Alexander A. Rashin

Incorporation of reaction field effects into density functional calculations for molecules of arbitrary shape in solution

Abstract An attempt is made to combine continuum reaction field approaches with DFT ab initio calculations for quantitative evaluation of salvation effects in chemical processes. The formalism of the combined method is delineated along with its possibilities and limitations, and applied to several small model systems. It is found that DFT can provide dipole moments in vacuum and in solution (e.g., for water) with accuracies (0.1 D) that have not been reported with other methods. The results obtained suggest that agreement within

Quantitative evaluation of hydration thermodynamics with a continuum model

˜1 kcal/mole can be expected between calculated and experimental hydration enthalpies of polar unchanged solutes. The results for ions are not as consistent as for dipolar molecules, suggesting that accurate multipole representations of the electron density of solutes may be required especially for ionic solutes.

A view of thermodynamics of hydration emerging from continuum studies.

We attempt to analyze whether experimental entropies, enthalpies and free energies of hydration of small uncharged molecules can be quantitatively rationalized with a continuum model including a classical reaction field formalism. We find that a simple proportionality to accessible surface with five different atom types allows satisfactory (within 1-1.5 kcal/mol) reproduction of hydration entropies (T delta S) of over 40 solutes. The agreement with experiment can possibly be improved if proximity effects and configurational contributions to transfer entropies are taken into account. In calculations of hydration enthalpies a reasonable agreement with experimental data can be obtained only when solute polarizability is taken into account. Electrostatic contributions to calculated hydration enthalpies exhibit strong dependencies on both the magnitude and the direction of molecular dipole moments. We demonstrate that for 20 molecules with experimentally measured vacuum dipole moments density functional calculations with DZVPD basis set including diffuse functions on d-orbitals allows prediction of experimental dipole moments within 0.1 D. At a fixed direction of the molecular dipole moment, mu, the electrostatic component of hydration enthalpy varies as mu 2. Thus an uncertainty of 0.1 D corresponds to uncertainties of 0.5-0.7 kcal/mol in hydration enthalpies of most small dipolar solutes. A 30 degree change in the direction of the molecular dipole together with the corresponding change in the quadrupole moment can result in a change of hydration enthalpy of 3 kcal/mol. Changes in the quadrupole moment alone can result in hydration enthalpy changes of over 1 kcal/mol. Representations of multipole expansions by point charges on nuclei fitted to molecular electrostatic potentials cannot accurately reproduce all these factors. Use of such point charges in calculations of hydration enthalpies predictably leads to discrepancies with experiment of approximately 3 kcal/mol for some solutes. However, errors in hydration enthalpies and hydration entropies are usually compensating leading in most cases to agreement between calculated and experimental free energies of hydration within 1.5 kcal/mol.

Reevaluation of the Born model of ion hydration

Main physical-chemical features of hydration found in continuum studies and possible limitations of the method are analyzed. Particular attention is given to: the choice of thermodynamic observables to be compared to the calculations; representations of the solute polarizability; compensation between the loss of hydration enthalpy and gain in Coulomb interactions upon a complex formation; two minima in interaction potentials between polar groups in solution; similarities and dissimilarities between interaction potentials in solution from continuum and molecular theories; continuum calculations of entropies of hydration; and evaluation of a temperature dependence of thermodynamic characteristics of hydration with continuum methods.