A deracemization technique using periodic temperature fluctuations on a conglomerate forming system undergoing a swift racemization in solution is demonstrated. The method uses heating and cooling periods of the suspension in order to create cycles of partial dissolution of the crystal phase followed by crystal regrowth: this enables symmetry breaking in the solid phase. The technique is an effective, simple, and cheap operation, and can promote understanding of the effects of dissolution and recrystallization on chiral symmetry breaking in the solid phase. The heating period leads to the decrease of the size of crystals and the destruction of small crystals; the surviving crystals can then grow during the cooling period. A succession of such cycles allows the autocatalytic transformation from a racemic suspension into pure enantiomer, with an enantiomeric excess (ee) > 99% within a few days. The results demonstrate a possible mechanism for the emergence of homochirality of molecules of biological significance on Earth.

Cocrystallization has been promoted as an attractive early development tool as it can change the physicochemical properties of a target compound and possibly enable the purification of single enantiomers from racemic compounds. In general, the identification of adequate cocrystallization candidates (or coformers) is troublesome and hampers the exploration of the solid-state landscape. For this reason, several computational tools have been introduced over the last two decades. In this study, cocrystals of Praziquantel (PZQ), an anthelmintic drug used to treat schistosomiasis, are predicted with network-based link prediction and experimentally explored. Single crystals of 12 experimental cocrystal indications were grown and subjected to a structural analysis with single-crystal X-ray diffraction. This case study illustrates the power of the link-prediction approach and its ability to suggest a diverse set of new coformer candidates for a target compound when starting from only a limited number of known cocrystals.

A cocrystal screening of the chiral drug “proxyphylline” (PXL) and achiral coformers was performed using dry or solvent assisted grinding and evaporation methods, yielding 10 different original solid forms with a 1:1 stoichiometry. Among them, three anhydrous cocrystals and a monohydrated conglomerate forming system have been identified with salicylic acid (SA). The crystal structures of the monohydrate and one of the racemic anhydrous forms were determined by X-ray single crystal experiments. The dehydration mechanism of the hydrate has been investigated by thermal analysis, X-ray powder diffraction, and water sorption–desorption cycles. The importance of water molecules in the crystal structure and the concomitant loss of both water and SA (cocrystal former) during the dehydration suggest a destructive mechanism.