The 3(rd) degree of biomimetism: associating the cavity effect, Zn(II) coordination and internal base assistance for guest binding and activation

The synthesis and characterization of a resorcinarene-based tetra(imidazole) ligand is reported. The properties of the corresponding Zn(II) complex are studied in depth, notably by NMR spectroscopy. In MeCN, acid–base titration reveals that one out of the four imidazole arms is hemi-labile and can be selectively protonated, thereby opening a coordination site in the exo position. Quite remarkably, the 4(th) imidazole arm promotes binding of an acidic molecule (a carboxylic acid, a β-diketone or acetamide), by acting as an internal base, which allows guest binding as an anion to the metal center in the endo position. Most importantly, the presence of this labile imidazole arm makes the Zn(II) complex active for the catalyzed hydration of acetonitrile. It is proposed that it acts as a general base for activating a water molecule in the vicinity of the metal center during its nucleophilic attack to the endo-bound MeCN substrate. This system presents a unique degree of biomimetism when considering zinc enzymes: a pocket for guest binding, a similar first coordination sphere, a coordination site available for water activation in the cis position relative to the substrate and finally an internal imidazole residue that plays the role of a general base.