Using MD Simulations To Calculate How Solvents Modulate Solubility

Here, our interest is in predicting
solubility in general, and
we focus particularly on predicting how the solubility of particular
solutes is modulated by the solvent environment. Solubility in general
is extremely important, both for theoretical reasons – it provides
an important probe of the balance between solute–solute and
solute–solvent interactions – and for more practical
reasons, such as how to control the solubility of a given solute via
modulation of its environment, as in process chemistry and separations.
Here, we study how the change of solvent affects the solubility of
a given compound. That is, we calculate relative solubilities. We
use MD simulations to calculate relative solubility and compare our
calculated values with experiment as well as with results from several
other methods, SMD and UNIFAC, the latter of which is commonly used
in chemical engineering design. We find that straightforward solubility
calculations based on molecular simulations using a general small-molecule
force field outperform SMD and UNIFAC both in terms of accuracy and
coverage of the relevant chemical space.