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Isostructural crystals are crucial for the development of high-performance functional materials and precise control over physicochemical properties, whereas the design of isostructural crystals is extremely challenging. In this work single-component isostructural crystals were obtained with the substitution of side-chain groups. High-quality single crystals of isostructural crystals methyl 2-amino-5-methylbenzoate (MAMB) and methyl 2-amino-5-methoxybenzoate (MAMOB) were harvested through sublimation crystallization. Their crystal structures were determined by single-crystal X-ray diffraction (SCXRD). Similar intermolecular interactions and packing modes suggested that MAMB and MAMOB are 3D isostructural, and the quantitative similarity parameters were calculated via the XPac program. Furthermore, these two obtained isostructural crystals exhibited similar blue light emission behaviors and solvation effects. [ABSTRACT FROM AUTHOR]

The preparation of a cocrystal is one of the effective strategies to tune the luminescence properties of organic crystals. In this work, four charge transfer cocrystals were constructed with isomeric substances of amino substituted dimethyl phthalates as the donors and 1,2,4,5-tetracyanobenzene as the acceptor. The emission range of the individual electron donors is from 400 nm to 505 nm, while all cocrystals have their emission redshift exceeding 100 nm. The tunable emission range of the charge transfer cocrystals is from 573 nm to 640 nm. All the obtained four cocrystals contain π–π stacking structures with the presence of π–π and C–H⋯π interactions. Fourier transform infrared spectroscopy and UV-vis spectroscopy demonstrated the presence of charge transfer interactions in the cocrystals. The tuning of the luminescence properties of the cocrystals was explained by the analysis of the crystal packing structure and the intermolecular interaction, and the distribution of frontier orbitals was obtained by DFT calculation. We believe our work is helpful to understand the relationship between the crystal structure and luminescence properties in the charge transfer cocrystals and provide guidance for the modulation of the luminescence properties. [ABSTRACT FROM AUTHOR]

Mechanically flexible crystals are generally obtained based on weak interactions in the aromatic systems. Here, we reported the remarkable 2D elastic bending behaviors in a nonaromatic organic molecular crystal. The strong hydrogen bonding interactions are also verified to play a crucial role in the reversible bending. [ABSTRACT FROM AUTHOR]

2,4-Dichlorophenoxyacetic acid (2,4-D) is a kind of plant growth regulator which exhibits hormesis effects at low dosages, while high dosages adversely affect the exposed organisms and act as herbicide. 2,4-D has low solubility, therefore, it is a good candidate for crystal engineering research to improve its solubility. This paper presents the preparation of five new multicomponent crystals of 2,4-D, including three salts with imidazole (IMZ), 2-aminopyridine (AAP), and 3-aminopyridine (BAP), and two cocrystals with isonicotinamide (ISO) and pyrazinamide (PYM) as coformers (CCFs). The five multicomponent crystals were first characterized by single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Molecular interactions, crystal packing, and structure similarity analyses performed using Hirshfeld surface and CrystalCMP confirmed the charge-assisted H-bonding sites and structural similarity among the solved crystal structures. The stability tests show that all five multi-component crystals exhibit excellent stability within 12 weeks under accelerated storage conditions (40 °C and 75% RH). Moreover, all the five multicomponent crystals of 2,4-D exhibit increased solubility, especially (2,4-D)+(IMZ)− that increased the solubility of the resulting salt by 70 times compared to the free acid 2,4-D. From the perspective of single-crystal structure and intermolecular interaction, the reasons for these changes in physical and chemical properties are further clarified. [ABSTRACT FROM AUTHOR]

Dapsone, a sulfonamide, is used to treat tuberculosis, leprosy, malaria, Kaposi's sarcoma, dermatoses and AIDS-related pneumonia. The purpose of this paper is to study the new solid forms of dapsone by using the crystal engineering method of cocrystallization. Based on the design concept of supramolecular synthons, the "–NH2⋯Npyridine" supramolecular synthon was used. 1-(4 pyridyl)piperazine (PYR) was selected as the co-former to prepare (1 : 1) and (2 : 1) DAP-PYR cocrystals, and the corresponding crystal structures were obtained by single crystal X-ray diffraction. The resulting cocrystals were fully characterized by a range of analytical techniques, including powder X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, etc. It was found that (1 : 1) and (2 : 1) DAP-PYR cocrystals formed mainly depending on the initial feed ratio of raw materials, which could be transformed into each other by adding quantitative DAP or PYR after mechanical grinding. Molecular interaction and structure analyses performed by Hirshfeld surface and 2D fingerprint plot analyses confirmed that the formation of the supramolecular synthon is the contribution of hydrogen bonding. Furthermore, the molecular electrostatic potential surface and intermolecular binding energy were calculated to visually identify the molecular hydrogen bonding sites, and it revealed that the strong hydrogen bonding interaction of "–NH2⋯Npyridine" promoted the formation of DAP-PYR cocrystals. [ABSTRACT FROM AUTHOR]

Calcium D -pantothenate, also known as VB5, is one of the most important feed additives. It typically assumes a needle-like morphology that easily agglomerates, resulting in poor flowability and low bulk density. Here, we develop a route to prepare calcium D -pantothenate in a block-like morphology with good flowability and high bulk density. Also, the solvent-mediated phase transformation of calcium D -pantothenate methanol solvate (D-PC·MeOH) into D -pantothenate tetramethanol monohydrate (D -PC·4MeOH·H2O) was investigated by in situ ATR-FTIR spectrometry and Raman spectrometry, and the data was subsequently correlated by the Johnson–Mehl–Avrami model. Results demonstrate that the rate-controlling step was the nucleation and growth of D-PC·4MeOH·H2O. Careful control over the thermal transformation process of D-PC·4MeOH·H2O enabled the formation of solvent-free calcium D -pantothenate in a block-like morphology. Molecular dynamics simulations enabled a deeper understanding of the effects of temperature on the phase transformation process. This work provides a framework to scale the production of calcium D -pantothenate to industrial levels. [ABSTRACT FROM AUTHOR]

In this study, curcumin 1,4-dioxane solvates (CUR–DIO) were obtained in two molecular ratios of 1 : 1.5 (CUR–DIO-1.5) and 1 : 1 (CUR–DIO-1) at different temperatures. In the two single crystal structures, the molecular conformation of curcumin is a planar structure and a curved structure, respectively. Moreover, the length of the hydrogen bond between the curcumin molecule and the 1,4-dioxane molecule indicates that with the increase in the system temperature, the difficulty of solvate formation increases, the solvent ratio decreases, and the inter-molecular hydrogen bond energy increases. In addition, with the increase in temperature, the crystal morphology changes from spherulites to rod-shaped crystals. The hollow spherulites of CUR–DIO-1 were obtained at 25 °C, and based on the ReactRaman data and microscope recording, a new formation mechanism of hollow spherulites was proposed. The formation mechanism and preparation method of organic small molecule hollow spherulites will play an important role in promoting the application of the hollow spherulite structures in the fields of drug loading, slow release and multifunctional drugs. [ABSTRACT FROM AUTHOR]

Boscalid, a commonly used fungicide, is mainly used for controlling gray mold, powdery mildew, and sclerotia. The aim of this study was to investigate the solid forms of boscalid systematically. The powder production of two anhydrous polymorphs (form I and form II) and monohydrate (H1) has been reported in the literature, while three novel solvates, i.e. S1 (1,4-dioxane solvate), S2 (N-methyl pyrrolidone solvate) and S3 (dimethyl sulfoxide solvate) have been obtained for the first time. The physicochemical properties of these six solid forms were fully characterized including power X-ray diffraction, scanning electron microscopy, Fourier transform-infrared spectroscopy, solid-state NMR, and thermal analysis. The crystal structures of all the six solid forms were determined from the single crystal data. The molecule conformations and packing arrangements in the crystal structures were analyzed and compared. Hirshfeld surface analysis was applied to reveal the intermolecular interactions. The packing coefficients of the crystal forms have been calculated to explain the formation of solvates. Finally, the desolvation process of solvates and the transformation relationship between different phases were explored. Meanwhile, the desolvation of solvate S2 leads to form II suitable for practical applications. [ABSTRACT FROM AUTHOR]

Levofloxacin is a fluoroquinolone and bears a broad-spectrum antibacterial effect. The polymorphism of levofloxacin was intensively studied, nevertheless, the landscape of polymorphs is not fully understood. Herein we reported for the first time the fully solved crystal structure of an anhydrous α form and three newly discovered solvates including n-propanol solvate, ethylene glycol solvate and acetic acid solvate. The successfully solved crystal structure of the anhydrous α form by single crystal X-ray diffraction was found to be in good agreement with the reported data by the SDPD (structure determination from powder X-ray diffraction data) method, but is significantly different from the one by the crystal structure prediction (CSP) approach. The comparison results suggest the wrong solved crystal structure of the α form using the CSP method. The newly reported n-propanol solvate, ethylene glycol solvate and acetic acid solvate of levofloxacin were fully characterized by powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and single crystal X-ray diffraction (except for the acetic acid solvate). It was found that the solvent molecules of the n-propanol solvate fill the channels and interact weakly with the active pharmaceutical ingredient (API) molecules, while they play crucial roles in the stability of the crystal structure. Further, the phase transformations among different solid-state crystal forms of levofloxacin were investigated in detail by variable-temperature powder X-ray diffraction. The results reveal that all of the newly discovered solvates can be directly dehydrated to an anhydrous γ form, which eventually converted into an anhydrous α form during subsequent heating. [ABSTRACT FROM AUTHOR]

The incorporation of drug–drug salts is known as an attractive strategy to not only improve physicochemical properties but also extend the field of combination drug delivery. Mefenamic acid (MFA) and tolfenamic acid (TFA) belong to effective but poorly soluble anti-inflammatory drugs used for treating both humans and animals. Piperazine (PPZ) has anthelmintic activities with a serious hygroscopic problem. To improve the physicochemical properties of such drugs and seek possible drug combinations, herein, four novel MFA\TFA–piperazine (PPZ) drug–drug salts with different stoichiometry (2 : 1 and 1 : 1) were designed and synthesized. As we expected, the experiments proved that their solubilities and dissolution properties were much better than that of MFA and TFA. Among them, the apparent solubility of the MFA–PPZ salt (1 : 1) improved about 130 times more than that of MFA in a mixture of water and ethanol. Meanwhile, these salts were non-hygroscopic based on dynamic vapor sorption analysis. Moreover, the obtained crystals were fully analyzed by single-crystal X-ray diffraction (SXRD), Hirshfeld surface analysis and a solvent mediated phase transformation study, which provided a better understanding of the crystal structure. The MFA–PPZ salt (2 : 1) and TFA–PPZ salt (2 : 1) possessed a similar crystal structure and their solubilities were also similar. In addition, the incorporation of PPZ in the crystal lattice destroyed the dimer form in the original MFA\TFA crystal and resulted in the formation of salts through a new ionic hydrogen bond. After contact with the solvents, PPZ was more likely to interact with the solvent molecules, which may have led to the acceleration of dissolution. [ABSTRACT FROM AUTHOR]

Four new solvent-free forms and five solvates of the widely-used herbicide nicosulfuron were found. The crystal structures of the reported form II and two new solvates (methanol and acetonitrile) were revealed for the first time. The results showed that nicosulfuron is conformationally flexible and that nine conformations are involved in these three solid forms, leading to different intermolecular interactions and packing patterns. The relationship between the polymorphs and molecular conformations was discussed through crystal structure analyses. In addition, comprehensive characterization of these forms was carried out to study the desolvation process and stability. The results showed that temperature-induced desolvation led to the appearance of new polymorphs, and that the moisture-dependent stability of nicosulfuron improved significantly compared to the marketed form Ia. [ABSTRACT FROM AUTHOR]

Full comparison of the experimentally determined crystal structure of the levofloxacin anhydrous α form from single-crystal X-ray diffraction with all the predicted structures from the CSP approach was supplemented. The previous conclusion in regard to the accuracy of predicted structures by crystal structure prediction (CSP) reported in our article (N. Wei, L. Jia, Z. Shang, J. Gong, S. Wu, J. Wang and W. Tang, CrystEngComm, 2019, 21, 6196–6207) was improved. The comparison results indeed demonstrated great similarities in the space group, unit cell parameters and even crystal packing of the predicted structures at rank 2 in the Z′ = 1 list to the experimental α form, despite the minor structural differences in the molecular conformation and packing arrangement. It was found that the levofloxacin molecules take a less stable conformer in energy rather than the stable conformer as previously expected. [ABSTRACT FROM AUTHOR]

Daidzein (DAID), known as a phytoestrogen, is an important bioactive flavonoid isolated from soybean and pueraria. However, its poor solubility and low dissolution rate limit its clinical application. With the aim of finding a form with fit-for-purpose physicochemical properties, a comprehensive solid-state screening experiment was performed. As a result, three polymorphs were discovered and the single crystal structure of stable form II was revealed for the first time. Form II was obtained in solvents with high β and π* values, while form III was produced under opposite conditions. To clarify this phenomenon, intermolecular interactions were investigated through single crystal structure analysis, solvent property analysis and computational methods. The results demonstrated that the compact arrangement of DAID and the solvents used played a critical role in solution crystallization. Moreover, the physicochemical properties of these three polymorphs were fully characterized, and the powder dissolution behavior was determined in pure water and pH 1.2 and pH 6.8 buffer solutions. The newly discovered form II exhibited better thermal stability, lower moisture sorption and faster dissolution rate compared with the other forms. [ABSTRACT FROM AUTHOR]

We report here a unique method for the preparation of aggregated crystals with well-defined shape and size using a solvent penetration-mediated phase transformation. An unusually fast phase transformation of sulfadiazine was observed. The aggregated sulfadiazine crystals are obtained through a water penetration mediated transformation of sulfadiazine N-methyl pyrrolidone solvate. The aggregated particles keep the same shape and size of the parent crystals. [ABSTRACT FROM AUTHOR]