An experimental and theoretical study of the mechanism of cleavage of an RNA-model phosphate diester by mononuclear Zn(II) complexes

Kinetic investigations and density functional theory calculations were used to explore the mechanism of the cleavage of the RNA analogue 2-hydroxypropyl-p-nitrophenyl phosphate promoted by mononuclear Zn(II) complexes of polyamine ligands, focusing the attention on the attack of the 2-hydroxyl to the phosphorous atom. The results obtained indicate that mononuclear complexes of tridentate polyamine ligands are more reactive than the tetradentate ones notwithstanding similar Lewis acidity. Three reaction pathways were found corresponding to the three reaction mechanisms so far proposed: general base catalysis by a metal coordinated species, specific base catalysis and specific base catalysis involving coordination of the 2-hydroxyl to the metal ion. The three mechanisms have similar reaction barriers with a slightly lower one for the general base catalysis one. Among the two specific base catalysis mechanisms, which are in agreement with previous experimental observation of low isotopic solvent kinetic effects for the reaction, the one involving metal coordination of the substrate alcoholic group appears the more likely and is also capable to explain the higher activity of mononuclear complexes of triamine ligands compared with tetramine ones.