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Published on: June 7, 2018
X-Ray Diffraction and Theoretical Calculation-Supported Formation of Polymorphic Cocrystals Discovered Through
Zhengzheng Zhou1, Mónica Calatayud2, Julia Contreras-García2
1Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China.
Journal of Pharmaceutical Sciences
|May 31, 2019
Summary
Researchers discovered new polymorphic cocrystals of salicylic acid and 3-nitrobenzamide using thermal analysis. This method provides a simple and reliable way to find these important pharmaceutical compounds and understand their formation.
Area of Science:
- Materials Science
- Crystallography
- Physical Chemistry
Background:
- Cocrystal polymorphism is prevalent and significant in pharmaceuticals.
- Discovering polymorphic cocrystals and their formation mechanisms remains challenging.
Purpose of the Study:
- To report the novel discovery of salicylic acid: 3-nitrobenzamide (SA-3NBZ) polymorphic cocrystals.
- To elucidate the formation mechanism of these polymorphic cocrystals.
- To validate thermal analysis as a method for discovering polymorphic cocrystals.
Main Methods:
- Differential scanning calorimetry (DSC) and hot stage microscopy (HSM) for cocrystal discovery.
- Single-crystal X-ray diffraction (SCXRD) for structural confirmation.
- Density functional theory (DFT) calculations for mechanism elucidation and energetic analysis.
Main Results:
- Novel SA-3NBZ polymorphic cocrystals with 1:1 and 2:2 molar ratios were successfully discovered.
- SCXRD confirmed the formation of these cocrystals.
- DFT calculations indicated weak energetic stabilization (-0.01 to -0.05 eV/molecule) attributed to hydrogen bonds and van der Waals forces.
Conclusions:
- Thermal analysis (DSC/HSM) is a simple, reliable, and effective method for discovering polymorphic cocrystals.
- The study provides insights into the formation mechanism of SA-3NBZ polymorphic cocrystals.
- The findings contribute to the understanding and discovery of cocrystal polymorphism in materials science.
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