Dinuclear metallo-phosphodiesterase models: application of calix[4]arenes as molecular scaffolds

Abstract

An important goal in supramolecular chemistry is the synthesis of molecules that exhibit catalytic activity analogous to the activity of enzymes. In this respect, studies toward the biomimetic catalysis of phosphate diester cleavage have received particular attention. In nature this process is catalyzed by enzymes that possess often two or three divalent metal ions in their active sites. In order to mimic the active sites of these metallo-phosphodiesterases chemists generally attempt to connect ligated metal ions by a molecular spacer in such a way that the metal–metal distance matches with the anionic pentacoordinate phosphorus transition state. However, in contrast to enzymes, which bind the transition state by multiple contacts via an induced fit mechanism, many of the low molecular weight model systems exhibit only minor catalytic activity due to lack of catalytic groups and too much rigidity or flexibility. Our approach is to use calix[4]arenes as a molecular scaffold for the dynamic preorganization of multiple catalytic groups. In this review models for dinuclear metallo-phosphodiesterases and the use of calix[4]arenes in such models are described.