Solution Thermodynamics of l-Glutamic Acid Polymorphs from Finite-Sized Molecular Dynamics Simulations

Area of Science:

• Physical Chemistry
• Materials Science
• Computational Chemistry

Background:

• Accurate thermodynamic parameters are crucial for digital design in industrial crystallization.
• Current methods for obtaining these parameters can be computationally intensive.
• Understanding crystal nucleation from solution is key for process optimization.

Purpose of the Study:

• To develop an efficient simulation framework for estimating atomic-scale thermodynamic parameters of crystallization.
• To enable accurate prediction of solubility and surface tension for organic crystals.
• To investigate the relative stability and solubility of polymorphs, using l-glutamic acid as a case study.

Main Methods:

• Utilizing molecular dynamics (MD) simulations based on the thermodynamics of crystal nucleation in confined solutions.
• Estimating solubility and surface tension from a limited number of unbiased MD simulations at a reference temperature.
• Extending results to capture the solubility curve with minimal computational overhead.

Main Results:

• The framework efficiently estimates solubility and surface tension without complex free energy calculations.
• Analysis of l-glutamic acid polymorphs shows good agreement with experimental data for relative stability and solubility.
• Absolute solubility predictions, while not quantitatively perfect with current force fields, demonstrate the method's potential.

Conclusions:

• The developed simulation approach provides an efficient and self-consistent method for obtaining critical thermodynamic data.
• This framework facilitates high-throughput polymorph screening and supports digital design strategies for crystallization.
• The findings pave the way for more accurate computational modeling of crystallization processes.