Isostructural Levamisole Hydrochloride Ionic Cocrystal Solvates: High Z″ with a Low Melting Point

Yao, Yi-chen; Jin, Zhe; Hong, Minghuang; Zhu, Bin; Ren, Guo-Bin; Qi, Ming-Hui

doi:10.1021/acs.cgd.3c01267

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…Thus, it is very important to pay attention on how to control reasonably well the formation of solvates. Additionally, multicomponent solvates are also applied to improve the API’s physiochemical properties, such as hydration stability, enhanced dissolution, low melting point, and enhanced solubility . Therefore, if the multicomponent solvates are the final solid forms, the investigation of stability and desolvation conditions of the solvates may need important and crucial attention.…”

Section: Introductionmentioning

confidence: 99%

Weak but Vital: The Role of Solvents in Crystal Packing and Coassembly for the Formation of Multicomponent Salt Solvates of Clozapine with Oxalic Acid

Li,

Zhang,

Wang

et al. 2024

Crystal Growth & Design

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In order to explore the role of solvent molecules (acetonitrile and ethanol) in crystal packing and coassembly for the formation of three multicomponent salt solvates of clozapine (CLZ) with oxalic acid (OXA), i.e., CLZ-OXA1 ([CLZ2+]:[HOXA–]:[OXA2–]:acetonitrile = 1:1:0.5:1), CLZ-OXA2 ([CLZ2+]:[HOXA–]:[OXA2–]:ethanol = 1:1:0.5:1), and CLZ-OXA3 ([CLZ+]:[OXA2–]:ethanol = 1:0.5:1), experimental and computational studies via density functional theory and molecular dynamics were employed to relate intermolecular interactions to packing arrangements, formation mechanism, stability, and the desolvation process of CLZ salt solvates. The crystal structures of three CLZ salt solvates were analyzed to show that both weak interactions C–H···X (X = O, N, or π) and van der Waals forces were of great importance in the process of self-assembly as well as strong and conventional hydrogen bonds (N–H···O and O–H···O), leading to a stable and diverse multidimensional supramolecular architecture. The packing arrangement and crystal assembly analysis implied that CLZ-OXA1 and CLZ-OXA2 were isostructural. Furthermore, solvent molecules were classified as isolated sites in the packing cages consisting of CLZ and OXA to fill the vacancies in the framework and compensate for the weak interactions or charges. Particularly, ethanol molecules in CLZ-OXA3 also acted as very important bridge-builders, contributing to the formation of the multicomponent crystals. The thermal analysis results indicated that the solvent molecules cannot easily escape from their sites; however, when desolvation occurred, the CLZ multicomponent crystal structures collapsed immediately, indicating the critical role of solvent molecules in stabilizing the crystal structure via intermolecular interactions. After filling the void space, the relatively more negative lattice energy than pure CLZ and the increased packing coefficients may also be the important driving forces for the solvation formation. The present study might provide an opportunity to further reveal the role of solvent molecules in the solid form of the antipsychotic drug CLZ.

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Section: Introductionmentioning

confidence: 99%

Weak but Vital: The Role of Solvents in Crystal Packing and Coassembly for the Formation of Multicomponent Salt Solvates of Clozapine with Oxalic Acid

Li,

Zhang,

Wang

et al. 2024

Crystal Growth & Design

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Novel Supramolecular Heterosynthons [C–I···N═N] and [C–I···π(C≡C)]

Torubaev,

Skabitsky

2024

Crystal Growth & Design

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Heteromolecular C–I···π(CC) and C–I···(LEP)NN (LEP lone electron pair) have been observed for the first time in cocrystals of diphenylacetylene (tolan, Ph2C2) and azobenzene (Ph2N2) with halogen bond donor, diiodoacetylene (C2I2). Computational analysis (density functional theory (DFT), molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM)) indicates that C–I···π(CC) and C–I···(LEP)NN interactions are stronger than I···π(Ph), which is also possible between iodo-XB donors and Ph2C2 or Ph2N2. However, cocrystallization of Ph2C2 and Ph2N2 with isomeric series of o-, m-, p-diiodotetrafluorobenzenes (1,2-, 1,3-, 1,4-DITFB) and pentafluoroiodobenzene (C6F5I) afforded the cocrystals stabilized predominantly by the relatively weaker I···π(Ph) interactions, while 1,3-DITFB featured both I···π(CC) and I···π(Ph) halogen bonds. Analysis of the interplay of intermolecular interactions and energetic, molecular symmetry, and packing factors in cocrystals revealed a complex structural landscape and suggested the lowering of molecular symmetry to achieve the desired [C–I···π(CC)] and [C–I···(LEP)NN] for diiodotetrafluorobenzene coformers. Besides these promising structural motifs, we discuss here the formation of chiral cocrystal structures from achiral coformers and high-Z′ structure Ph2N2 1,2-DITFB (2:3).

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Isostructural Levamisole Hydrochloride Ionic Cocrystal Solvates: High Z″ with a Low Melting Point

Cited by 2 publications

References 39 publications

Weak but Vital: The Role of Solvents in Crystal Packing and Coassembly for the Formation of Multicomponent Salt Solvates of Clozapine with Oxalic Acid

Weak but Vital: The Role of Solvents in Crystal Packing and Coassembly for the Formation of Multicomponent Salt Solvates of Clozapine with Oxalic Acid

Novel Supramolecular Heterosynthons [C–I···N═N] and [C–I···π(C≡C)]

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