A catalyst for ester hydrolysis showing electrostatic and hydrophobic binding properties

Abstract

. Can. J. Chem. 54, 2745Chem. 54, (1976. The steroid 17p-(4-imidazoly1)-5~~-androstane-3p,l lp-diamine, l a , R = H , acts as a catalyst for the hydrolysis of aryl esters. For a series of aryl acetates, 2a-/I, at 1 M ionic strength, log kz for l a catalyzed hydrolysis is linearly related to log kz for imidazole catalyzed hydrolysis, with only 2d, 4-acetoxy-3-nitrobenzoate, deviating: at zero ionic strength, all anionic substrates show positive deviations, and a cationic substrate shows a negative deviation. This is interpreted in terms of a stringent geometrical requirement for strong electrostatic catalysis. With favorable geometry, a 1 :1 electrostatic attraction can lead to a 15 fold rate enhancement ( r = 0). For a series of arylpropionate esters 3a-c, rate constants for l a catalyzed hydrolysis show a small but progressive increase with increasing size of the aryl group: after correcting for substrate reactivity and electrostatic interactions, this hydrophobic effect is independent of the leaving group. l b (R = isopropyl) was prepared to determine the rate of reaction at N-3 of the steroidal imidazole ring: this is the more hindered nitrogen but also the more suitable for hydrophobic binding. l b was markedly less reactive than l a , but showed larger hydrophobic effects. Detailed analysis suggests that the potential hydrophobic rate enhancement for the interaction of a phenanthryl group with the lower surface of a steroid is about 160-fold. This study provides guidelines for the design of enzyme models of greater catalytic efficiency.

A water soluble dimeric steroid with catalytic properties. Rate enhancements from hydrophobic binding

“…We were surprised to find that the rate constants for the reaction of the ester of 3-(3-phenanthry1)propionic acid with a cationic phenol were faster than for the corresponding ester of an anionic phenol. This contradicts our previous findings concerning the electrostatic effects on catalysis by 8 (4). However, the rate effect shows up consistently for all three cationic esters of arylpropionic acids.…”

“…For the phenanthryl substrate this rate enhancement amounts to a factor of 1.1 x 10'-fold, or 6.9 kcal/mol in stabilization. As we have observed before (4,5) this is attributed to the crowding and torsional strain involved in achieving a transition state where the imidazole has attacked the ester carbonyl and simultaneously the aryl substituent is arranged parallel to the hydrophobic face of the steroid bearing the imidazole. Despite this unfavorable interaction we have now achieved an observable effect of 550-fold in rate.…”

“…from an 1 1-P-amide, but could be hydrolyzed in acid (4). we initially tried this blocking group, as outlined in Scheme 2.…”

“…We have reported studies of various catalytic molecules based on a steroid skeleton, which provided a hydrophobic binding surface (1)(2)(3)(4). By linking two steroid moieties in a dimeric catalyst we were able to achieve larger rate enhancements (3, but encountered severe experi~rlental difficulties as a result of the very low solubility of this catalyst.…”

Aromatic sulphonates and the hydrolysis of 2-(p-nitrophenoxy)tetrahydropyran

“…This is twice the value expected from the Bronsted plot for a simple carboxylic acid of pK, 3.1. The enhancement is probably small enough to be attributable to experimental error but is also consistent with the sort of enhancement which might be expected for hydrophobic binding involving only one phenyl group (16).…”