Macrocyclic enzyme models. A metallo[10.10]paracyclophane bearing two imidazolyl groups as an efficient, bifunctional catalyst for ester hydrolysis

Abstract

The Cu^II complex of [10.10]paracyclophane with one imidazolyl group on each benzene ring (Im₂[10.10]PCPCu^II) effectively catalyses the hydrolysis of p-nitrophenyl esters with a long alkyl chain by a mechanism involving acylation–deacylation cycles. Facile, Cu^II-assisted acyl transfer from the bound substrate to one of the imidazolyl groups with an apparent second-order rate constant of 1.3 × 10³ l mol^–1 s^–1 in ethanol–dioxan–water (20.5 : 1 : 78.5 v/v) at 40.0 ± 0.1 °C, pH 8.12, and µ 0.10 (KCl)(Im₂[10.10]PCPCu^II→(Im)(ImCOR)[10.10]PCPCu^II) is followed by deacylation of the resulting monoacylcyclophane intermediate, which is facilitated by the imidazole-bound Cu^II ion, with a first-order rate constant of ≳ 10^–3 s^–1. The occurrence of catalysis was confirmed from observations for the monoimidazole analogue of [20]paracyclophane, Im[20]PCP : (a) the nucleophilic reactivity of an imidazolyl moiety in Im[20]PCP is masked upon co-ordination with Cu^II although the resulting complex still catalyses hydrolysis by a different mechanism, and (b) the acylated intermediate, (ImCOR)[20]PCP, does not undergo deacylation in the presence and absence of Cu^II ion (rate constant < 10^–5 s^–1) under the experimental conditions. The co-ordination of Im₂[10.10]PCPCu^II and the role of cyclophane-bound copper in the acylation and deacylation steps are discussed.