Synthesis and reactivity of a C₃-symmetric trinuclear zinc(II) hydroxide catalyst efficient at phosphate diester transesterification

Inspired by trinuclear Zn(II) sites in enzymatic systems, a ligand system containing three preorganized (2-pyridyl)methyl piperazine moieties anchored onto a rigid C₃-symmetric triphenoxymethane platform has been developed for preorganizing three zinc ions into an environment conducive to intramolecular interaction. Zinc(II) binding by this ligand has been analyzed by means of potentiometric measurements in 50% (v/v) CH₃CN–H₂O solutions. Subsequently a C₃-symmetric trinuclear Zn(II) hydroxide complex of the C₃-symmetric ligand was synthesized and fully characterized using NMR spectroscopy and X-ray crystallography. This complex induces a 16900-fold rate enhancement in the catalytic cyclization of the RNA model substrate, 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP, pH 6.7, 25 °C) over the uncatalyzed reaction with multiple catalyst turnovers. The observed differences in the pH-rate profile can be attributed to the varying concentration of various trinuclear zinc species. The trinuclear Zn(II) catalyst exhibits a higher hydrolytic activity compared to its mononuclear analogue. The reactivity and structural features of this trinuclear Zn(II) complex will be discussed.