Molecular Insights into Water–Chloride and Water–Water Interactions in the Supramolecular Architecture of Aconine Hydrochloride Dihydrate

Abstract

Despite the previous preparation of aconine hydrochloride monohydrate (AHM), accurate determination of the crystal's composition was hindered by severely disordered water molecules within the crystal. In this study, we successfully prepared a new dihydrate form of the aconine hydrochloride [C 25 H 42 NO 9 + Cl − •2(H 2 O), aconine hydrochloride dihydrate (AHD)] and accurately refined all water molecules within the AHD crystal. Our objective is to elucidate both water−chloride and water−water interactions in the AHD crystal. The crystal structure of AHD was determined at 136 K using X-ray diffraction and a multipolar atom model was constructed by transferring chargedensity parameters to explore the topological features of key short contacts. By comparing the crystal structures of dihydrate and monohydrate forms, we have observed that both AHD and AHM exhibit identical aconine cations, except for variations in the number of water molecules present. In the AHD crystal, chloride anions and water molecules serve as pivotal connecting hubs to establish three-dimensional hydrogen bonding networks and one-dimensional hydrogen bonding chain; both water−chloride and water−water interactions assemble supramolecular architectures. The crystal packing of AHD exhibits a complete reversal in the stacking order compared to AHM, thereby emphasizing distinct disparities between them. Hirshfeld surface analysis reveals that H••• Cl − and H•••O contacts play a significant role in constructing the hydrogen bonding network and chain within these supramolecular architectures. Furthermore, topological analysis and electrostatic interaction energy confirm that both water−chloride and water− water interactions stabilize supramolecular architectures through electrostatic attraction facilitated by H•••Cl − and H•••O contacts. Importantly, these findings are strongly supported by the existing literature evidence. Consequently, navigating these water−chloride and water−water interactions is imperative for ensuring storage and safe processing of this pharmaceutical compound.