The two major polymorphs of the active pharmaceutical ingredient indomethacin were studied using a combination of experimental low-frequency vibrational spectroscopies, theoretical solid-state density functional theory and ab initio molecular dynamics calculations. The results enable a complete spectral assignment of the low-frequency IR and Raman spectra, and yield new insight into the energetic and dynamical factors present within the solids to be understood. Ultimately, these results are used to rationalize the thermodynamic properties of the two crystals, which result in a contradiction to the long-held belief that the -form is the more stable polymorph at ambient conditions due to its predominant abundance. Overall, the study highlights the combined role that molecular conformation, bulk packing arrangement, and intermolecular forces have on the ultimate properties of pharmaceutical crystals, and the need for detailed analyses into all of these effects in order to predict the properties of materials.

A single lattice vibration at 15.5 cm−1 serves as a gateway for the polymorphic conversion of thermosalient 1,2,4,5-tetrabromobenzene crystals.

In ZIF-8 and its cobalt analogue ZIF-67, the imidazolate methyl-groups, which point directly into the void space, have been shown to freely rotate - even down to cryogenic temperatures. Using a combination of experimental terahertz time-domain spectroscopy, low-frequency Raman spectroscopy, and state-of-the-art ab initio simulations, the methyl-rotor dynamics in ZIF-8 and ZIF-67 are fully characterized within the context of a quantum-mechanical hindered-rotor model. The results lend insight into the fundamental origins of the experimentally observed methyl-rotor dynamics, and provide valuable insight into the nature of the weak interactions present within this important class of materials.