A computational study towards understanding the mechanism of phosphodiester cleavage by two mononuclear Zn(II) complexes.

In this study, the hydrolytic reaction mechanism of HPNP by two effective mononuclear Zn(II) catalysts was explored by using density functional calculations. With the assumption that the active catalyst is in Zn-aqua form, the water-assisted proton transfer mode was found to be energetically the most favorable one for both the catalysts among three possible reaction pathways. The rate-limiting step on this pathway is a concerted double-proton transfer, concomitant with the nucleophilic addition of the deprotonated hydroxyl group to form a five-coordinated phosphorus intermediate. A comparison of potential energy surfaces for both catalysts shows that the three amino groups in the second coordination sphere of one catalyst play an important role in stabilizing the proton transfer (or nucleophilic addition) transition state. The two coordination spheres are found to have almost the same contributions in catalyzing the phosphate ester cleavage reaction. Also, present calculations show that the water-assisted proton transfer mechanism with the catalyst L-Zn-OH(2) is more favorable in energy than the general base pathway with the active catalyst L-Zn-OH suggested previously.