Solid-state-trapped reactive ammonium carbamate self-derivative salts of prolinamide

Single crystals for two polymorphs of the ammonium carbamate self-derivative salt of prolinamide have been successfully obtained and characterized. Decarbonation of the carbamate salts was monitored by calorimetry, confirming stabilization of the reactive carbonated adducts in the solid state. Sublimation of the salts afforded crystals of prolinamide, leading to the first crystal structure of this otherwise common molecule. Reactivity of the ammonium carbamate self-derivative salt is further illustrated by the observation of a series of derived products, including dehydroprolinamide, a methylene-bridged prolinamide, and a bicyclic derivative. Crystal structures of these products display distinct amidic and/or non-amidic hydrogen bonding. This study emphasizes the reactivity of carbonated amines stabilized in the solid and opens perspectives for a systematic study of (solid-state) reactions involving these trapped reactive species

On the influence of using a zwitterionic coformer for cocrystallization: Structural focus on naproxen - proline cocrystals

Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents

Structural study of piracetam polymorphs and cocrystals: crystallography redetermination and quantum mechanics calculations

International audiencePharmaceutical compounds are mostly developed as solid dosage forms containing a single-crystal form. It means that the selection of a particular crystal state for a given molecule is an important step for further clinical outlooks. In this context, piracetam, a pharmaceutical molecule known since the sixties for its nootropic properties, is considered in the present work. This molecule is analyzed using several experimental and theoretical approaches. First, the conformational space of the molecule has been systematically explored by performing a quantum mechanics scan of the two most relevant dihedral angles of the lateral chain. The predicted stable conformations have been compared to all the reported experimental geometries retrieved from the Cambridge Structural Database (CSD) covering polymorphs and cocrystals structures. In parallel, different batches of powders have been recrystallized. Under specific conditions, single crystals of polymorph (III) of piracetam have been obtained, an outcome confirmed by crystallographic analysis