Efficient
Estimation of the Equilibrium Solution-Phase
Fugacity of Soluble Nonelectrolyte Solids in Binary Solvents by Molecular
Simulation
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Abstract
We
present an efficient means to estimate the concentration-dependent
solution-phase fugacity of soluble nonelectrolyte solids in binary
solvents by molecular simulation. The underlying assumption of the
proposed method is that the solute does not associate or interact
with other solute molecules in solution. Solute–solvent and
solvent–solvent interactions are taken into account by calculation
of the solute solution-phase fugacity at infinite dilution by molecular
simulation, and the concentration dependence of the fugacity is taken
into account analytically by a combinatorial activity coefficient
model. The required simulation data can be computed using any conventional
free energy calculation methodology available in many open-source
simulation software packages. Moreover, with knowledge of the fugacity
of the solid phase, the equilibrium solubility can be calculated.
The method has advantages over empirical descriptor-based methods
in that the molecular simulations enable insight into the underlying
driving forces of the process and do not require extensive parametrization
against experimental data. Results are presented for acetaminophen
in binary aqueous solvents of water/acetone and water/2-propanol.
For both solvent systems, we compare five solute force fields, giving
insight into force field selection to yield accurate predictions.
Also, predictions are made using the UNIFAC group-contribution method
and the state-of-the-art 2005 revised MOSCED model, demonstrating
that the accuracy of molecular simulation can be comparable to that
of conventional methods for predictive purposes