Dinuclear Zn^II and mixed Cu^II–Zn^II complexes of artificial patellamides as phosphatase models

Abstract

The patellamides (cyclic pseudo-octapeptides) are produced by Prochloron, a symbiont of the ascidians, marine invertebrate filter feeders. These pseudo-octapeptides are present in the cytoplasm and a possible natural function of putative metal complexes of these compounds is hydrolase activity, however the true biological role is still unknown. The dinuclear Cu^II complexes of synthetic patellamide derivatives have been shown in in vitro experiments to be efficient hydrolase model catalysts. Many hydrolase enzymes, specifically phosphatases and carboanhydrases, are Zn^II-based enzymes and therefore, we have studied the Zn^II and mixed Zn^II/Cu^II solution chemistry of a series of synthetic patellamide derivatives, including solution structural and computational work, with the special focus on model phosphatase chemistry with bis-(2,4-dinitrophenyl)phosphate (BDNPP) as the substrate. The Zn^II complexes of a series of ligands are shown to form complexes of similar structure and stability compared to the well-studied Cu^II analogues and the phosphatase reactivities are also similar. Since the complex stabilities and phosphatase activities are generally a little lower compared to those of Cu^II and since the concentration of Zn^II in Prochloron cells is slightly smaller, we conclude that the Cu^II complexes of the patellamides are more likely to be of biological importance.