Universal Solvation Model Based on Solute Electron Density and a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions

Marenich, A. V.; Cramer, C. J.; Truhlar, D. G.

*J. Phys. Chem. B*
**2009**, *113*, 6378.

We present a new continuum solvation model based on the quantum mechanical
charge density of a solute molecule interacting with continuum description
of the solvent. The model is called SMD, where the "D" stands for "density"
to denote that the full solute electron density is used without defining
partial atomic charges. "Continuum" denotes that the solvent is not
represented explicitly but rather as a dielectric medium with surface
tension at the solute-solvent boundary. SMD is a universal solvation model,
where "universal" denotes its applicability to any charged or uncharged
solute in any solvent or liquid medium for which a few key descriptors are
known (in particular dielectric constant, refractive index, bulk surface
tension, and acidity and basicity parameters). The model separates the
observable solvation free energy into two main components. The first
component is the bulk electrostatic contribution arising from a
self-consistent reaction field treatment that involves the solution of the
nonhomogeneous Poisson equation for electrostatics in terms of the
Integral-Equation-Formalism Polarizable Continuum Model (IEF-PCM). The
cavities for the bulk electrostatic calculation are defined by
superpositions of nuclear-centered spheres. The second component is called
the cavity-dispersion-solvent-structure term and is the contribution
arising from short-range interactions between the solute and solvent
molecules in the first solvation shell. This contribution is a sum of terms
that are proportional (with geometry-dependent proportionality constants
called atomic surface tensions) to the solvent-accessible surface areas of
the individual atoms of the solute. The SMD model has been parameterized
with a training set of 2821 solvation data including 112 aqueous ionic
solvation free energies, 220 solvation free energies for 166 ions in
acetonitrile, methanol, and dimethyl sulfoxide, 2346 solvation free
energies for 318 neutral solutes in 91 solvents (90 nonaqueous organic
solvents and water), and 143 transfer free energies for 93 neutral solutes
between water and 15 organic solvents. The elements present in the solutes
are H, C, N, O, F, Si, P, S, Cl, and Br. The SMD model employs a single set
of parameters (intrinsic atomic Coulomb radii and atomic surface tension
coefficients) optimized over six electronic structure methods:
M05-2X/MIDI!6D, M05-2X/6-31G*, M05-2X/6-31+G**, M05-2X/cc-pVTZ,
B3LYP/6-31G*, and HF/6-31G*. Although the SMD model has been parameterized
using the IEF-PCM protocol for bulk electrostatics, it may also be employed
with other algorithms for solving the nonhomogeneous Poisson equation for
continuum solvation calculations in which the solute is represented by its
electron density in real space. This includes, for example, the
conductor-like screening algorithm. With the 6-31G* basis set, the SMD
model achieves mean unsigned errors of 0.6-1.0 kcal/mol in the solvation
free energies of tested neutrals and mean unsigned errors of 4 kcal/mol on
average for ions with either *Gaussian03* or *GAMESS*.