Study on four polymorphs of bifendate based on X-ray crystallography

Area of Science:

• Solid-state chemistry
• Crystallography
• Pharmaceutical science

Background:

• Bifendate, an anti-hepatitis drug, is known to exist in multiple crystalline forms (polymorphs).
• Two polymorphs (A and B) of bifendate have been previously reported.

Purpose of the Study:

• To obtain and characterize new crystallosolvates of bifendate.
• To investigate the molecular conformation, intermolecular interactions, and crystal packing of bifendate polymorphs.
• To elucidate the fundamental basis for bifendate polymorphism.

Main Methods:

• Single-crystal X-ray crystallography was used to determine the structures of four crystalline forms.
• Thermal analysis and Fourier transform infrared (FT-IR) spectroscopy were employed for characterization.
• Simulated powder X-ray diffraction (PXRD) patterns were calculated from single-crystal data.

Main Results:

• Three new bifendate crystallosolvates with tetrahydrofuran, dioxane, and pyridine were successfully obtained.
• Differences in molecular conformation, intermolecular interactions, and crystal packing were identified among the four forms.
• Guest solvent molecules intercalated into host molecule channels via aromatic stacking or hydrogen bonds, influenced by solvent volume and planarity.
• Solvent-augmented rotation of the biphenyl group's C-C bond significantly impacted host conformation and contributed to polymorphism.
• Unique simulated PXRD patterns were generated for each crystalline form.

Conclusions:

• The study successfully characterized four crystalline forms of bifendate, including three novel crystallosolvates.
• The findings provide insights into the structural basis of bifendate polymorphism, driven by conformational changes and solvent interactions.
• Understanding these polymorphs is crucial for the development and formulation of bifendate as an anti-hepatitis therapeutic.