The application of halogen bonding in pharmaceutical chemistry remains a challenge. In this work, novel halogen-bonded cocrystals based on azole antifungal active pharmaceutical ingredients (APIs) and the ditopic molecule 1,4-diiodotetrafluorobenzene are reported. Their crystal structural features, spectroscopic properties, and thermal stability were studied. The components are bound through I···N from the triazole moieties present in all of the compounds.
The molecular electrostatic potential (MEP) surfaces and quantum theory of atoms in molecules (QTAIM) calculations are used to rationalize the presence of hydrogen and halogen bonds in the resulting structures and their energetic analysis. The relative halogen bond ability of the different groups of voriconazole, fluconazole, and itraconazole was analyzed using MEP surfaces, demonstrating this approach to be an interesting tool to predict halogen-bonding preferences.