Acta Phys. -Chim. Sin. ›› 2010, Vol. 26 ›› Issue (04): 1034-1042.doi: 10.3866/PKU.WHXB20100447


Coorperativity between Metals, Ligands and Solvent: a DFT Study on the Mechanism of a Dizinc Complex-Mediated Phosphodiester Cleavage

FAN Yu-Bo, GAO Yi-Qin   

  1. Department of Chemistry, Texas A&MUniversity, College Station, TX 77843-3255, USA; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
  • Received:2010-01-14 Revised:2010-03-05 Published:2010-04-02
  • Contact: GAO Yi-Qin


Density functional theory (DFT)-Tao-Perdew-Staroverov-Scuseria (TPSS) functional calculations on dizinc complex-mediated phosphodiester cleavage indicate a general base catalytic mechanism. 2-hydroxylpropyl-4-nitrophenyl phosphate (HPNP) favors the bridging of two Zn ions by the formation of two coordination bonds between terminal phosphate oxygens and Zn ions. The Zn-bound hydroxide deprotonates the hydroxyl on the side chain of HPNP and consequently the alkoxide is stabilized by coordination to a Zn ion and a hydrogen-bond to Zn-bound water. A water molecule is tightly bound to two amino protons in the bis(1,4,7-triazacyclononane) ligand and this determines the orientation of HPNP during a nucleophilic attack to form a trigonal bipyramidal PO5 intermediate and it also weakens the bond between phosphorus and the phenolate, which makes the leaving of the latter easier. The phenolate formed after the collapse of the five-coordinated phosphorus intermediate easily coordinates to a Zn ion. Surprisingly, the stabilizing solvent effect for the transition state after the formation of the PO5 intermediate is much stronger (at least 42 kJ·mol-1) than that of all other species as they have solvation energies that fluctuate around 12.6 kJ·mol-1. Thus, the overall free energy barrier for this reaction after reactant-binding and before product release is about 17.0 kJ·mol -1, which is too low to be rate-determining. The rate-determining step is very likely part of the release process of the products. Based on various calculations, we discuss possible reasons for the different catalytic efficiencies of the dizinc complex and the enzymes.

Key words: Zinc, Phosphodiester cleavage, Density functional theory, TPSS, Mechanism