Macrocyclic enzyme model systems. Concurrent nucleophilic–electrostatic bifunctional catalysis by [20]paracyclophanes in deacylation of p-nitrophenyl carboxylates

Abstract

Deacylation of p-nitrophenyl laurate (PNPL) and palmitate (PNPP) was accelerated in alkaline solution by the presence of a 10-hydroxyimino[20]paracyclophane derivative. A [20]paracyclophane which bears a quaternary ammonium group on the benzene ring and a nucleophilic hydroxyimino-group on the polymethylene bridge (2a) greatly enhanced the reaction rate due to an electrostatic effect provided by the positively charged substituent, whereas a 10-hydroxyimino[20]paracyclophane derivative bearing a carboxylate group on the benzene group (2c) enhanced the rate only slightly and the parent oxime (2b) showed the intermediate catalytic activity. The kinetics of deacylation are consistent with a reaction mechanism which involves pre-equilibrium complex formation between an ester substrate and a paracyclophane oxime, followed by pseudo-intramolecular acyl transfer from the incorporated substrate to the deprotonated hydroxyimino-group of a paracyclophane macrocycle. The paracyclophane oximes exhibited comparatively large binding constants (10³–10⁵ l mol^–1) in the decreasing sequence (2b) > (2c) > (2a). The reactivity of the subsequent intracomplex acyl transfer was characterized by the nature of an electric charge on the benzene group and decreases in the sequence (2a)(2b) > (2c). The apparent second-order rate constant for acylation of (2a) with PNPL exceeds that for the reaction of chymotrypsin with p-nitrophenyl acetate. The ammonium salt (2a) is thus claimed as a novel enzyme model which exhibits both favourable hydrophobic binding ability towards an appropriate ester substrate and nucleophilic–electrostatic bifunctional catalysis giving rise to significant rate acceleration in its decomposition.