TY - JOUR
T1 - Solubility of Organic Salts in Solvent–Antisolvent Mixtures: A Combined Experimental and Molecular Dynamics Simulations Approach
AU - Bjelobrk, Zoran
AU - Rajagopalan, Ashwin Kumar
AU - Mendels, Dan
AU - Karmakar, Tarak
AU - Parrinello, Michele
AU - Mazzotti, Marco
N1 - Funding Information:
Z.B. and M.M. are thankful to Novartis Pharma AG for their partial financial support to this project. Z.B., A.K.R., and M.M. thank Bianca Popa, Ayoung Song, Johann Bartenstein, and Luca Bosetti for performing parts of the experiments. Z.B. thanks Riccardo Capelli for providing the force field for propan-1-ol and Pablo Piaggi, Ruben Wälchli, Thilo Weber, Philipp Müller, and Marco Holzer for valuable discussions. The computational resources were provided by ETH Zürich and the Swiss Center for Scientific Computing at the Euler Cluster.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/8/9
Y1 - 2022/8/9
N2 - We combine molecular dynamics simulations with experiments to estimate solubilities of an organic salt in complex growth environments. We predict the solubility by simulations of the growth and dissolution of ions at the crystal surface kink sites at different solution concentrations. Thereby, the solubility is identified as the solution's salt concentration, where the energy of the ion pair dissolved in solution equals the energy of the ion pair crystallized at the kink sites. The simulation methodology is demonstrated for the case of anhydrous sodium acetate crystallized from various solvent-antisolvent mixtures. To validate the predicted solubilities, we have measured the solubilities of sodium acetate in-house, using an experimental setup and measurement protocol that guarantees moisture-free conditions, which is key for a hygroscopic compound like sodium acetate. We observe excellent agreement between the experimental and the computationally evaluated solubilities for sodium acetate in different solvent-antisolvent mixtures. Given the agreement and the rich data the simulations produce, we can use them to complement experimental tasks, which in turn will reduce time and capital in the design of complicated industrial crystallization processes of organic salts.
AB - We combine molecular dynamics simulations with experiments to estimate solubilities of an organic salt in complex growth environments. We predict the solubility by simulations of the growth and dissolution of ions at the crystal surface kink sites at different solution concentrations. Thereby, the solubility is identified as the solution's salt concentration, where the energy of the ion pair dissolved in solution equals the energy of the ion pair crystallized at the kink sites. The simulation methodology is demonstrated for the case of anhydrous sodium acetate crystallized from various solvent-antisolvent mixtures. To validate the predicted solubilities, we have measured the solubilities of sodium acetate in-house, using an experimental setup and measurement protocol that guarantees moisture-free conditions, which is key for a hygroscopic compound like sodium acetate. We observe excellent agreement between the experimental and the computationally evaluated solubilities for sodium acetate in different solvent-antisolvent mixtures. Given the agreement and the rich data the simulations produce, we can use them to complement experimental tasks, which in turn will reduce time and capital in the design of complicated industrial crystallization processes of organic salts.
U2 - 10.1021/acs.jctc.2c00304
DO - 10.1021/acs.jctc.2c00304
M3 - Article
C2 - 35833664
SN - 1549-9618
VL - 18
SP - 4952
EP - 4959
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 8
ER -