Molecular conformation and crystallization: The case of ethenzamide

Ethenzamide is a small, conformationally labile pharmaceutical molecule which crystallizes in an unusual conformation relative to both its co-crystals and to similar molecules found in the Cambridge Structural Database. Relative to its co-crystals, large ethenzamide crystals are challenging to grow, a property which may be linked to the crystal structure conformation. We have explored this link through computational and spectroscopic techniques, studying the conformational properties of the individual molecules in vacuo and in solution. Structures built from alternative conformations have been generated theoretically, but crystallizations under a wide range of conditions have resulted in no new polymorph, though single crystal structures for the known form and two new co-crystals have been solved.