Force Field Benchmark of Organic Liquids. 2. Gibbs Energy of Solvation

Quantitative
prediction of physical properties of liquids is a longstanding goal
of molecular simulation. Here, we evaluate the predictive power of
the Generalized Amber Force Field (Wang et al. J. Comput.
Chem. 2004, 25, 1157–1174)
for the Gibbs energy of solvation of organic molecules in organic
solvents using the thermodynamics integration (TI) method. The results
are compared to experimental data, to a model based on quantitative
structure property relations (QSPR), and to the conductor-like screening
models for realistic solvation (COSMO-RS) model. Although the TI calculations
yield slightly better correlation to experimental results than the
other models, in all fairness we should conclude that the difference
between the models is minor since both QSPR and COSMO-RS yield a slightly
lower RMSD from that of the experiment (<3.5 kJ/mol). By analyzing
which molecules (either as solvents or solutes) are outliers in the
TI calculations, we can pinpoint where additional parametrization
efforts are needed. For the force field based TI calculations, deviations
from the experiment occur in particular when compounds containing
nitro or ester groups are solvated into other liquids, suggesting
that the interaction between these groups and solvents may be too
strong. In the COSMO-RS calculations, outliers mainly occur when compounds
containing (in particular aromatic) rings are solvated despite using
a ring correction term in the calculations.