Crystal Growth & Design最新文献

Design and synthesis of multinary metal–organic frameworks (MOFs) are of paramount importance but challenging. Nevertheless, pore space partitioning has provided a valuable avenue to isolate ternary MOFs bearing advanced gas storage and separation properties. Herein, a rare (3,3,8)-c Fe-BQDC-BTC-TPBTC MOF was constructed by means of solvothermal reaction between iron ions, a zigzag dicarboxylate H₂BQDC ligand and another two C₃-symmetry TPBTC and H₃BTC linkers. In contrast to the frequently observed single hexagonal channel type, the acs net within Fe-BQDC-BTC-TPBTC possesses two types of hexagonal channels. One of them is capable of fitting two differently sized C₃-symmetry ligands, engendering an unusual quaternary MOF with a new partially partitioned acs 2/3-plus net eventually. Fe-BQDC-BTC-TPBTC demonstrates a complex bimodal porous system concomitant with a potential separation property toward the MTO product of ethylene and propene mixtures as verified by single gas adsorption and transient column breakthrough experiments, respectively.

This study applies an innovative two-stage continuous manufacturing process for atorvastatin calcium (ASC), focusing on the integration of process intensification through spherical agglomeration. The integrated continuous crystallization–spherical agglomeration (CCSA) process significantly improves the crystallization of active pharmaceutical ingredients (APIs), traditionally focused on downstream processing efficiency. The method integrates continuous crystallization with spherical agglomeration in a two-stage continuous mixed suspension mixed product removal (MSMPR) system. This integration enables the decoupling of nucleation and growth mechanisms from agglomeration, facilitating the continuous production of ASC with optimized physical and processing properties. The intensified system not only enhances particle size and morphology but also significantly improves the downstream processing efficiency, such as filtration, drying, and tableting, while maintaining or enhancing the drug molecule’s efficacy. It also allows for bypassing certain downstream unit operations, such as granulation, that are generally bottleneck processes in ASC manufacturing. The versatility of this approach is evident in its ability to tailor the properties of ASC for maximum bioavailability and processing efficiency, marking a significant advancement in the implementation of process intensification in ASC manufacturing via a novel spherical agglomeration route combined with continuous manufacturing.

Olaparib (OLA) is an insoluble targeting antitumor drug for the treatment of ovarian cancer. Herein, polyamorphism of OLA was systematically studied aiming to improve its solubility and dissolution properties. Three amorphous forms of OLA were prepared by ball milling (form I), rotary evaporation (form II), and melting (form III) methods, and the effects of polyamorphism on the morphology, thermodynamic properties, dissolution and gelation phenomenon, and the stability of OLA were studied for the first time. The results indicate that morphology has an impact on the gelation process of amorphous forms and thereby affects the dissolution of the drug. Among them, form II shows the best solubility and dissolution rate due to its slightest gelation, as well as relatively good stability and tabletability, which exhibits good application prospects in the amorphous solid formulation development of OLA.

This study aims to prepare a stable crystal-co-agglomeration (CCA) process for combining the antibiotics trimethoprim (TMP) and the anti-inflammatory niflumic acid (NFA) as well as the enhancement of powder properties. A novel TMP–NFA salt monohydrate was synthesized and characterized through multitechniques for the first time. Subsequently, the antibacterial effectiveness of TMP–NFA salt monohydrate against Staphylococcus aureus and Shigella flexneri was found to be improved (P < 0.05) compared with that of TMP at certain concentrations, achieving a synergistic effect of TMP and NFA. Based on these findings, spherical agglomerates of TMP–NFA salt monohydrate with superior powder properties including improved flowability (Carr’s index decreased by 37.5% and Hausner’s ratio decreased by 16.3%) and tabletability were produced using an efficient CCA process. Hence, the optimized spherical agglomerates of the drug–drug salt technique provide a promising approach to simultaneously enhance the powder properties and synergistic effect of active pharmaceutical ingredients. The development of such drug–drug salts holds great potential for advancing pharmaceutical formulations and therapeutic outcomes.

A desirable MOF-on-MOF-based ratiometric fluorescent probe (denoted as HPU-26@ZIF-8@Cit@Eu) was designed through the seed-mediated method for classifying phenylglyoxylic acid (PGA, a real internal exposure level of styrene) and 2,6-dipicolinic acid (DPA, a unique bacterial endospore biomarker) with high selectivity and sensitivity. Characterization techniques were carried out with the PXRD pattern, XPS spectra, UV–vis absorption spectra, and DFT-calculated HOMO and LUMO energies for proven mechanisms. The results indicated that PGA could affect the LMCT-ET process in HPU-26 and be binded to Eu³⁺ in ZIF-8, thus resulting in a significant increase both in the blue fluorescence emission peak at 476 nm and the red fluorescence emission peak at 620 nm. According to the fluorescence intensity ratio (I₆₂₀/I₄₇₆), the limit of detection (LOD) reached as low as 0.63 μM within a wide concentration range from 0 to 100 μM, and a noticeable color change from blue to red could be observed. However, upon exposure to DPA, the energy transfer between Zn²⁺ and the ligand was influenced sharply, without prejudice to the fluorescent intensity of Eu³⁺ in ZIF-8. These phenomena made this probe with a stable reference signal have an ultralow LOD of 0.26 μM for DPA in the range of 0–175 μM, converting the fluorescence color from dark blue to bright blue. Meanwhile, the developed probe was applied to the construction of logic gates and hydrogel-based film for the determination of PGA and DPA in real samples with the help of a smartphone.

Pharmaceutical cocrystals are of interest to the pharmaceutical industry due to their novel potential for improving the physicochemical characteristics of old APIs. However, cocrystal screening and following synthetic optimization consume time and effort. A two-component crystalline phase of (S)-ibuprofen and l-phenylalanine with 2:3 stoichiometry (Ibu-Phe) is reported. High-quality Ibu-Phe cocrystal was synthesized easily by the liquid-assisted grinding (LAG) method, but some impurities remained. The crystal structure of Ibu-Phe can be solved ab initio from 3D ED/MicroED. Furthermore, a nearly pure Ibu-Phe cocrystal sample can be obtained under the guidance of stoichiometry from 3D ED/MicroED following synthesis optimization in a few attempts.

Robust and reliable synthons can facilitate the synthesis of predictable and complex supramolecular assemblies. In this study, we employ triply activated halogen-bond donors as a driver for cocrystal formation and examine the influence of the sigma-hole potential for controlling the stoichiometry of binary cocrystals of phenazine. Six new crystal structures are presented for ketone:phenazine binary cocrystals as well as six crystal structures for ester:phenazine cocrystals. The combination of structural chemistry and theory provides an increased understanding of how controlled variation of the molecular electrostatic potential on the halogen-bond atom can control the stoichiometry in the resulting binary cocrystals.

Development and production of novel high-performing nitrogen-rich energetic compounds with a safe and environmentally friendly nature are significant in the pursuit of new-generation green energetic materials. Despite the growing interest in energetic cations in recent years, fused heterocyclic energetic cations have rarely been reported. In the following study, a series of energetic materials comprising purine compounds and oxidants were prepared using a significant noncovalent self-assembly method. Elemental analysis, mass spectrometry (MS), IR spectroscopy, and differential scanning calorimetry (DSC) were used to characterize these synthesized compounds thoroughly. The structures of supramolecules (1–4) were further verified by employing the single-crystal X-ray diffraction technique, and standard BAM methods were used to determine the sensitivities. Furthermore, theoretical calculations and experimental data were used to elucidate the relationship between the structure and properties. Comprising several benefits such as simple and facile preparation, high yield, high density, superior thermostability, insensitive nature, and good detonation properties, the synthesized compounds are regarded as competitive green energetic materials.

A methodology for the prediction of face-specific relative dissolution rates for single-faceted crystals accounting for inequivalent wetting by the solvent is presented. This method is an extended form of a recent binding energy model developed by the authors (Najib et al., Cryst. Growth & Des. 2021, 21(3), 1482–1495) for predicting the face-specific dissolution rates for single-faceted crystals from the solid-state intermolecular binding energies in a vacuum. The principal modification is that the equivalent wetting of the crystal surfaces is no longer assumed, since interactions between the crystal surfaces and the solution-state molecules are incorporated. These surface interactions have been investigated by using a grid-based systematic search method. The face-specific dissolution rates predicted by the extended binding energy model for ibuprofen in a 95% v/v ethanol–water solution and furosemide in an aqueous medium have been validated against the published experimental results and are in excellent agreement. This model is a step forward toward accurate predictions of the relative face-specific dissolution rates for a wide variety of faceted crystals in any dissolution medium.

A methodology is presented for predicting face-specific relative dissolution rates of single faceted crystals accounting for the inequivalent wetting by solvent. The predictions are validated against dissolution data for ibuprofen in ethanol−water and furosemide in aqueous medium with excellent agreement. It provides a step forward toward accurate predictions of dissolution rates for a variety of faceted crystals in different dissolution medium

A Couette cell flow device was designed, and an experimental procedure was developed to enable a quantitative study of the effects of fluid shear on secondary nucleation using a fixed seed crystal under controlled supersaturation, temperature, and flow conditions. This approach excludes mechanical impact, which is often considered to be the principal source of secondary nucleation, for example, through crystal attrition. We found that secondary nucleation rates of α-glycine in aqueous solutions induced by fluid shear were very significant and about 6 orders of magnitude higher than primary nucleation rates at the same conditions. Secondary nucleation rates per seed crystal were found to be about 1 order of magnitude lower compared with the magnetically stirred vials investigated previously, where a single seed crystal was freely moving, and thus, its mechanical impacts could not be ruled out. Computational fluid dynamics was used to calculate the wall shear stress along the surface of fixed seed crystals placed in the Couette cell gap at rotation rates between 100 and 600 rpm investigated here. This approach allows relating the secondary nucleation rate to the wall shear stress so that quantitative models can be developed to capture the effects of fluid shear on secondary nucleation kinetics. Such models will then facilitate scale-up and transfer of secondary nucleation kinetics between various equipment used in industrial crystallization processes.

The table of contents graphic shows the nucleation rates recorded in small, magnetically agitated vials compared with those from the Couette flow cell in which a seed was held in place and exposed to laminar shear. Secondary nucleation rates are much higher than primary nucleation rates in both cases, which indicates the significance of secondary nucleation induced by fluid shear.