Polymorphism and solid state peculiarities in imidazo[1,5-a]pyridine core deriving compounds: An analysis of energetic and structural driving forces

The polymorphism and solid-state peculiarities of imidazo[1,5-a]pyridine derivatives have been investigated by a theoretical and experimental approach to shed light on the structural and energetic features. Four couples of polymorphs and an ionic crystal form have been reported and analysed. Hirshfeld Surface and Energy Frameworks have been used to better understand the crystal packing features, in comparison with literature structures. The collection of these characterizations made possible to analyze the differences between the polymorphs, the energetic components dominating the crystal packing, and the effect of the different substitutions on the central molecular skeleton on packing disposition. To complete the solid state characterization of the molecular products, the assignment of vibrational spectra for the imidazo[1,5-a]pyridine core derivatives has been performed for the first time and the influence of substituents commented. Although the discussed polymorphs are very different in their crystal packing, from the energetic point of view they present a strong similarity. In all cases, the main interactions are π‧‧‧π stacking and C-H‧‧‧π to the aromatic rings, with some tendency to the formation of C-H‧‧‧N contacts to the central imidazo[1,5-a]pyridine nitrogen. The main energetic component is the dispersive one, with some contribution from the electrostatic component, and this situation is not modified by the presence of differing substituents. When hydrogen bond are present, the crystal packing is strongly modified and, energetically, the electrostatic component can overcome the dispersive one.