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Article

Thermodynamic Origin of the Increased Rate of Hydrolysis of Phosphate and Phosphorothioate Esters in DMSO/Water Mixtures

Supporting Info

Kerensa Sorensen-Stowell and Alvan C. Hengge*

Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322-0300

J. Org. Chem., 2006, 71 (19), pp 7180–7184

DOI: 10.1021/jo060896b

Publication Date (Web): August 23, 2006

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, hengge@cc.usu.edu

Abstract

The hydrolysis rates of the dianions of phosphate and phosphorothioate esters are substantially accelerated by the addition of polar aprotic solvents such as DMSO and acetonitrile. The activation barrier ΔG is smaller due to a lower enthalpy of activation. The enthalpy of transfer of p-nitrophenyl phosphate (pNPP) and p-nitrophenyl phosphorothioate (pNPPT), from water to 0.6 (mol) aq DMSO (60 mol % water in DMSO) were measured calorimetrically. The enthalpies of activation for the hydrolysis reactions in the two solvents permitted the calculation of the enthalpy of transfer of the transition states. This transfer is thermodynamically favorable for both the reactants and the transition states but is more favorable for the transition states. In the case of pNPP, the enthalpy of transfer of the reactant is −23.9 kcal/mol, compared to −28.3 for the transition state. The difference is greater for pNPPT, where the enthalpy of transfer of the reactant is −23.2 kcal/mol and that for the transition state is −35.3. The results show that the reduced enthalpies of activation in both hydrolysis reactions arise not from a destabilization of the reactants in the mixed solvent, but from the fact that the enthalpy of transfer of the transition states to the mixed solvent is significantly more negative than the enthalpy of transfer of the reactants.