Macrocyclic enzyme model systems. Unusual nucleophilic reactivity of un-ionized [20]paracyclophane oximes provided by hydrophobic effects

Abstract

p-Nitrophenyl decanoate and palmitate were deacylated in a neutral to acidic pH region by the nucleophilic and hydrophobic catalysis of nearly equimolar 10-hydroxyimino[20]paracyclophane (1) and 10(11)-hydroxyimino[20]paracyclophane-22-carboxylic acid (2) in aqueous dioxan or aqueous methanol. The direct nucleophilic participation of an un-ionized hydroxyimino-group was confirmed by the product analysis. The unusual nucleophilic reactivity of (1) and (2) was consistent with the following three-step mechanism: (i) pre-equilibrium complex formation between the acyl substrate and the cyclic oxime; (ii) nucleophilic attack of the neutral hydroxyimino-group of the cyclic oxime on the substrate carbonyl as effected by a proximity effect; and (iii) abstraction of the hydroxyimino-proton by the structured water molecules around the inclusion complex. The last step was rate determining on the basis of an appreciable deuterium solvent isotope effect (k_H2O/k_D2O 4.5–3.0). {10(11)-Hydroxyimino[20]paracyclophan-22-ylmethyl}trimethylammonium chloride did not show any remarkable kinetic effect in deacylation due to the structure breaking ability of the positively charged ammonium group.