Multicomponent organic crystals at high pressure

Abstract

High-pressure research of the crystals of organic and coordination compounds is now a well-established field. However, the studies of multicomponent crystals (hydrates, solvates, salts and co-crystals) are just emerging. The aim of this paper is to give a personal view of what makes the multicomponent organic systems peculiar for high-pressure research as compared with the monocomponent ones. Several different types of structure response to compression and reverse decompression are reviewed with examples based on research of salts, co-crystals and hydrates of amino acids. Challenges and prospects of further studies are discussed.

Effect of High Pressure on the Crystal Structures of Polymorphs of l-Histidine

“…A gradual phase transition to the -form was observed between 3.63 GPa and 4.24 GPa. The bulk moduli of the -form obtained from the experiment and the calculations were found to be in very good agreement, being respectively 11.8 (5) and 12.5(2) GPa. A similar study performed using single-crystal X-ray diffraction found a bulk modulus of 10.1 (7) GPa.…”

Direct and Inverse Relations between Temperature and Pressure Effects in Crystals: A Case Study on o-Xylene

“…Their collapse induces a transition, and a new phase of benzene is formed . Thus, the compression of crystals can change the preferred intermolecular interactions and can cause molecular rearrangements, multicomponent crystallization, and phase transitions. − Presently we have investigated the effect of pressure and temperature on another molecular crystal of an aromatic compound; o- xylene (1,2-dimethylbenzene, melting point (m.p.) = 248 K, Figure ) is liquid at normal conditions, due to the absence of cohesion forces stronger than hydrogen bonds C–H···π.…”

Hydrate vs Anhydrate under a Pressure-(De)stabilizing Effect of the Presence of Water in Solid Forms of Sulfamethoxazole

“…38,39 Similarly to the solubility, the pressure stability of a drug substance can be modified (increased or decreased) by introducing foreign molecules or ions into the crystal structure and formation of multicomponent crystals. 40 The destabilizing effect of a second component was observed for glycine and its cocrystal with glutaric acid, 41 as well as for DL-alanine and DLalaninium semioxalate monohydrate, 42 where the introduction of the second component led to the disruption of homosynthones. On the other hand, cocrystallization of DL-cysteine with oxalic acid, 43 leading to the transformation of the amino acid into a cation, improved the pressure stability of the crystal.…”

“…However, it is worth noting that during the tableting process via compaction of APIs can also be subjected to nonambient pressure, a stimulus known to efficiently affect the crystal structure. Exposing crystals to high pressure can lead to solid-state phase transitions, , crystal amorphization, chemical reactions in the solid state, or even pressure-induced solvation. , In rare cases pressure has even led to an increase in the solubility of the investigated crystals. , Therefore, pressure can be a powerful tool used in the search of new crystal forms of the APIs, but it also should be considered in the study of their stability to avoid unintentional solid-state transformations during the tablet manufacturing process. , Similarly to the solubility, the pressure stability of a drug substance can be modified (increased or decreased) by introducing foreign molecules or ions into the crystal structure and formation of multicomponent crystals . The destabilizing effect of a second component was observed for glycine and its cocrystal with glutaric acid, as well as for dl -alanine and dl -alaninium semioxalate monohydrate, where the introduction of the second component led to the disruption of homosynthones.…”