Two polymorphs of the drug compound metergoline (C₂₅H₂₉N₃O₂) were investigated in detail by solid-state NMR measurements. The results have been analysed by an advanced procedure, which uses experimental input together with the results of quantum chemical calculations that were performed for molecular crystals. In this way, it was possible to assign the total of 40 ¹H–¹³C correlation pairs in a highly complex system, namely, in the dynamically disordered polymorph with two independent molecules in the unit cell of a large volume of 4234 ų. For the simpler polymorph, which exhibits only small-amplitude motions and has just one molecule in the unit cell with a volume of 529.0 ų, the values of the principal elements of the ¹³C chemical shift tensors were measured. Additionally, for this polymorph, a set of crystal structure predictions were generated, and the {¹³C, ¹H} isotropic and ¹³C anisotropic chemical shielding data were computed while using the gauge-including projector augmented-wave approach combined with the “revised Perdew-Burke-Ernzerhof“ exchange-correlation functional (GIPAW-RPBE). The experimental and theoretical results were combined in an application of the newly developed strategy to polymorph discrimination. This research thus opens up new routes towards more accurate characterization of the polymorphism of drug formulations.

The benzene dimer (BD) is an archetypal model of π∙∙∙π and C–H∙∙∙π noncovalent interactions as they occur in its cofacial and perpendicular arrangements, respectively. The enthalpic stabilization of the related BD structures has been debated for a long time and is revisited here. The revisit is based on results of computations that apply the coupled-cluster theory with singles, doubles and perturbative triples [CCSD(T)] together with large basis sets and extrapolate results to the complete basis set (CBS) limit in order to accurately characterize the three most important stationary points of the intermolecular interaction energy (ΔE) surface of the BD, which correspond to the tilted T-shaped (TT), fully symmetric T-shaped (FT) and slipped-parallel (SP) structures. In the optimal geometries obtained by searching extensive sets of the CCSD(T)/CBS ΔE data of the TT, FT and SP arrangements, the resulting ΔE values were −11.84, −11.34 and −11.21 kJ/mol, respectively. The intrinsic strength of the intermolecular bonding in these configurations was evaluated by analyzing the distance dependence of the CCSD(T)/CBS ΔE data over wide ranges of intermonomer separations. In this way, regions of the relative distances that favor BD structures with either π∙∙∙π or C–H∙∙∙π interactions were found and discussed in a broader context.

Anisotropy and local dynamics of crystalline biogenic carboxylic acids are investigated using NMR-crystallography. Calorimetry is employed to determine phase behavior. All experimental observations are interpreted in terms of ab initio calculations.