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Updated: Jun 13, 2026

Optimization of Crystal Growth for Neutron Macromolecular Crystallography
Published on: March 13, 2021
Thermodynamics and Crystallization Behavior of Meropenem Influenced by Solvent Composition and pH
Jinshen Ren1, Sanli Yin1, Yifu Zhang1
1National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
None:
To develop an improved crystallization process for meropenem trihydrate, an important carbapenem antibiotic, the pH-dependent solubility of meropenem trihydrate in different solvent systems was investigated using the laser monitoring dynamic method. The solubility data displayed a characteristic U-shaped profile. The solvent composition could also affect the solubility data and the isoelectric point of meropenem. The experimental solubility data were well correlated with the Tsuji model. Hirshfeld surface (HS) analysis highlighted the significance of O···H/H···O interactions in the crystal structure. Molecular electrostatic potential surfaces (MEPs) revealed complementary positive and negative regions on the meropenem molecule, enabling solute-solute aggregation through electrostatic interactions. Furthermore, molecular dynamics (MD) simulations provided deeper insights into the influence of ethanol and acetone on the solvation layer of meropenem. Additionally, the effects of pH value and solvent composition on the crystallization process of meropenem trihydrate were discussed. The crystal habit is affected by variations in solvent composition and pH. Finally, the combined effects of solvent polarity, dielectric constant, and solvation on both solubility and the crystallization process were comprehensively summarized.
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