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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]

The newly discovered growth self-inhibition phenomenon of tautomeric crystals is now generalized to the demostrope (form B) of irbesartan that displays intra-annular tautomerism in neutral aqueous solutions. The dynamic intra-annular tautomer inter-conversion on the surface is the key factor. Our findings provide implications for producing and engineering tautomeric materials. [ABSTRACT FROM AUTHOR]

Crystallization is an important unit operation in industry, and proteins are widely studied owing to their biological activity and multiple functions. Protein crystals can not only facilitate the elucidation of protein structural information but also have important prospects in biopharmaceuticals. However, owing to their high molecular weight and complex structure, most proteins are difficult to crystallize or the crystallization processes are difficult to control effectively. This paper aims to provide an overview of recent reinforcement techniques for protein crystallization. Several important additive applications and principles in protein crystallization are comprehensively reviewed, including ionic liquids (ILs), deep eutectic solvents (DESs), and molecularly imprinted polymers (MIPs). The mechanism of external fields, including magnetic, electric, ultrasonic, shear, and light fields, enhancing protein crystallization are described and summarized. Finally, the challenges and future research prospects of protein crystallization are proposed. This work is expected to guide the rational design of the protein crystallization process. [ABSTRACT FROM AUTHOR]

We explore the polymorphism of a weakly polar molecule, dibenzoylmethane, in which the intramolecular hydrogen-bonded enol "chelated" form is favoured. A simple geometric method on the basis of interatomic distance to visualize and count favourable connections between non-hydrogen atoms was constructed to judge the strength of intermolecular interactions in polymorphs of this kind of weakly polar molecule. The number of total favourable connections mirrored with resonance-assisted hydrogen bonds (RAHB) and aromatic interactions in DBM polymorphs increases from forms I to III, in agreement with the order of their equivalent interaction energies, proving that it is feasible for this geometric approach to be used in this weakly polar system. [ABSTRACT FROM AUTHOR]

Porous hollow spherical particles benefit from special structural features and fascinating physicochemical properties resulting in widespread application. Particularly in pharmaceutical engineering, they have significant advantages for direct compression and drug combination. However, their large-scale application is severely hindered by the limitations of traditional production methods in terms of the use of complex equipment, high energy consumption and high organic solvent usage. In this work, we have developed an oiling-out directional agglomeration method to produce porous hollow indomethacin spherical particles by a simple heating–quenching–drying operation without the use of organic solvents and templating agents. Compared to commercial flake crystals, the indomethacin spherical products have higher average tensile strength (471% increase) and higher plastic deformability, i.e. better tabletability and compressibility. More importantly, nifedipine is successfully loaded into porous hollow indomethacin spherical particles based on molecular polarity differences. The composite particles with a core–shell structure exhibit excellent powder properties, tableting and anti-degradation performance, while also achieving sequential release of drugs. This contribution provides the basis for the development of drug formulation strategies and the design of functional crystalline materials. [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]

The pathological mineralization of calcium oxalate monohydrate (COM) crystals in vivo inevitably brings renal injury wherein natural macromolecules play an indispensable role in regulating the process. However, the role of macromolecules in crystal growth is more complicated and less well understood. In this study, we innovatively propose two proteins extracted from earthworms, lumbrokinase (LRK) and earthworm protein (EP), as potent modifiers of calcium oxalate (CaOx) crystals. Our research shows that LRK and EP inhibit COM formation and initiate the calcium oxalate dihydrate (COD) phase, which is more easily excreted out of the body. Through a series of combined macroscopic and microscopic experimental techniques, we reveal the site-specific adsorption of inhibitors on the COM (121¯) and (021) surface, resulting in a reduction in the aspect ratio. In situ atomic force microscopy (AFM) measurements show that LRK and EP specifically inhibit the advancement of COM surface steps through more than one inhibition mode. In general, the discovery of natural macromolecules from earthworms as potent inhibitors of COM crystal formation provides some insights into the appropriate formulation of inhibitors, which could prevent the formation of undesired stones in the kidney. Our findings shed light on nature's remarkable mineralization capabilities and outline fabrication strategies for advanced materials. [ABSTRACT FROM AUTHOR]

The current oiling-out spherical agglomeration technology overcomes the shortcomings of biohazardous solvents and complex equipment of the traditional spherical granulation technologies in the pharmaceutical industry. However, it is difficult for high melting point drugs to oil-out in water, so this novel green technology is only applicable to low melting point drugs, which severely limits its application. This work developed a two-step oiling-out (TSOO) mechanism suitable for high melting point drugs thereby increasing the number of potentially applicable substances for this technology by about 150%. In the TSOO mechanism, the high melting point drug first undergoes co-oiling-out with a specific oiling-out mate in an aqueous solution (first step), followed by the removal of the oiling-out mate forming single-oiling-out droplets of the high melting point drug (second step), which eventually forms spherical particles of the high melting point drugs. Process analytical technology tools including IR spectroscopy, FBRM and PVM were applied to monitor the preparation process in real time, which verified the TSOO mechanism experimentally. Based on the proposed mechanism, spherical particles of 13 drugs (melting point range is 385.15–526.15 K) with good powder properties, high yield and adjustable particle size distribution were successfully prepared in water at a low temperature. This demonstrates that the TSOO mechanism allows more drugs to be spherically granulated in a green way. Furthermore, the molecular simulation-based design strategy of TSOO spherical agglomeration significantly saves the time required and reduces the use of chemicals for the TSOO mechanism promotion. [ABSTRACT FROM AUTHOR]

The multiphase cobalt–iron spinel was firstly synthesized via a facile cold plasma method and applied as a bifunctional electrocatalyst for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Compared with the single-phase obtained by the traditional calcination method, the CoFe2O4 and Co3O4 phase were obtained by the plasma method. The multivalence states of cobalt and iron facilitated electron transport in electrochemical reactions. The plasma sample had a small particle size (5 nm) due to the low operation temperature. Notably, electron impact produced more oxygen vacancies and a larger surface area on CoxFeyO4, which increased the active sites and electronic conductivity. Electrochemical investigations indicated that the multiphase spinel obtained with a quasi-four-electron transfer process showed an onset potential of 0.76 V versus the RHE for the oxygen reduction reaction. In the oxygen evolution reaction, the potential of current density at 10 mA cm−2 was 1.53 V versus RHE. As for the overall electrocatalytic activity, the multiphase spinel had a ΔE (the difference between E10(OER) and E1/2(ORR)) of 0.89 V, exhibiting greater bifunctional activity than the other prepared catalysts. [ABSTRACT FROM AUTHOR]

Uric acid (UA) is the end product of purine metabolism and is widely found in nature. Excess uric acid will result in the deposition of pathological uric acid crystals in the kidney. However, few studies have focused on the effects of components in the human body on the crystallization of uric acid. Herein, we found multiple effects of alkali metals (Na+, K+) on uric acid dihydrate (UAD) crystal growth, which is one of the main components of urinary stones. Optical microscopy (OM) and scanning electron microscopy (SEM) were employed to detect the crystal morphology, and long rod-like crystals and hierarchical crystals were found in the presence of Na+ and K+, respectively. Powder X-ray diffraction (PXRD) and micro-Raman spectroscopy verified that the crystal structure remained unchanged in the presence of ions. In addition, single-crystal growth experiments revealed that Na+ inhibited growth along [010] and [100], and K+ promoted growth along [100] but suppressed growth along [010]. The step growth of the UAD crystal was measured by atomic force microscopy (AFM), which indicated the inhibition of crystal growth by Na+ due to kink blocking, yet the promotion of crystal growth by K+ resulted from rough growth. Our studies showed that ions in the human body not only can maintain electrolyte balance but also can affect the crystallization of pathological crystals, which provides a suggestion for a rational diet for patients with hyperuricemia and urinary stones. [ABSTRACT FROM AUTHOR]

Antisolvent crystallization is a significant unit operation in the pharmaceutical industry, especially in drug crystal property optimization. This paper firstly highlights the applications of antisolvent crystallization in crystal engineering. Antisolvent crystallization can effectively control the product properties, such as polymorphism, morphology, and particle size optimization, to improve drug therapeutic effect. This paper also includes the process intensification pathways of antisolvent crystallization in the pharmaceutical field. Process parameter optimization and device and structure modification are considered as feasible approaches. Then, coupled techniques with antisolvent crystallization, including ultrasound and membrane intensification, are also summarized. Finally, the models and applications of continuous antisolvent crystallization are introduced to better design and optimize the processes. Also, critical concerns and opportunities for further research and perspectives are discussed. [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]

In order to improve the aqueous solubility of clotrimazole (CLT), an effective antifungal agent, its new multicomponent crystals were developed according to crystal engineering. To efficiently synthesize the multicomponent solids, a protocol which combined a virtual cocrystal screening tool based on the conductor-like screening model for realistic solvents (COSMO-RS) and the experimental liquid-assisted grinding (LAG) method was applied. As a result, fourteen multicomponent crystals were obtained from 21 potential coformers, including 5 previously reported ones. Nine novel multicomponent crystals were identified and characterized by single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and Fourier-transform infrared spectroscopy. Intermolecular interactions were elucidated by Hirshfeld surface analysis, and the origin of the cocrystals/salts was explained using molecular electrostatic potential surfaces. Finally, powder dissolution experiments were carried out. Compared with CLT, some multicomponent crystals showed an improvement in solubility (3.13–1.53 times) and dissolution rate. [ABSTRACT FROM AUTHOR]

A jumping crystal of the channel-type hydrate of spironolactone–saccharin cocrystals was presented as the first example of a crystal that jumps without changes in both the lattice constant and the molecular conformation, emphasizing the general applicability of our newly proposed design concept that introduces an easy-to-escape component, the jumping-mate, to generate crystal motions. [ABSTRACT FROM AUTHOR]

Despite the toxicity of cadmium, CdS has been used as an electron transport layer (ETL) in highly efficient Sb2(S,Se)3 solar cells for a long time. In this work, a bilayer structure ETL, denoted as Zn(O,S)/CdS, has been prepared as a substitute for pure CdS in S-rich Sb2(S,Se)3 solar cells. This achieves two important goals related to the current use of CdS-based Sb2(S,Se)3 photovoltaics, namely, due to high transmittance and a significant reduction of CdS usage, an increase of the short circuit current density in the short-wavelength range (by about 1.5 mA cm−2) and a decrease of the usage of CdS (by about 75%). Interestingly, the fabricated FTO/Zn(O,S)/CdS/Sb2(S,Se)3/Spiro/Au device achieved an impressive power conversion efficiency of 9.62% and shows high stability without the light-soaking (LS) effect and hysteresis. To date, this conversion efficiency value represents the highest efficiency of all Sb-based solar cells with Cd-free or reduced-Cd ETLs based on either substrate or superstrate device configurations. [ABSTRACT FROM AUTHOR]

This work aims at developing a green and highly-efficient technique, which enables co-crystallization and co-agglomeration of drugs, or the crystallization of one drug and simultaneous agglomeration with another drug, in pure water taking advantage of oiling-out. By establishing the phase diagram and making use of the oil droplets formed in an oiling-out system, spherical co-agglomerates containing desired ratios of drugs, ibuprofen (IBU) with a second active pharmaceutical ingredient (API), including L -menthol (MT), praziquantel (PZQ), rivaroxaban (RXB) and lenalidomide (LDM), were successfully prepared, simply relying on a heating–quenching operation. Forming processes of the spherical co-agglomerates involved two kinds of mechanisms: co-oiling-out and single-oiling-out mechanisms, making the oiling-out co-agglomeration (OOCA) technique suitable for a wide range of applications in pharmaceuticals. Particularly, the co-oiling-out mechanism, which was proposed and designed, for the first time in this work based on ternary phase diagrams of (API1–API2–water), uniform oil droplets of two APIs were generated, guaranteeing a high degree of content uniformity in the co-agglomerate products. The OOCA technique developed in this work can not only incorporate crystallization and granulation into one unit operation, but also help in achieving drug combination (polypills). An effective screening strategy for drugs applicable to the OOCA technique was established by simulation and computation, greatly reducing the utilization of chemical substances and helping save time in the promotion process of OOCA. [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]

Ostwald's rule of stages is one of the most important empirical rules to understand the crystallization behavior of crystalline materials, however, it may not be always satisfied. Herein, we demonstrate that crystallization outcomes of citric acid (CA) in aqueous solutions violate this rule. The anhydrous phase was found to nucleate at the whole temperature range (below or above the transition point of the system), whereas, the monohydrate form only nucleated at high supersaturation below the transition point. The unexpected appearance of the anhydrous phase is shown to have been influenced by solution ionization and its crystallization kinetic advantage over the monohydrate form. [ABSTRACT FROM AUTHOR]

Crystal purity is of primary importance for pharmaceutical crystallization, and the inclusion of mother liquids inside the crystals poses a great challenge and threat to the product quality and purification efficiency. It is well recognized in industry that mother liquids can be included inside the crystals; however, the underlying formation mechanism remains poorly understood. Herein, we investigated the formation of liquid inclusions during crystallization of a model compound tetramethylpyrazine (TMP), which is a bioactive alkaloid drug, with an aim to better understand and hence control the liquid inclusions formed inside the crystals. The formation of mother liquid inclusions inside TMP crystals was fully characterized by optical polarizing microscopy, micro-Raman spectroscopy, and powder X-ray diffraction. Three types of fluid inclusions were observed in TMP crystals, and the single-phase liquid inclusions dominate. The effects of initial supersaturation and temperature on the formation of liquid inclusions were studied both qualitatively and quantitatively by optical microscopy and gas chromatography. It was found that high supersaturation and high temperature were favorable to the mother liquid inclusions in the resultant crystals. Moreover, the amounts of liquid inclusions inside the crystals are positively correlated with the growth rate of the TMP crystals. Solvent effects on the formation of liquid inclusions were also studied by choosing four types of solvents of distinct polarity. The results showed the solvent dependence of the formation of liquid inclusions, and the TMP crystals harvested from ethyl acetate displayed the most remarkable inclusions of mother liquids while the fewest liquid inclusions were found in isopropanol. Furthermore, the inclusion amounts of mother liquids can be correlated with the growth rates in different solvents but could not simply be correlated with only one type of property of the four solvents such as polarity, viscosity, dielectric constant, or surface tension. Finally, the inclusion of mother liquids inside TMP crystals was suggested to be effectively suppressed by crystallization at lower temperature and supersaturation, as well as in solvents with greater polarity and viscosity. [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]

In template-directed crystallization, especially from solution, two pathways—homogenous nucleation and heterogeneous nucleation—often compete with each other, and the resultant pathway is strongly dependent upon crystallization conditions and template properties. Apart from the effects of molecular and stereochemical structures, the functional group ordering, the amount of template, and the applied solvents also play key roles in the resultant crystallization outcomes, but these are often overlooked. Herein, we systematically investigated these effects, in particular the functional group ordering of template hydrochlorothiazide and sulfathiazole, on the template-directed crystallization of pyrazinamide. It was found that the effectiveness of template regulation on the selective nucleation of γ form pyrazinamide is significantly affected by the amount of template and the solvent systems, where weak solute–solvent interactions facilitate template regulation. Surprisingly, the nucleation of γ form pyrazinamide can be directed by the ordering and specific orientation of the template functional groups hydrochlorothiazide or sulfathiazole. Functional group ordering is further proven to help the alignment of solute molecules and induce the nucleation of γ form. This work highlights the critical roles of functional group ordering and specific orientation on template-directed pharmaceutical crystallization. [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]

Crystal engineering is aimed at controlling the crystal forms and desired properties from the view of molecular engineering, which is important for the production of high-value-added products. dl-Methionine (dl-met) usually crystallizes in a concomitant mixture with the known metastable α-form and stable β-form from a pure aqueous solution. In this contribution, we first applied molecular dynamics (MD) simulations to study the effects of the tailor-made additive and found that dl-leucine (dl-leu) might enable us to stabilize the metastable form. To validate our idea, we performed experiments including cooling crystallization with isothermal and non-isothermal methods, nucleation induction time measurements, solvent-mediated phase transformation and crystal growth rate measurements. It was found that on increasing the concentration of dl-leu, the nucleation of the β-form and the transformation of the α-form were hindered. When the concentration of dl-leu reached above 0.02 mol L−1, hexagonal crystals other than foliaceous crystals could be obtained. Hence, the metastable α-form of dl-met with fine crystal habits and high temporal stability was prepared. [ABSTRACT FROM AUTHOR]

In this work, the influence of sodium dodecyl benzene sulfonate (SDBS) on the primary nucleation and growth of thiamine nitrate (VB1) has been investigated. At a given supersaturation, SDBS significantly impedes the nucleation rate of VB1. The results were analyzed through the probability distribution function of the induction time. Furthermore, the growth rate of VB1 in pure water and in the presence of SDBS was determined by single seed crystal growth experiments. It was found that the retardation by SDBS of the axial direction growth of VB1 crystals is much stronger than that of the radial direction growth. Molecular dynamics simulations (MD) were employed to delineate the effects of SDBS on the nucleation and growth of VB1. The MD simulation results manifested that the strong steric hindrance of SDBS molecules, the hydrogen-bonding and electrostatic interactions between SDBS molecules and VB1 molecules hinder the nucleation rate of VB1. Moreover, the results revealed the highest bonding energy between SDBS and the (1 0 0) surface, and the bonding energies between SDBS and all corresponding surfaces obey the following trend: (1 0 0) ＞ (1 1 0) ＞ (1 1 1) ＞ (1 0 2) ＞ (1 0 −2) ＞ (0 1 1) ＞ (0 0 2), which can provide a reasonable explanation for the experimental results. [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]

In this research, the crystal structure of antidiabetic drug gliquidone (GQD) is analysed and multicomponent crystals such as piperazine (PPZ) salt and eutectics are designed and synthesized based on its structural features. Three polymorphs of the salt are obtained together with five solvates. Fortunately, four single crystals of the salts are determined for the first time. The results reveal that the high hydrogen bond-forming ability of PPZ plays a vital role in breaking the original packing of GQD and resulting in salts instead of eutectics. Finally, comprehensive characterization of the salt polymorphs is performed and the result shows that the powder properties and powder dissolution are enhanced by the salt formation compared with the parent form. [ABSTRACT FROM AUTHOR]

In this work, we studied the effect of piperazine, a major by-product, acting as an additive, on the thermodynamics and nucleation kinetics of the triethylenediamine (TEDA)–methyl tertiary butyl ether (MTBE) crystallization process. It was found that the solubility of TEDA in MTBE increased with increasing amount of piperazine. The interactions of piperazine, TEDA and MTBE were investigated by using molecular dynamics simulation based on Materials Studio. The experimental data of maximum supercooling ΔTmax, a measurement of the metastable zone width (MSZW), were analyzed to describe the role of piperazine in the nucleation kinetics of the TEDA–MTBE system. Modified Sangwal's theory was also employed to understand the nucleation behavior in both pure and impure systems. Improved solubility and narrower MSZWs can be achieved by controlling the amount of piperazine in the TEDA–MTBE system. Based on the thermodynamics and nucleation results, a TEDA product with a large particle size can be obtained by adjusting the supersaturation in a one-step purification process, eliminating the conventional recrystallization step. [ABSTRACT FROM AUTHOR]

There has been much interest in the role of solution chemistry in determining the polymorphic formation of organic crystals. For convenience, the predominantly investigated systems are those that contain distinct building blocks among the polymorphs; in this work, an important drug excipient, D-mannitol (D-man), was selected as a case study, which represents a polymorphic system that only has the same building blocks. By employing the Hirshfeld surface analysis and molecular dynamics (MD) simulations, D-man's crystal packing and the solvation nature in different solvents were studied on the molecular level. The results suggest that there is a direct link between the solution speciation and crystal structure, and two distinct solvation modes were identified along with their impacts on nucleation. This study indicates the significant role of solvation in determining D-man's nucleation and offers new insights into the research on systems that do not have distinct building blocks among the polymorphs. [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]

The transport and magnetic properties of LaAlO 3 /SrTiO 3 (LAO/STO) heterostructure have been studied during cooling and warming. The strain gradient perpendicular to the surface of the heterostructure increases with the thickness of LAO film. The conductivity accelerated recoveries (CAR) are found at 80 K and 176 K in the interface of LAO/STO sample with millimeter scale, and are more obvious for thicker LAO layers during warming. These two recovering temperatures correspond to the migrating energies of oxygen single vacancy and divacancy trapped by polarized domain walls, separately. This indicated that domain walls diffuse along the longitudinal direction and expand to larger area due the strain gradient perpendicular to the interface. The stable and precise accelerating recovering temperatures make the sample at a larger scale a potential widely applied temperature standard reference. The magnetization measurements reveal the coexistence of paramagnetic and diamagnetic in the LAO/STO samples at whole temperature from 2 K to 300 K. The abnormal electric resistance rise is observed with the decreasing temperature below 25 K for the samples of 7 and 15 LAO layers. This anomaly is attributed to the Kondo effect below 25 K and weak anti-localization below 5 K due to the weightier paramagnetic content. The larger diamagnetic content suppresses these contributions in 25 LAO layers sample. This work provided an insightful view that the strain modified structure domain leads to the enhancement of CAR effect, which helps to achieve a better understanding of domain related physics in the LAO/STO system., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)