Macrocyclic enzyme models. A metallo[10.10]paracyclophane bearing two imidazolyl groups as an efficient, bifunctional catalyst for ester hydrolysis
Abstract
The CuII complex of [10.10]paracyclophane with one imidazolyl group on each benzene ring (Im2[10.10]PCPCuII) effectively catalyses the hydrolysis of p-nitrophenyl esters with a long alkyl chain by a mechanism involving acylation–deacylation cycles. Facile, CuII-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]PCPCuII→(Im)(ImCOR)[10.10]PCPCuII) is followed by deacylation of the resulting monoacylcyclophane intermediate, which is facilitated by the imidazole-bound CuII 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 CuII 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 CuII ion (rate constant < 10–5 s–1) under the experimental conditions. The co-ordination of Im2[10.10]PCPCuII and the role of cyclophane-bound copper in the acylation and deacylation steps are discussed.