Crystal Suspension Research Articles

Mechanisms of drug release from a melt-milled, poorly soluble drug substance

Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion.One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles.A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.

Multimaterial Digital-Light Processing of Metal-Organic Framework (MOF) Composites: A Versatile Tool for the Rapid Microfabrication of MOF-Based Devices.

Patterning Metal-Organic Frameworks (MOFs) is essential for their use in sensing, electronics, photonics, and encryption technologies. However, current lithography methods are limited in their ability to pattern more than two MOFs, hindering the potential for creating advanced multifunctional surfaces. Additionally, balancing design flexibility, simplicity, and cost often results in compromises. This study addresses these challenges by combining Digital-Light Processing (DLP) with a capillary-assisted stop-flow system to enable multimaterial MOF patterning. It demonstrates the desktop fabrication of multiplexed arbitrary micropatterns across cm-scale areas while preserving the MOF's pore accessibility. The ink, consisting of a MOF crystal suspension in a low volatile solvent, a mixture of high molecular weight oligomers, and a photoinitiator, is confined by capillarity in the DLP projection area and quickly exchanged using syringe pumps. The versatility of this method is demonstrated by the direct printing of a ZIF-8-based luminescent oxygen sensor, a 5-component dynamic information concealment method, and a PCN-224-based colorimetric sensor for amines, covering disparate pore and analyte sizes. The multi-MOF capabilities, simplicity, and accessibility of this strategy pave the way for the facile exploration of MOF materials across a wide range of applications, with the potential to significantly accelerate the design-to-application cycle of MOF-based devices.

Automated Continuous Crystallization Platform with Real-Time Particle Size Analysis via Laser Diffraction.

The fourth industrial revolution is gaining momentum in the pharmaceutical industry. However, particulate processes and suspension handling remain big challenges for automation and the implementation of real-time particle size analysis. Moreover, the development of antisolvent crystallization processes is often limited by the associated time-intensive experimental screenings. This work demonstrates a fully automated modular crystallization platform that overcomes these bottlenecks. The system combines automated crystallization, sample preparation, and immediate crystal size analysis via online laser diffraction (LD) and provides a technology for rapidly screening crystallization process parameters and crystallizer design spaces with minimal experimental effort. During the LD measurements, to avoid multiple scattering events, crystal suspension samples are diluted automatically. Multiple software tools, i.e., LabVIEW, Python, and PharmaMV, and logic algorithms are integrated in the platform to facilitate automated control of all the sensors and equipment, enabling fully automated operation. A customized graphical user interface is provided to operate the crystallization platform automatically and to visualize the measured crystal size and the crystal size distribution of the suspension. Antisolvent crystallization of ibuprofen, with ethanol as solvent and water with Soluplus (an additive) as antisolvent, is used as a case study. The platform is demonstrated for antisolvent crystallization of small ibuprofen crystals in a confined impinging jet crystallizer, performing automated preplanned user-defined experiments with online LD analysis.

Geochemical Thermometry of Ore-Bearing Gabbronorites from the Apophisis of the Yoko-Dovyren Massif: Composition, Amount of Olivine, and Conditions of Sulphide Saturation in the Parental Magma

The temperature and compositional parameters of the parental magma of the ore-bearing apophysis DV10 from the Yoko-Dovyren massif are estimated based on the results of thermodynamic modeling the equilibrium crystallization of melts of 24 samples, following the method of geochemical thermometry. Thermometric calculations were carried out using the COMAGMAT-5.3 program with a step of 0.5 mol. % to a maximum degree of crystallization 75–85% under oxygen fugacity controlled by the QFM buffer. The model order of mineral crystallization corresponds to the sequence: olivine (Ol) + + Cr-Al spinel (Spl) → plagioclase (Pl) → high-Ca pyroxene (Cpx) → orthopyroxene (Opx). Silicate-sulfide immiscibility was modeled to occur mostlybefore the onset of plagioclase crystallization, being consistent with sulfide saturation of the parental magma. The results of calculations demonstrate the convergence and intersection of the model liquid lines of descent at temperatures of about 1185°C. When applied to the average composition of the DV10 apophysis, this temperature indicates the existence of a suspension of the original crystals (52.1 wt. % cumulus olivine (Fo83.6), 2.3 wt. % plagioclase (An79.7), 0.24% clinopyroxene (Mg# 88.8), 1 wt. % aluminochromite (Cr# 0.62)) and about 0.2% sulfide liquid in a moderately magnesian melt (53.6 wt. % SiO2, 7.4 wt. % MgO). At that the solubility of sulfide sulfur (SCSS) was estimated to be 0.083 wt. %. This heterogeneous system had a viscosity of 4.71 log. units (Pa · s) and an integral density of 2929 kg/m3. Such rheological properties do not contradict the possibility of the migration and emplacement of the protocumulus mush from the main Dovyren chamber. However, a more probable scenario includes a localized accumulation of olivine in the trough-like part of the DV10 subchamber, which preceded or occurred in parallel to the accumulation of segregated sulfides.

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol

Background In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.

The influence of olivine settling on the formation of basaltic cumulates revealed by micro-tomography and numerical simulations

The speed at which crystals settle in magmatic reservoirs affects the solidification rate of magmas and their differentiation. Despite extensive prior work on the subject, most of our quantitative understanding of the process is still restricted to treating crystals as spherical particles and does not address the geometric complexities of natural crystals. Here, we use three-dimensional (3D) X-ray microcomputed tomography (X-μCT) observations on olivine crystals from Kīlauea Volcano (Hawai‘i) to document their highly intricate and variable geometries, and the textural growth relationships between the olivine crystals and their inclusions (melt, spinel, and fluid/vapor bubbles). Olivine crystals generally have clustered polyhedral or skeletal shapes, which reflect variable magmatic conditions (or growth rates) during their formation. The cumulative presence of spinel, melt, fluid, and vapor inclusions affects the density of the host crystals by up to 6% relative, and thus plays a limited role on modifying crystal settling rate. In contrast, the overall crystal shape plays a major role. We performed numerical simulations employing a finite element method to investigate the effect of crystal morphology on settling rate and the evolution of the particle volume fraction in a magmatic convective layer. We show that for all olivine geometries investigated, the settling velocity is highest when the long axis of the crystal is aligned with the flow direction of the melt. Increasing the aspect ratio of the olivine tends to decrease its settling velocity and results in an increase in the influence of its orientation on the terminal velocity (UT). Extrapolation of the simulation results to variable particle volume fractions (Φ = 0–0.5) indicates high crystal settling rates (UT = ∼9.7 × 10−6–1.4 × 10−5 m/s) that are used to estimate the timescales for the formation of olivine cumulates in natural melt-dominated basaltic systems. The formation of olivine cumulates is therefore rapid, potentially leading to the accumulation of a crystal layer at the bottom, where the frictional contacts between the crystals exert a rheological lock-up acting against further convection. Crystal accumulation in the locked layer (parametrized with the solid/liquid volume ratio in the reservoir) is a function of the reservoir size and crystal fraction, and takes a few years in small reservoirs (<1 km thick) and a few decades in larger reservoirs (several kms thick). We propose a calibration of olivine suspension timescales for mafic magma reservoirs (based on the knowledge of the particle volume fraction, reservoir height, and olivine morphology). This calibration is used to estimate the rate of cumulate build-up, and can help interpret crystal size distributions in the framework of crystal suspension times.

Bottom-up production of injectable itraconazole suspensions using membrane technology

Bottom-up production of active pharmaceutical ingredient (API) crystal suspensions offers advantages in surface property control and operational ease over top-down methods. However, downstream separation and concentration pose challenges. This proof-of-concept study explores membrane diafiltration as a comprehensive solution for downstream processing of API crystal suspensions produced via anti-solvent crystallization. It involves switching the residual solvent (N-methyl-2-pyrrolidone, NMP) with water, adjusting the excipient (d-α-Tocopherol polyethylene glycol 1000 succinate, TPGS) quantity, and enhancing API loading (solid concentration) in itraconazole crystal suspensions. NMP concentration was decreased from 9 wt% to below 0.05 wt% (in compliance with European Medicine Agency guidelines), while the TPGS concentration was decreased from 0.475 wt% to 0.07 wt%. This reduced the TPGS-to-itraconazole ratio from 1:2 to less than 1:50 and raised the itraconazole loading from 1 wt% to 35.6 wt%. Importantly, these changes did not adversely affect the itraconazole crystal stability in suspension. This study presents membrane diafiltration as a one-step solution to address downstream challenges in bottom-up API crystal suspension production. These findings contribute to optimizing pharmaceutical manufacturing processes and hold promise for advancing the development of long-acting API crystal suspensions via bottom-up production techniques at a commercial scale.

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol

Background In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.

Tailoring the use of excipients in bottom-up production of naproxen crystal suspensions via membrane technology

Long-acting crystal suspensions of active pharmaceutical ingredients (API) mostly comprised of an API, a suspension media (water) and excipients and provide sustained API release over time. Excipients are crucial for controlling particle size and to achieve the stability of the API crystals in suspension. A bottom-up process was designed to produce long-acting crystal suspensions whilst investigating the excipient requirements during the production process and the subsequent storage. PVP K30 emerged as the most effective excipient for generating stable naproxen crystals with the desired size of 1 to 15 μm, using ethanol as solvent and water as anti-solvent. Calculations, performed based on the crystal properties and assuming complete PVP K30 adsorption on the crystal surface, revealed lower PVP K30 requirements during storage compared to initial crystal generation. Consequently, a membrane-based diafiltration process was used to determine and fine-tune PVP K30 concentration in the suspension post–crystallization. A seven-stage diafiltration process removed 98 % of the PVP K30 present in the suspension thereby reducing the PVP-to-naproxen ratio from 1:2 to 1:39 without impacting the stability of naproxen crystals in suspension. This work provides insights into the excipient requirements at various production stages and introduce the membrane-based diafiltration for precise excipient control after crystallization.

Cholesteric Spherical Reflectors with Tunable Color from Single-Domain Cellulose Nanocrystal Microshells.

The wavelength- and polarization-selective Bragg reflection of visible light exhibited by films produced by drying cholesteric liquid crystal (CLC) suspensions of cellulose nanocrystals (CNCs) render these biosourced nanoparticles highly potent for many optical applications. While the conventionally produced films are flat, the CLC-derived helical CNC arrangement would acquire new powerful features if given spherical curvature. Drying CNC suspension droplets does not work, because the onset of kinetic arrest in droplets of anisotropic colloids leads to severe buckling and loss of spherical shape. Here, these problems are avoided by confining the CNC suspension in a spherical microshell surrounding an incompressible oil droplet. This prevents buckling, ensures strong helix pitch compression, and produces single-domain cholesteric spherical reflector particles with distinct visible color. Interestingly, the constrained shrinkage leads to spontaneous puncturing, leaving every particle with a single hole through which the inner oil phase can be extracted for recycling. By mixing two different CNC types at varying fractions, the retroreflection color is tuned throughout the visible spectrum. The new approach adds a versatile tool in the quest to utilize bioderived CLCs, enabling spherically curved particles with the same excellent optical quality and smooth surface as previously obtained only in flat films.

A phononic crystal suspension for vibration isolation of acoustic loads in underwater gliders

Currently, it is a common practice to apply underwater gliders with acoustic loads for hydroacoustic detection, but the self-noise of the vehicle inevitably interferes with signal acquisition. In this study, a novel suspension is designed based on phononic crystals to realize vibration isolation of the acoustic loads in underwater gliders. The vibration properties of finite-period phononic crystals with different layouts of unit cells are studied by analyzing the attenuation zones, and the three-period phononic crystal with prolonged metal ends is determined to be the optimal structure of the suspension. Moreover, the effect of physical parameters on the underwater attenuation zones of the proposed suspension is further investigated through acoustic-structure coupling, resulting in the formation of a design scheme for the suspension. A vibration test is performed in an anechoic pool, which reveals that the phononic crystal suspension has a stable vibration isolation effect at 120–5000 Hz and achieves a maximum vibration isolation of about 7 dB compared with the original structure. The results in the present work provide a theoretical reference for applying phononic crystals for vibration isolation in underwater vehicles.

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol.

In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.

Hard Gelatin Capsules Containing Hot Melt Extruded Solid Crystal Suspension of Carbamazepine for improving dissolution: Preparation and In vitro Evaluation.

Aqueous solubility is one of the key parameters for achieving the desired drug concentration in systemic circulation for better therapeutic outcomes. Carbamazepine (CBZ) is practically insoluble in water, is a BCS class II drug, and exhibits dissolution-dependent oral bioavailability. This study explored a novel application of hot-melt extrusion in the manufacture and development of a thermodynamically stable solid crystal suspension (SCS) to improve the solubility and dissolution rate of CBZ. The SCSs were prepared using sugar alcohols, such as mannitol or xylitol, as crystalline carriers. The drug-sugar blend was processed by hot melt extrusion up to 40 % (w/w) drug loading. The extruded SCS was evaluated for drug content, saturation solubility, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), in vitro release, and stability studies. The physicochemical characterization revealed the highly crystalline existence of pure drug, pure carriers, and extruded SCS. FTIR analysis did not reveal any physical or chemical incompatibilities between the drug and sugar alcohols and showed a homogeneous CBZ distribution within respective crystalline carriers. The SEM micrographs of the solidified SCS revealed the presence of approximately 100 μm crystalline agglomerates. In vitro dissolution and solubility studies showed that the CBZ dissolution rate and solubility were improved significantly from both crystalline carriers for all tested drug loads. The SCSs showed no significant changes in drug content, in vitro release profiles, and thermal characteristics over 3 months of storage at accelerated stability conditions (40±2°C/75±5% RH). As a result, it can be inferred that the SCS strategy can be employed as a contemporary alternative technique to improve the dissolution rate of BCS class II drugs via HME technology.

Acoustomicrofluidic Defect Engineering and Ligand Exchange in ZIF-8 Metal-Organic Frameworks.

A way through which the properties of metal-organic frameworks (MOFs) can be tuned is by engineering defects into the crystal structure. Given its intrinsic stability and rigidity, however, it is difficult to introduce defects into zeolitic imidazolate frameworks (ZIFs)-and ZIF-8, in particular-without compromising crystal integrity. In this work, it is shown that the acoustic radiation pressure as well as the hydrodynamic stresses arising from the oscillatory flow generated by coupling high frequency (MHz-order) hybrid surface and bulk acoustic waves into a suspension of ZIF-8 crystals in a liquid pressure transmitting medium is capable of driving permanent structural changes in their crystal lattice structure. Over time, the enhancement in the diffusive transport of guest molecules into the material's pores as a consequence is shown to lead to expansion of the pore framework, and subsequently, the creation of dangling-linker and missing-linker defects, therefore offering the possibility of tuning the type and extent of defects engineered into the MOF through the acoustic exposure time. Additionally, the practical utility of the technology is demonstrated forone-pot, simultaneous solvent-assisted ligand exchange under ambient conditions, for sub-micron-dimension ZIF-8 crystals and relatively large ligands-more specifically 2-aminobenzimidazole-without compromising the framework porosity or overall crystalstructure.

Membrane-Based Solvent Exchange Process for Purification of API Crystal Suspensions.

Bottom-up approaches to producing aqueous crystal suspensions of active pharmaceutical ingredients (APIs), such as anti-solvent crystallisation, are gaining interest as they offer better control over surface properties compared to top-down approaches. However, one of the major challenges that needs to be addressed is the removal of organic solvents after the crystallisation step due to strict limitations regarding human exposure. Within this work, we investigated a process concept for the removal of solvent (i.e., ethanol) from the API crystal suspension using membrane-based diafiltration. A four-stage diafiltration process successfully reduced the ethanol concentration in the API (here, naproxen) crystal suspension below 0.5 wt% (the residual solvent limit as per ICH guidelines) with a water consumption of 1.5 g of added water per g of feed. The solvent exchange process had no negative influence on the stability of the crystals in suspension, as their size and polymorphic form remained unchanged. This work is a step towards the bottom-up production of API crystal suspension by applying solvent/anti-solvent crystallisation. It provides the proof of concept for establishing a process of organic solvent removal and offers an experimental framework to serve as the foundation for the design of experiments implementing a solvent exchange in API production processes.

X-ray-Induced Heating in the Vicinity of the X-ray Interaction Point

When X-rays pass through a material, radiation damage occurs, and heat is generated at the X-ray interaction point, which can then be transferred around the X-ray irradiation site. This X-ray-induced heat transfer can affect the temperature of the sample and consequently the experimental environment in serial crystallography (SX) experiments. Here, we investigated radiation damage and measured the level of heating in the vicinity of the X-ray interaction point. In our experimental setup, when water, crystallization solution, and crystal suspension in a glass tube were exposed to X-rays, a temperature increase of approximately 1.0 °C occurred in the vicinity of the X-ray interaction point, with the heat generated by both the sample and the capillary. When Cu and Al/Zn plates were exposed to X-rays, the temperature around the X-ray exposure point increased by approximately 0.3 and 0.4 °C, respectively. The range of temperature rise decreased as the distance from the X-ray exposure point on the Al plate increased. The heat generated by the X-rays and the rise of the heat could be reduced by discontinuously transmitting the X-rays using the shutter. Our results provide useful information for obtaining more accurate experimental parameters.

Field-Induced Stratification of Goethite Particles in Nematic Matrix

Within the continuum theory, the stratification of colloidal goethite particles in a nematic matrix induced by magnetic and gravitational fields has been studied. The case of a magnetically compensated suspension, which is a liquid crystal analogue of an antiferromagnet, is considered. For a twist structure, the spatial distributions of the fields of the director of the liquid crystal medium and the dispersed phase are studied. The distributions of goethite impurity particles over the layer thickness are calculated for different values of the magnetic field. The obtained equations of orientational and magnetic equilibrium of suspensions of goethite particles in a nematic have a general form and, in limiting cases, can be used to describe liquid crystal suspensions of anisometric ferromagnetic particles and carbon nanotubes.

Single-Crystalline Imine-Linked Two-Dimensional Covalent Organic Frameworks Separate Benzene and Cyclohexane Efficiently.

Two-dimensional (2D) covalent organic frameworks (COFs) are composed of structurally precise, permanently porous, layered macromolecular sheets, which are traditionally synthesized as polycrystalline solids with crystalline domain lengths smaller than 100 nm. Here, we polymerize imine-linked 2D COFs as suspensions of faceted single crystals in as little as 5 min at moderate temperature and ambient pressure. Single crystals of two imine-linked 2D COFs were prepared, consisting of a rhombic 2D COF (TAPPy-PDA) and a hexagonal 2D COF (TAPB-DMPDA). The sizes of TAPPy-PDA and TAPB-DMPDA crystals were tuned from 720 nm to 4 μm and 450 nm to 20 μm in width, respectively. High-resolution transmission electron microscopy revealed that the COF crystals consist of layered, 2D polymers comprising single-crystalline domains. Continuous rotation electron diffraction resolved the unit cell and crystal structure of both COFs, which are single-crystalline in the a-b plane but disordered in the stacking c dimension. Single crystals of both COFs were incorporated into gas chromatography separation columns and exhibited unusual selective retention of cyclohexane over benzene, with single-crystalline TAPPy-PDA significantly outperforming single-crystalline TAPB-DMPDA. Polycrystalline TAPPy-PDA exhibited no separation, while polycrystalline TAPB-DMPDA exhibited poor separation and the opposite order of elution, retaining benzene more than cyclohexane, indicating the importance of improved material quality for COFs to exhibit properties that derive from their precise, crystalline structures. This work represents the first example of synthesizing imine-linked 2D COF single crystals at ambient pressure and short reaction times and demonstrates the promise of high-quality COFs for molecular separations.

Mechanism of chirality conversion of crystals by Viedma ripening and temperature cycling

Grinding chiral crystals in a saturated solution (Viedma ripening) and changing temperature of crystal suspension (temperature cycling) have become promising methods to convert chirality of crystals, and thereby chirality of molecules under racemizing condition of molecules. We discuss mechanisms of these processes by reviewing proposed mathematical models such as mass reaction rate equations, Becker–Döring models, various Monte Carlo models, and population balance models.

Fixed-target serial crystallography at the Structural Biology Center.

Serial synchrotron crystallography enables the study of protein structures under physiological temperature and reduced radiation damage by collection of data from thousands of crystals. The Structural Biology Center at Sector 19 of the Advanced Photon Source has implemented a fixed-target approach with a new 3D-printed mesh-holder optimized for sample handling. The holder immobilizes a crystal suspension or droplet emulsion on a nylon mesh, trapping and sealing a near-monolayer of crystals in its mother liquor between two thin Mylar films. Data can be rapidly collected in scan mode and analyzed in near real-time using piezoelectric linear stages assembled in an XYZ arrangement, controlled with a graphical user interface and analyzed using a high-performance computing pipeline. Here, the system was applied to two β-lactamases: a class D serine β-lactamase from Chitinophaga pinensis DSM 2588 and L1 metallo-β-lactamase from Stenotrophomonas maltophilia K279a.