Halogen-bonded cocrystallization of racetam pharmaceuticals and perfluorinated iodobenzenes†

In this work, four novel halogen-bonded cocrystals of three racetam-family pharmaceutical compounds, named etiracetam, aniracetam and nefiracetam, were prepared using perfluorinated iodobenzenes as halogen bond donors through both mechanochemical and solution crystallization methods. The cocrystals were characterized by powder X-ray diffraction and single crystal X-ray diffraction. Structural analysis revealed that in all of the obtained cocrystals, the most prominent supramolecular interaction is the I⋯O_carbonyl halogen bond. In all cocrystals, the donors are ditopic, while additionally forming an I⋯π halogen bond in the cocrystal of (NEFI)(DITF). In order to rank the acceptor sites, molecular electrostatic potentials of racetam pharmaceutical compounds were calculated on their optimized geometries. Furthermore, Hirshfeld surface analysis was performed to explore the intermolecular interactions in detail. These calculations were consistent with experimental observations, providing a comprehensive understanding of the cocrystal structures and intermolecular forces.