Crystal Polymorphism Research Articles

Unknown crystal-like phases formed in an imidazolium ionic liquid: A metadynamics simulation study.

Crystal polymorphism of complex liquids plays a crucial role in industrial crystallization, food technology, pharmaceuticals, and materials engineering. However, the experimental identification of unknown crystal structures can be challenging, particularly for high-viscosity complex liquids, such as ionic liquids (ILs). In this study, we performed a molecular dynamics simulation coupled with metadynamics to investigate an imidazolium IL (1-alkyl-3-methylimidazolium hexafluorophosphates). The simulation employed two distinct radial-distribution functions, represented by Gaussian window functions as collective variables, and revealed at least two crystal-like phases distinct from the known α and β crystal phases typically formed by this IL. Additionally, the simulation unveiled a unique phase characterized by the ordered spatial arrangement of anion aggregations. These crystal-like and unique phases emerged regardless of the potential used. The simulation methodology presented here is broadly applicable for exploring unknown phases in complex systems and contributes to the design of functional materials, such as porous ILs for gas molecule capture and separation.

Radiation-enhanced crystallization of amorphous Nb2O5 films according to TEM with in situ video recording

Amorphous films are formed on substrates at room temperature in the process of anodic oxidation of niobium foil. The studies were carried out using methods of electron diffraction and “in situ” transmission electron microscopy (TEM) with video recording of structural changes. It was found that electron beam irradiation of the film with a dose rate (4–7)·104 e−/Å2·s inside the column of the electron microscope causes its layer polymorphous crystallization (LPC) with the formation of Nb2O5 crystals with hexagonal lattice. The dimensionless parameter of the relative crystallization length δ0≈ 5000 − 7000. The dependence on time of the crystal diameter is described by a power function with exponents of 1.55, 1.1 and 1.3. According to this the dependence of the fraction of the crystalline phase on time is described by a power function with exponents of 3.1, 2.2 and 2.6. This non-quadratic nature is explained with the formation of a domain superstructure in the low-temperature modification of α-Nb2O5 and phenomenon of polyamorphism in amorphous films.

High-Voltage Spinel Cathode Materials: Navigating the Structural Evolution for Lithium-Ion Batteries.

High-voltage LiNi0.5Mn1.5O4 (LNMO) spinel oxides are highly promising cobalt-free cathode materials to cater to the surging demand for lithium-ion batteries (LIBs). However, commercial application of LNMOs is still challenging despite decades of research. To address the challenge, the understanding of their crystallography and structural evolutions during synthesis and electrochemical operation is critical. This review aims to illustrate and to update the fundamentals of crystallography, phase transition mechanisms, and electrochemical behaviors of LNMOs. First, the research history of LNMO and its development into a LIB cathode material is outlined. Then the structural basics of LNMOs including the classic and updated views of the crystal polymorphism, interconversion between the polymorphs, and structure-composition relationship is reviewed. Afterward, the phase transition mechanisms of LNMOs that connect structural and electrochemical properties are comprehensively discussed from fundamental thermodynamics to operando dynamics at intra- and inter-particle levels. In addition, phase evolutions during overlithiation as well as thermal-/electrochemical-driven phase transformations of LNMOs are also discussed. Finally, recommendations are offered for the further development of LNMOs as well as other complex materials to unlock their full potential for future sustainable and powerful batteries.

Application of Different Animal Fats as Solvents to Extract Carotenoids and Capsaicinoids from Sichuan Chili.

Inspired by the proved dissolving power of vegetable oils for non-polar and low-polar natural compounds, animal fats with triglycerides as the major components were investigated as food-grade solvents in this study for the simultaneous extraction of carotenoids and capsaicinoids from Sichuan chili. The dissolving power of lard, beef tallow, chicken fat and basa fish oil in the extraction of er jing tiao chili was firstly compared, where animal oils with worse extraction ratios for carotenoids (0.79 mg/g in average) performed better for the extraction of capsaicinoids (0.65 mg/g in average). Furthermore, the solvent effect of animal fats on the oleo-extracts was evaluated in terms of fatty acid composition, oil quality indexes, crystal polymorphism, melting and crystallization behaviors, where no significant differences were observed between animal fats before and after extraction. The oxidative stability of animal fats could be 1.02- up to 2.73-fold enhanced after extraction and the pungency degree could reach the same spicy level as commercial hotpot oil. In addition, the Hansen solubility parameters of solvents and solutes were predicted for further theoretical miscibility study, which helps to make a better comprehension of the dissolving mechanism behind such oleo-extraction. Overall, animal fats demonstrated their considerable solvent power for extracting carotenoids and capsaicinoids simultaneously from Sichuan chili, which showed significant potential for developing a novel Sichuan spicy hotpot oil with enhanced flavor and stability.

Liquid Crystal Dimers and the Twist-Bend Phases: Non-Symmetric Dimers Consisting of Mesogenic Units of Differing Lengths.

The syntheses and characterisation of the 4-[{[4-({n-[4-(4-cyanophenyl)phenyl]-n-yl}oxy)phenyl]-methylidene}amino]phenyl-4-alkoxybenzoates (CBnOIBeOm) are reported with n=8 and 10 and m=1-10. The two series display fascinating liquid crystal polymorphism. All twenty reported homologues display an enantiotropic nematic (N) phase at high temperature. When the length of the spacer (n) is greater than that of the terminal chain (m), the twist-bend nematic (NTB) phase is observed at temperatures below the N phase. As the length of the terminal chain is increased and extends beyond the length of the spacer up to three smectic phases are observed on cooling the N phase. One of these smectic phases has been assigned as the rare twist-bend smectic C subphase, the SmCTB-α phase. In all the smectic phases, a monolayer packing arrangement is seen, and this is attributed to the anti-parallel associations of the like mesogenic units.

Sustainable deep eutectic solvents induced the polymorph selectivity and high purification efficiency

Deep eutectic solvents (DESs), as modern green solvents, have been examined as sustainable crystallization media in recent years. Nevertheless, their roles in affecting nucleation and polymorph control of crystal materials are still poorly understood. Herein, we report the use of DES for controlling polymorph crystallization and investigate systematically the mechanism of DES solvent characteristics on polymorph selectivity. Concomitant crystallization of sulfathiazole (STZ) polymorphs has been widely reported in organic solvents, while we found DES can improve its polymorph selectivity significantly. Pure forms II and IV were selectively and rapidly obtained from solvents containing [thymol][fatty acid] and [thymol][coumarin] DESs, respectively. The microstructural changes of DES exhibited dynamic regulatory effect on STZ polymorph selectivity. Analysis of 1H NMR, viscosity and computational simulations revealed that the DES hydrogen-bonding network structures were preserved for DES contents above 50 wt% in binary solvents, which affected the nucleation kinetics of STZ and its molecular assembly during crystallization process. Further mechanistic investigations suggested that DES hydrogen-bonding network structures exerted confinement effect and nucleation-templating effect through DES-solute interactions (hydrogen-bonding and π-π stacking interactions for [thymol][fatty acid] and [thymol][coumarin] systems, respectively), which limited the motion of solute molecules and delayed nucleation rate as well as induced the STZ nucleation toward specific orientations, thus achieving polymorph selectivity. In addition, DESs could be recycled and exhibited good reproducibility in achieving STZ polymorph purification. This study offers a sustainably effective strategy for polymorph purification of crystalline materials and promotes advance the fundamental understanding of DES solvent characteristics on polymorph control.

In situ analyses of crystallization behavior of 1,2,3-tripalmitoyl glycerol under static and dynamic thermal conditions

The crystallization behavior of 1,2,3-tripalmitoyl glycerol or PPP using differential scanning calorimetry (DSC), thermo-optical polarized light microscopy and in situ synchrotron radiation X-ray diffraction (SR-XRD) techniques was precisely examined under static isothermal and dynamic thermal treatments, and the results were compared with preceding studies. PPP was rapidly (15 °C min−1) cooled to target temperatures (from 40 to 59 °C) to determine the precise moment at which crystallization was initiated. Once crystallization ceased, polymorphic transformation and melting were analyzed during subsequent heating. α form was crystallized during isotherms from 40 to 46 °C, temperature at which it coexisted with β′ phase. The latter was solely formed from 47 to 53 °C, and polymorphic crystallization was directed to obtain exclusively most stable β at 54 °C and higher temperatures. Nucleation time values for the α, β′ and β polymorphs exhibited exponential growth type, and a good correlation was found between data obtained by DSC and SR-XRD. Dynamic experiments were based on the use of high (15 °C min−1), intermediate (2 °C min−1) and low (0.5 and 0.1 °C min−1) cooling and heating rates. Thermo-optical polarized light microscopy experiments also provided valuable information on microstructural changes occurring during polymorphic modifications. Less stable forms predominated at high cooling rates, whereas lower velocities leaded the polymorphic crystallization to obtain more stable forms.

Highly efficient in crystallo energy transduction of light to work.

Various mechanical effects have been reported with molecular materials, yet organic crystals capable of multiple dynamic effects are rare, and at present, their performance is worse than some of the common actuators. Here, we report a confluence of different mechanical effects across three polymorphs of an organic crystal that can efficiently convert light into work. Upon photodimerization, acicular crystals of polymorph I display output work densities of about 0.06-3.94 kJ m-3, comparable to ceramic piezoelectric actuators. Prismatic crystals of the same form exhibit very high work densities of about 1.5-28.5 kJ m-3, values that are comparable to thermal actuators. Moreover, while crystals of polymorph II roll under the same conditions, crystals of polymorph III are not photochemically reactive; however, they are mechanically flexible. The results demonstrate that multiple and possibly combined mechanical effects can be anticipated even for a simple organic crystal.

Shape-Dependent Optical Waveguides and Low-Threshold Lasers from Polymorphic Two-Dimensional Organic Single Crystals.

Organic single crystals (OSCs) with uniform morphologies and highly ordered molecular aggregations are promising for high-performance optoelectronic devices, such as organic solid-state lasers (OSSLs), organic light-emitting transistors (OLETs), and organic light-emitting diodes (OLEDs). However, manipulating OSC morphologies and aggregation is challenging. In this study, we synthesized two-dimensional (2D) OSCs of 4,4'-bis[(N-carbazole)styryl]biphenyl (BSBCz) in hexagonal and parallelogram microplate (H-MP and P-MP) forms. Both types exhibit H-aggregation in the 2D plate plane but with different molecular transition dipole moment (TDM) orientations. This leads to different photon coupling modes with H-MP and P-MP microcavities. H-MPs enable isotropic 2D-waveguiding, forming whispering gallery mode (WGM) resonators, while P-MPs create unidirectional waveguiding, forming Fabry-Pérot mode (FP) resonators. These resonators can generate low-threshold laser emissions at 467 and 473 nm, respectively, and exhibit superior lasing stability with a half-life exceeding 2 h. Our BSBCz microplate OSCs are attractive candidates to combine controlled organic microcavities with photon transporting for realizing future integrated optoelectronic devices.

Impact of nanoconfinement on the physical state and conductivity mechanisms of a 2-picolinium ionic liquid crystal

Hybrid solid-like materials prepared from the incorporation of liquid-like ionic conductors into nanoporous matrices could represent an advantage for a variety of electronic applications. Aiming to obtain such materials, three composites of the polymorphic ionic liquid crystal (ILC) 1-hexadecyl-2-methylpyridinium bromide ([C16-2-Pic][Br]), loaded in the mesoporous inorganic silica SBA-15 (∼6.8 nm in pore diameter), were prepared at guest–host weight fractions of ∼ 40, 60 and 80% (w/w) and investigated by different techniques: ATR-FTIR, BET, TGA, XRD and DSC. Complete amorphisation was achieved for the 40 and 60% composites, while the 80% preparation was stabilised in the low-T morph of native C16, being in the liquid state at room temperature. Furthermore, through Dielectric Relaxation Spectroscopy, the ionic conductivity of the three hybrid materials was characterised, allowing to deconvolute this property in a pure ohmic contribution (conductivity I) and the overlapping of ac − dc transition with interfacial polarisation resulting from the coexistence of the ionic liquid and the quasi-insulating inorganic matrix (conductivity II). From –20 to 20 °C, the conductivity and the corresponding charge migration are faster in all composites relative to the neat ILC, as deduced from the inferior radii of Nyquist arcs. The 60% preparation stood out from the other materials, exhibiting direct conductivity unaffected by electrode polarisation over a larger T-range, leading to the assumption of a nearly continuous silica-mediated charge migration pathway, which is never reached for the 40% composite, while, in the 80% preparation, some C16 deposits on the outer surface of the pores. Incorporation into the silica matrix proved to be a good strategy for the production of cost-efficient materials with long-term stabilisation of the ionic liquid in a single phase over a large range of temperatures, enabling the prediction of flow and conductive properties.

Polymorphism and White Light Emission of 1‐Bromo‐3,5,7‐triphenyladamantane Compared with 1,3,5,7‐Tetraphenyladamantane

AbstractHere we report our investigation of 1‐bromo‐3,5,7‐triphenyladamantane (1) and the elucidation of polymorphic crystals (1 A and 1 B) using single crystal X‐ray diffraction. In the monoclinic crystal system of 1 A (P21/n), we observed CH–π interactions, while Br⋅⋅⋅Br interactions are absent. Conversely, the Br⋅⋅⋅Br interactions are an apparent factor in the formation of the monoclinic crystal system of 1 B (R ). We compare our findings with 1,3,5,7‐tetraphenyladamantane (2), characterized by numerous CH–π interactions in the solid. Computational analyses were employed to investigate the interactions within the characteristic dimers present in the unit cells of 1 A and 1 B, including visualization of noncovalent interactions and the use of the atoms‐in‐molecules approach as well as MO analyses. These support the notion of London dispersion (LD) dimer‐dimer interactions in 1 A between the phenyl moieties, whereas 1 B exhibits additional dimer‐dimer Br⋅⋅⋅Br contacts. In contrast, the crystals of 2 are exclusively held together by CH–π stacking LD interactions, a feature absent in the polymorphs of 1. Both polymorphic forms of 1 emit white light when subjected to 900 nm continuous wave laser irradiation, displaying a subtle blue shift compared to 2. The absence of CH–π stacking interactions between the dimers of 1 causes a small red‐shift in the emission spectrum.

Diverse crystalline protein scaffolds through metal-dependent polymorphism.

As protein crystals are increasingly finding diverse applications as scaffolds, controlled crystal polymorphism presents a facile strategy to form crystalline assemblies with controllable porosity with minimal to no protein engineering. Polymorphs of consensus tetratricopeptide repeat proteins with varying porosity were obtained through co-crystallization with metal salts, exploiting the innate metal ion geometric requirements. A single structurally exposed negative amino acid cluster was responsible for metal coordination, despite the abundance of negatively charged residues. Density functional theory calculations showed that while most of the crystals were the most thermodynamically stable assemblies, some were kinetically trapped states. Thus, crystalline porosity diversity is achieved and controlled with metal coordination, opening a new scope in the application of proteins as biocompatible protein-metal-organic frameworks (POFs). In addition, metal-dependent polymorphic crystals allow direct comparison of metal coordination preferences.

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

AbstractContinuous crystallization of pharmaceuticals has been in the center of attention during the past two decades, with a more focus on the large‐scale production of active pharmaceutical ingredients. The increasing demand for pharmaceuticals requires high‐throughput production of drug crystals with different solubilities, stabilities, shapes, habits, polymorphs, and size distributions. With numerous advantages including low cost, ease of scale‐up, and superior control over polymorph and size distribution of drug crystals, antisolvent crystallization is one of the most promising crystallization methods recently attempted. However, it fails to deliver the required characteristic where the crystal systems tend to grow and for the preparation of metastable polymorphs. This review focuses on the most recent efforts to tackle these drawbacks by coupling antisolvent crystallization with cooling, supercritical‐assisted, microfluidics‐assisted, and membrane‐assisted crystallization. This systematic review aims to provide a concise summary of each coupled antisolvent technique and their positive and negative aspects. This review can be used as a guideline for pharmacist, biologists, and chemists, who are interested in the crystal engineering of pharmaceuticals to pave the way for further developments in this field.

Relationship between crystal structure and optical properties in light blue- and green-emitting crystal polymorphs of butyl group-substituted thiophene/phenylene co-oligomer: Fabrication of crystals and their lasing properties

Light-blue (monoclinic) and green (orthorhombic) crystal polymorphs comprising a butyl group-substituted thiophene/phenylene co-oligomer, BP1T-Bu, were prepared by varying the crystal growth conditions with a solution-growth technique. The light-blue- and green-emitting crystals exhibited Fabry–Pérot lasing above the excitation density of 204 and 277 μJ/cm2 based on high group refractive indices and quality factors, respectively. The higher threshold in the green-emitting crystal originates from the lower absorption efficiency of the excitation light, in addition to the lower amount of absorption owing to the smaller thickness of the crystal.

Crystal Polymorphism and Phase Transition of Isodimorphic Copolyamides Based on Even–Even and Odd–Even Comonomer Units: Synergistic Effects of Copolymer Composition and Crystallization Temperature

Crystal Polymorphism and Phase Transition of Isodimorphic Copolyamides Based on Even–Even and Odd–Even Comonomer Units: Synergistic Effects of Copolymer Composition and Crystallization Temperature

Crystal Polymorph Search in the NPT Ensemble via a Deposition/Sublimation Alchemical Path.

The formulation of active pharmaceutical ingredients involves discovering stable crystal packing arrangements or polymorphs, each of which has distinct pharmaceutically relevant properties. Traditional experimental screening techniques utilizing various conditions are commonly supplemented with in silico crystal structure prediction (CSP) to inform the crystallization process and mitigate risk. Predictions are often based on advanced classical force fields or quantum mechanical calculations that model the crystal potential energy landscape but do not fully incorporate temperature, pressure, or solution conditions during the search procedure. This study proposes an innovative alchemical path that utilizes an advanced polarizable atomic multipole force field to predict crystal structures based on direct sampling of the NPT ensemble. The use of alchemical (i.e., nonphysical) intermediates, a novel Monte Carlo barostat, and an orthogonal space tempering bias combine to enhance the sampling efficiency of the deposition/sublimation phase transition. The proposed algorithm was applied to 2-((4-(2-(3,4-dichlorophenyl)ethyl)phenyl)amino)benzoic acid (Cambridge Crystallography Database Centre ID: XAFPAY) as a case study to showcase the algorithm. Each experimentally determined polymorph with one molecule in the asymmetric unit was successfully reproduced via approximately 1000 short 1 ns simulations per space group where each simulation was initiated from random rigid body coordinates and unit cell parameters. Utilizing two threads of a recent Intel CPU (a Xeon Gold 6330 CPU at 2.00 GHz), 1 ns of sampling using the polarizable AMOEBA force field can be acquired in 4 h (equating to more than 300 ns/day using all 112 threads/56 cores of a dual CPU node) within the Force Field X software (https://ffx.biochem.uiowa.edu). These results demonstrate a step forward in the rigorous use of the NPT ensemble during the CSP search process and open the door to future algorithms that incorporate solution conditions using continuum solvation methods.

Linearly-Changed Thermal Behavior and Depressed Brill Transition in Long-Chain Polyamides Substituted by Methyl Side Groups.

Side substitution is an effective way of functionalizing and modifying the properties of polyamides. Meanwhile, side substitution would significantly influence the crystallization kinetics and polymorphic phase transition of polyamides, which, however, has not been well elucidated. Herein, we synthesized the side-substituted long-chain polyamides with various content of methyl pendent groups and investigated their crystallization and phase transition behaviors. We find that the thermal parameters of side-substituted polyamides vary linearly with the side group content, analogous to the isomorphic crystallization of random copolymers. All the solution-crystallized polyamides experience the α-γ Brill transition during heating, with the Brill transition temperature linearly decreasing as the side group content increases. Intriguingly, the γ-α transition of polyamides during cooling is suppressed with the presence of side methyl groups due to the difficulty in H-bond reorganization and gauche-trans conformational changes. This work has demonstrated the critical role of side substitution in the polymorphic crystallization and phase transition of long-chain polyamides.

Confined liquid crystallization governed by electric field for API crystal polymorphism screening and massive preparation

Active pharmaceutical ingredients (APIs) crystal preparation is a significant issue for the pharmaceutical development attributed to the effect on anti-inflammatory, anti-bacteria, and anti-viral, etc. While, the massive preparation of API crystal with high polymorphism selectivity is still a pendent challenge. Here, we firstly proposed a criterion according to the molecular aggregation, molecular orientation, and hydrogen bond energy between INA molecules from molecular dynamics (MD) simulations, which predicted the hydrogen bond architecture in crystal under different electric fields, hinting the recognition of crystal polymorphism. Then, an electric field governing confined liquid crystallization was constructed to achieve the INA crystal polymorphism screening relying on the criterion. Further, magnifying confined liquid volume by 5000 times from 1.0 μL to 5.0 mL realized the massive preparation of INA crystal with high polymorphic purity (>98.4%), giving a unique pathway for crystal engineering and pharmaceutical industry on the development of innovative and generic API based drugs.

Crystallization of molecular layers produced under confinement onto a surface

It is well known that molecules confined very close to a surface arrange into molecular layers. Because solid-liquid interfaces are ubiquitous in the chemical, biological and physical sciences, it is crucial to develop methods to easily access molecular layers and exploit their distinct properties by producing molecular layered crystals. Here we report a method based on crystallization in ultra-thin puddles enabled by gas blowing, which allows to produce molecular layered crystals with thickness down to the monolayer onto a surface, making them directly accessible for characterization and further processing. By selecting four molecules with different types of polymorphs, we observed exclusive crystallization of polymorphs with Van der Waals interlayer interactions, which have not been observed with traditional confinement methods. In conclusion, the gas blowing approach unveils the opportunity to perform materials chemistry under confinement onto a surface, enabling the formation of distinct crystals with selected polymorphism.

Drug Polymorphism: An Important Pre-formulation Tool in the Formulation Development of a Dosage Form

Abstract: Polymorphism permits solids to have two or multiple crystal structures with varying orientations or conformations, and polymorph drug dissolution and solubility vary. Polymorphism influences drug efficacy, bioavailability and toxicity. Various parameters can regulate polymorph crystallization, including supersaturation phase, temperature, stirring rate, solvent addition rate, seed crystal, additives and pH. To characterize and monitor polymorphs, various analytical approaches are available, including powder X-Ray diffraction / X-Ray diffraction (PXRD/XRD), also called as Gold Standard method, differential scanning calorimetry (DSC), Infrared spectroscopy (IR), and microscopical studies. To prevent polymorphic change during production, distribution, and storage, formulation with the most stable form in the marketed product is considered. In addition, by monitoring each phase of raw material processing, polymorphisms can be controlled during dosage form manufacturing. The objective of this review is to provide concise information on drug polymorphism, their characterization process, their effect on the stability of dosage forms, factors controlling polymorphism in the crystallization process, some case studies on polymorphs, control of polymorphism during the formulation of successful dosage forms and some of the regulatory considerations regarding polymorphs. Various databases like Pubmed/Medline, Google Scholar and Web of Science of all English language articles were searched, and relevant information was collected regarding the importance of polymorphism in formulation development. From a vast literature survey, it was found that polymorphism is a very important tool in a pre-formulation study that provides information about the fate of a drug molecule in its journey. From the present study, it was concluded that the polymorphism property of a drug should be taken into consideration at the pre-formulation stage since it is a very important tool for the formulation of a successful dosage form with stability and efficacy.