Insights into Intermolecular Interactions of Spironolactone Solvates

To gain insights into the effect of weak interactions in solvate formation and structure–property correlation, experimental (thermal and structural analysis) and computational (lattice and pairwise energy calculations) studies were undertaken to relate intermolecular interactions to packing arrangements, formation mechanism, stability, and the desolvation process of spironolactone (SPI) solvates. Herein, four novel solvates were found, and the crystal structures of five solvates (formic acid, acetic acid, benzene, toluene, and acetonitrile) were resolved for the first time. Structural similarity and diversity of SPI forms are apparent according to the crystal structures, where the strongest interaction is the stacking of the steroid ring system via van der Waals forces. Although the solvent molecules are located in channels (acetonitrile molecules in isolated sites), they form hydrogen bonds and/or dispersion interactions with SPI frameworks. These findings can rationalize the relatively superior stability of SPI solvates. Both increased packing coefficient and additional SPI···solvent interactions are the important driving forces for solvate formation, especially for the van der Waals force controlled solvates. Besides, the thermodynamic stability determines the desolvation of SPI solvates to form II, while the desolvation pattern between formic acid solvate to form I is guided by the isostructural pairs.