Microscopic Structure and Solubility Predictions of Multifunctional Solids in Supercritical Carbon Dioxide: A Molecular Simulation Study

Molecular
dynamics simulations were employed to both estimate the
solubility of nonelectrolyte solids, such as acetanilide, acetaminophen,
phenacetin, methylparaben, and lidocaine, in supercritical carbon
dioxide and understand the underlying molecular-level driving forces.
The solubility calculations involve the estimation of the solute’s
limiting activity coefficient, which may be computed using conventional
staged free-energy calculations. For the case of lidocaine, wherein
the infinite dilution approximation is not appropriate, we demonstrate
how the activity coefficient at finite concentrations may be estimated
without additional effort using the dilute solution approximation
and how this may be used to further understand the solvation process.
Combining with experimental pure-solid properties, namely, the normal
melting point and enthalpy of fusion, solubilities were estimated.
The results are in good quantitative agreement with available experimental
data, suggesting that molecular simulations may be a powerful tool
for understanding supercritical processes and the design of carbon
dioxide-philic molecular systems. Structural analyses were performed
to shed light on the microscopic details of the solvation of different
functional groups by carbon dioxide and the observed solubility trends.