Experimental Electron Density Distribution in Two Cocrystals of Betaines with p-Hydroxybenzoic Acid

Abstract

Experimental determination of electron density distribution in crystals by means of high-resolution X-ray diffraction allows, among others, for studying the details of intraand inter-molecular interactions. In case of co-crystals, this method may help in finding the conditions of creating such species. The results of such analysis for two co-crystals containing betaines, namely trigonelline (TRG: nicotinic acid N-methylbetaine, IUPAC name: 1-methylpyridinium-3-carboxylate) and N-methylpiperidine betaine (MPB: 1-methylpiperidinium-1yl-carboxylate) with p-hydroxybenzoic acid (HBA) are reported. TRG-HBA crystallizes as a hydrate. For both of the co-crystals, high-quality diffraction data were collected up to sinθ/λ = 1.13 Å −1. Hansen-Coppens multipolar model was then applied for modelling the electron density distribution and Atoms-In-Molecules approach was used for detailed analysis of interactions in crystals. A number of intermolecular interactions was identified, ranging from strong O-H•••O hydrogen bonds through C-H•••O to C-H•••π and π•••π interactions. Correlations between the geometrical characteristics of the contacts and the features of their critical points were analyzed in detail. Atomic charges show that in zwitterionic species there are regions of opposite charges, rather than charges that are localized on certain atoms. In case of MPB-HBA, a significant charge transfer between the components of co-crystal (0.5 e) was found, as opposed to TRG-HBA, where all of the components are almost neutral.

Crystal engineering of a co-crystal of antipyrine and 2-chlorobenzoic acid: relative energetic contributions based on multipolar refinement

“…The reason for this scarcity is the inherently weak diffraction by the cocrystals. An exhaustive literature survey provides the experimental electron-density analyses 42 of only a few co-crystals namely piroxicam–saccharin, 43 betaines- p -hydroxybenzoic acid, 44 melamine-barbital, 45 isonicotinamide-monofluorobenzoic acids, 46 nicotinamide-salicylic acid; nicotinamide-oxalic acid, 47 8-hydroxyquinoline-salicylic acid, 48 sulfamethizole-oxalates/sulphates, 49 to have been successfully analysed, highlighting the challenges and importance of electron-density in better understanding of intermolecular interactions in crystalline solids. 50,51 In all of the above mentioned studies, the role of weak intermolecular interactions has been emphasized through a topological analysis highlighting their importance in stabilizing the cocrystal systems.…”