Computational Study of the Influence of Solvent on ¹⁶O/¹⁸O Equilibrium Isotope Effects in Phosphate Deprotonation Reactions

Abstract

Results from theoretical calculations of (16)O/(18)O equilibrium isotope effects (EIEs) on deprotonation of phosphate and methyl phosphate monoanions as well as their deuterated counterparts are reported. The EIEs are calculated from the Bigeleisen equation using harmonic vibrational frequencies from several quantum mechanical methods (HF, DFT, MP2, and AM1). All methods correctly predict the qualitative trends in the EIEs related to the different isotope substitutions. However, the calculated gas-phase values are found to be systematically higher than those experimentally observed in aqueous solution. On the other hand, the addition of explicit solvent molecules (up to 24 waters) in the first solvation shells of the phosphate ion substantially improves the calculated EIE, which approaches the experimental value with increasing size of the water cluster. The large effects of surrounding water molecules on the phosphate deprotonation EIE can be explained by the strong solute-solvent interactions, which result in solvent coupled vibrational modes of the phosphate ions.

Experimental and Theoretical Multiple Kinetic Isotope Effects for an SN2 Reaction. An Attempt to Determine Transition‐State Structure and the Ability of Theoretical Methods to Predict Experimental Kinetic Isotope Effects

“…Recent work from the äquist group examined the ability of explicit solvent models to predict equilibrium oxygen isotope effects. [89] In the present study no systematic analysis of the solvation has been performed. Rather, a few readily available models were used, and the results were compared with those obtained in calculations at the same level of theory in the gas phase.…”

Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis

“…This method calculates isotope effects to high accuracy at an affordable computational cost. 20 , 21 …”

“…This method calculates isotope effects to high accuracy at an affordable computational cost. 20,21 Our computational model of the hydrolysis reaction retains all the key elements of phosphoroimidazolium hydrolysis (Scheme 1). Using the microsolvation approach, we built a series of models with up to eight explicit water molecules that occupied most hydrogen-bonding sites of the reactants.…”

“…The validity of these computational models was judged by comparing the theoretical KIEs calculated using the Bigeleisen–Mayer equation with the experimental results. Although this powerful approach has repeatedly provided critical transition-structure insights of important reactions, − its application in phosphoryl transfer reactions is limited , due to the difficulties in modeling the strong phosphate-solvent interactions . Recent advances , overcome this technical difficulty by the microsolvation approach, in which an explicit model of the solute and a few key solvent molecules is embedded in an implicit solvent model.…”

Path integral evaluation of equilibrium isotope effects

“…where superscripts r and p refer to reactant and product isotopomers, respectively. Usually, equilibrium isotope effects are computed only approximately: 1,2,3,4,5,6,7,8,9,10,11,12,13 In particular, effects due to indistinguishability of particles and rotational and vibrational contributions to the EIE are treated separately. Furthermore, the vibrational motion is approximated by a simple harmonic oscillator and the rotational motion is approximated by a rigid rotor.…”