A streamlined molecular-dynamics workflow for computing solubilities of molecular and ionic crystals.

Area of Science:

• Computational chemistry
• Materials science
• Chemical engineering

Background:

• Calculating crystal solubility via atomistic simulations is difficult due to complex free-energy methods and slow equilibration.
• Existing methods for solubility computation present convergence challenges and require significant computational resources.

Purpose of the Study:

• To introduce a simplified and robust molecular-dynamics workflow for computing the solubility of molecular or ionic crystals.
• To streamline and optimize the process of solubility calculation, making it more accessible and efficient than current state-of-the-art methods.

Main Methods:

• A novel molecular-dynamics workflow is presented, calculating the crystal's chemical potential using a gas-phase molecule as a reference state.
• The S0 method is employed to determine the concentration dependence of the solute's chemical potential.
• The workflow was validated by predicting the solubilities of sodium chloride, urea polymorphs, and paracetamol polymorphs in various solvents.

Main Results:

• The developed workflow provides a more straightforward and robust method for crystal solubility computation.
• Predicted solubility is sensitive to the chosen potential energy surface.
• The harmonic approximation was found to be inadequate for molecular crystals and gas molecules at or above room temperature.

Conclusions:

• The new workflow offers a significant improvement in the ease and robustness of crystal solubility calculations.
• The study highlights the importance of the potential energy surface and the limitations of the harmonic approximation in solubility predictions.
• The assumption of an ideal solution may not hold for highly soluble substances, requiring careful consideration in simulations.