is 18.9 ppm, indicating a good low-barrier H-bond, and the pJQ of the imidazolium is 12.1, indicating that it is stabilized by 7.3 kcal mol 1 compared to substrate-free chymotrypsin. The imidazole in effect is a much stronger base, facilitating proton removal from the serine. 

A direct substitution mechanism was indicated for the 2-pyridone catalysis of aminolysis of methyl acetate by methylamine." This mechanism is represented in Figure 7.9. It avoids a tetrahedral intermediate and describes a concerted displacement process that is facilitated by proton transfer involving 2-pyridone. Two very closely related TSs involving either the 2-hydroxypyridine or 2-pyridone tautomers were found. These TSs show extensive cleavage of the C-0 bond (2.0-2.2 A) and formation... 

Tabushi, K Kimura, Y., Yamamura, K. Facilitated formation of tetrahedral intermediate in esterase action by a water soluble heterocyclophane in Chemical Approaches to Understanding Enzyme Catalysis, (ed. Green B. S., Ashani, Y., Chipman, D.) p. 328, Elsevier, Amsterdam 1982... 

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