Crystal Research and Technology最新文献

Cover image provided courtesy of Jianguang Zhou, Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, China.

Oiling-out is a common phenomenon in industrial crystallization processes that not only prolongs the total operating time but also leads to undesirable crystal morphology, making it challenging to control crystallization paths. This review provides a comprehensive overview of the oiling-out phenomenon in organic small molecule crystallization. First, the formation mechanisms of oiling-out are summarized from both thermodynamic and dynamic perspectives, providing the theoretical foundation for understanding the phenomenon. Then, the universal characterization methods for studying the oiling-out phenomenon of organic small molecules are introduced in detail, covering both offline and online analytical tools. Moreover, the regulation strategy for oiling-out, including solvents, impurities, seeding, temperature, and mixing methods are discussed. This paper also focuses on the application of oiling-out in co-assembly and crystal shape modulation. Finally, future opportunities and challenges are presented to address the current shortcomings and application bottlenecks in the study of organic small molecule oiling-out phenomena. This review aims to provide valuable insights and guidance for researchers working on the crystallization of organic small molecules, particularly in the pharmaceutical industry, to better understand, control, and utilize the oiling-out phenomenon.

Recent observations of crystallization by thermal chemical vapor deposition systems indicate that the classical mechanism of nucleation and growth is followed. Information on aragonite nanocrystal growth and formation on substrate have been lacking due to the lack of reports on diffusional growth that can observe calcium carbonate nucleation processes in thin film formation. This report is important due to the additive-free method able to grow stable single-phase nanocrystals without the presence of other phases, amorphous or impurities. This work demonstrates homogeneous nucleation occurred in gas phase reaction in a constant flow of carbon dioxide gas (100 sccm) with optimally 0.5 M calcium chloride precursor in atmospheric pressure at 400 °C resulting in a calculated crystallite size of 27.8 nm. X-ray diffraction and energy dispersive spectrometer confirm the presence of calcium carbonate nanocrystal, whereas its structural changes are observed by its micrograph from field emission scanning electron microscope. The aim is to convey its importance in gaining control of aragonite nanocrystal morphology and structural properties, and thus generate nanocrystals with controlled phase. This work may contribute to development of more sensitive and crucial applications of calcium carbonate nanocrystal thin film such as in biosensors and biomedical.

Hydroxychloroquine sulfate is a common drug for the treatment of rheumatoid arthritis. However, the disadvantage of this drug is that it needs to be taken continuously for 3–6 months to be effective and compliance of patients is poor. In this work, four new salt forms of hydroxychloroquine are successfully prepared whose crystal structures and properties are confirmed by a series of solid-state characterization methods, including infrared spectroscopy, single crystal X-ray diffraction, powder X-ray diffraction, thermal analysis, and dynamic vapor sorption analysis. The hygroscopicity, stability, equilibrium solubility, and intrinsic dissolution rate of the four new salts are also tested. The moisture absorption, solubility, and intrinsic dissolution rate of newly prepared salts are significantly reduced, and the dissolution rates of 1-hydroxy-2-naphthoate and 1,5-naphthalenedisulfonate salts are only 1/158 and 1/335 of that of the therapeutically used sulfates, respectively. It is expected that they are potentially useful to be developed into a sustained-release formulation, which can greatly improve the dosing compliance for rheumatoid arthritis treatment.

Herein stacked layers of iron selenide (FeSe₂) thin films are deposited by the physical evaporation technique and thermally annealed. An in situ monitoring of the crystallinity during the annealing process has shown that the crystallinity is reached at 100 °C. The crystallinity of the films that preferred the orthorhombic phase is enhanced with increasing annealing temperature. Evidences about the improved crystallinity are presented by the increased crystallite and grain sizes, decreased microstrain values, decreased stacking faults, and decreased defect densities with increasing annealing temperature. Optical investigations have shown impressive effect of the annealing process on the optical reflectance, optical contrast, and light absorbability. Namely, respective improvement percentages exceeding 170%, 64%, and 140% is achieved near E≈2 eV for samples annealed at 200 °C for 20 min. Both direct and indirect optical transitions are dominant in the film. In addition the annealing increased the dielectric constant in the spectral range of 1.17–4.20 eV. Maximum dielectric enhancement by 214% is reached near ≈2.10 eV. Moreover, the annealing process increases the optical conductivity and drift mobility of the FeSe₂ films. The improvement in the crystallinity that resulted in enhanced optical properties makes the thermally annealed FeSe₂ films promising for optoelectronic technology applications.

Aspirin, a commonly used pharmaceutical therapeutic pharmacological substance, exhibits cross-nucleation (intergrowth or overgrowth) of stable polymorphic Form-I over the preferably required metastable polymorphic Form-II, which creates a bottleneck issue in the solution crystallization of aspirin in most organic solvents and their mixtures. Controlling the overgrowth phenomenon is a key factor for designing the pharmaceutical drug material aspirin with desired properties. Hence, our present work chose a novel template-assisted swift cooling crystallization with selected templates like copper-wire and nylon 6/6 polymer, and also N-N-Dimethylformamide (DMF) as a solvent. The pure solution in the absence and the presence of a nylon 6/6 template in all the experimental supersaturation ranges achieves only thermodynamically stable polymorphic Form-I of aspirin with slightly different morphologies. Contrarily, the presence of a copper-wire template induces both stable and metastable polymorphs of aspirin depending on the level of supersaturation in the mother solution. The effect of templates on the nucleation kinetics of aspirin polymorphs is estimated using classical nucleation theory, and the determined values exactly match with experimental results. The polymorphic nature of the grown crystals is ascertained by powder X-ray diffraction (PXRD), single crystal X-ray diffraction (SCXRD), and differential scanning calorimetry (DSC) analyses.

A recent interest attaches to the derivatives of the (2-benzylsulfinyl)benzoic acid as inhibitors of human carbonic anhydrases (hCAs), an action that can be applied in innovative therapies. A set of crystal structures of six sulfides and six enantiopure sulfoxides related to this scaffold, taken from the literature, or derived from the work on the asymmetric synthesis of sulfinyl compounds, is investigated. The lattice energies of these structures are estimated by means of the Crystal Explorer 21 program. The weak interactions building up the crystal structures are identified, and their contributions are analyzed in comparison with the calculated lattice energies. The most stable conformations in the solid phase are identified. It is worth observing that the sulfides of the scaffold under investigation behave almost in the same manner; on the other hand, the presence of the sulfinyl group of the sulfoxides adds complexity, that shall be taken into account in future docking calculations of these molecules with the hCAs enzymes.

A new polymorph of maltol, a food and intermediate pharmaceutical material, is discovered through solution crystallization process using a mixed solvent of water and ethanol with l-menthol as an additive. It belongs to monoclinic crystal system with lattice parameters: a = 7.136(8) Å, b = 24.23(3) Å, c = 7.020(8) Å, and β = 106.22(3)°, volume =  1165 (2) Å³ and the refinement factor is R = 6.64%. With single crystal X-ray diffraction (SCXRD) data as input, the intermolecular interactions between the new polymorph of maltol is investigated through Hirshfeld surface analysis, the higher percentage of overall interaction between the polymorph (H…H) interaction, and the (O…H) interaction contributes more to the generation of new polymorph. The 2D finger print plot depicts the interactions are mainly due to the hydrogen bonds.

This study investigates the crystallization of acetaminophen (ACET) in ultrapure water and a 10 wt.% aqueous polyacrylic acid (PAA) solution using non-photochemical laser-induced nucleation (NPLIN) for the first time. Using a 532 nm nanosecond laser, two distinct crystal morphologies—rhombic and tetragonal plate-like—are formed in both solvents after adding impurities. Notably, the PAA solution showed a reduced number of crystals and slower growth rates compared to ultrapure water, suggesting that the acidic polymer modulates crystal growth. Interestingly, crystals are not induced by the laser without impurities. However, impurities like copper phthalocyanine (CuPc) or boron carbide (CB₄) enabled successful NPLIN, with CB₄ showing higher nucleation efficiency than CuPc. The study also explores how laser power affects nucleation probability and identifies potential laser energy thresholds. Experimental data on ACET crystal sizes over time are fitted to derived equations, which accurately represented trends and predicted results. The nanoparticle heating mechanism and the role of acidic polymers in affecting nucleation probability and growth rate are discussed, along with potential mechanisms for changes in crystal morphology.