a. Department of Chemistry, University of Bologna, Via Zamboni 33, Bologna 40126, Italy

b. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

The enantiomers of a previously reported naphthalimide derivative are shown in this study to form a solid solution; furthermore, on the basis of the knowledge of solid solution structural aspects other naphthalimide derivatives have been synthesized and shown to lack the enantioselectivity in the solid state. The structural origin of solid solution formation is the same as observed in most of the cases in the literature—quasi-centrosymmetric structures form at nonracemic compositions where the most abundant enantiomer adjusts its conformation to mimic the absent one. Such solid solutions belong to the type showing some enantioselectivity. An extended single crystal X-ray diffraction study of the crystals of different enantiomeric compositions reveals the nature of the disorder in studied solid solutions. Intermolecular interactions are analyzed in terms of Hirshfeld surfaces and by means of density functional theory calculations to explore the differences of isostructural quasi-centrosymmetric (enantiopure) and genuine centrosymmetric (racemic) packings to shed light on the energetic aspects of solid solution formation as well as to explain the origin of partial enantioselectivity. Furthermore, lattice energy calculations explain why two structurally distinct solid solutions (around the racemic and near the pure enantiomer regions) form as found for one of the studied compounds.

a. Faculty of Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

Solvate formation and the desolvation mechanism of 25 obtained methyl cholate solvates were rationalized using crystal structure analysis and study of the phase transformations. The facile solvate formation was determined to be associated with the possibility for more efficient packing in structures containing solvent molecules. Most of the obtained solvates crystallized in one of the six isostructural solvate groups, with solvent selection based on the solvent capability to provide particular intermolecular interactions along with appropriate size and shape. In crystal structures several different methyl cholate conformers were observed, as apparently more efficient packing could be achieved by diversifying the molecule conformation and even adopting energetically quite unfavorable conformations. Nevertheless, the packing was generally controlled by the steroid ring system, particularly employing hydrogen bonding of the attached hydroxyl groups. Study of the desolvation mechanism showed that the primary desolvation product is determined by the structure similarity with the solvate, with thermodynamic stability of the desolvate having no directly identifiable effect. In the case of the absence of an acceptable structurally similar desolvate, desolvation produced an amorphous phase.

a. Faculty of Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

Study of structures and physicochemical properties of racemic (rac-H) and enantiopure (enant-H) hydrates of the active pharmaceutical ingredient pimobendan revealed that both hydrates have highly similar crystal structures and exhibit unusually high stability. Both structures contain identical two-dimensional layers and very similar conformations. The most significant difference is the stacking of these layers. The high stability of both hydrates appeared as extremely low solubility over a wide temperature range as well as an exceptionally high dehydration temperature and melting point. Study of the dehydration process showed that both hydrates have different activation energies of dehydration and kinetic model. Intermolecular interaction energy calculations showed that the dispersion interactions provide a highly significant stabilizing force in both pimobendan hydrates, while their exceptionally high stability can be associated with an efficient interplay between the hydrogen bonding and the dispersion interactions.

a. Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstraße 1, 39106 Magdeburg, Germany

b. Faculty of Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

c. Institute of Organic Chemistry, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest 1004, Hungary

A detailed thermochemical and structural study of the phenylpiracetam enantiomer system was performed by characterizing the solid solutions, rationalizing the structural driving force for their formation as well as identifying a common structural origin responsible for the formation of solid solutions of enantiomers. Enantiomerically pure phenylpiracetam forms two enantiotropically related polymorphs (enant–A and enant–B). Transition point (70(7) °C) was determined based on isobaric heat capacity measurements. Structural studies revealed that enant–A and enant–B crystallize in space groups P1 (Z'=4) and P212121 (Z'=2), respectively. However, pseudoinversion centres were present resulting in apparent centrosymmetric structures. The quasi–centrosymmetry was achieved by a large variety of phenylpiracetam conformations in the solid state (6 in total). As a result, miscibility of the phenylpiracetam enantiomers in the solid state is present for scalemic and racemic samples, which was confirmed by the melt phase diagram. Racemic phenylpiracetam (rac–A) was determined to crystallize in P–1 space group being isostructural to enant–A, furthermore, disorder is present showing that enantiomers are distributed in a random manner. The lack of enantioselectivity in the solid state is explained. Furthermore, structural aspects of phenylpiracetam solid solutions are discussed in the scope of other cases reported in the literature.

a. Faculty of Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

In this study, detailed analysis of crystal structures was used to rationalize the observed stability and phase transformations of sequifenadine hydrochloride polymorphs and hydrates, as well as to understand the observed structural diversity. The performed polymorph and hydrate screening revealed the existence of six polymorphs and four hydrates. Crystal structures of these phases were determined either from single crystal or from powder diffraction data. The different possibilities for packing of sequifenadine cations were found to be the main reason for the observed structural diversity of polymorphs. The hydrate structures were found to be structurally similar and related to those of particular polymorphs, which was consistent with the observed easy phase transitions amongst the related pairs.