Crystal Polymorphism Research Articles

A phase variety of fluorinated ionic liquids: Molecular conformational and crystal polymorph

Crystal polymorphs of fluorinated ionic liquids (fILs) were examined at low-temperature (LT) by Raman spectroscopy. The fILs were 1-alkyl-3-methylimidazolium perfluorobutanesulfonate, [Cnmim][PFBS] (n = 4, 6, and 8). The cations and anion possess conformational degrees of freedom. Various LT phases were derived from the conformational polymorphs of the cations and the anion. Conformational flexibility depended on alkyl chain length. The crystal polymorphs in the fILs were sensitive to molecular conformations and flexibility.

Polymorphism and grating assembly with unique iridescence features in periodically banded poly(ethylene adipate)

Poly(ethylene adipate) (PEA) forms either ring-banded spherulites (RBS) crystallized between T c = 20–32 °C, or ringless spherulites (RLS) if crystallized away from this range. Morphologies differ correspondingly in their interior structures, as well as polymorphism in that α-form crystal is packed in RLS but combination of α, β crystals are dominantly in ring-banded one. Internal structure of banded spherulites is determined by dissection analyses. Interior lamellae of the banded PEA spherulites are assembled as discontinuous concentric-shell structures with concave shapes like cut onions. The radial-direction plate-like lamellae intersection constitutes each shell with the tangential cilia-like lamellae. Interior tangential lamellae bend or branch out perpendicularly at 90° angle in the radial direction to merge with the radial plate-like lamellae. Through designing optimal regularly-banded morphologies, prominent photonic iridescence is attained in the PEA banded spherulites. Moreover, the PEA banded spherulitic morphology can structured the light with circular pattern by laser interference. Light-interfering grating structures for iridescence applications can be achieved by custom-designing the PEA-RBS assemblies. The interior 3D self-assembly in periodically banded poly(ethylene adipate) is analyzed, and proved to be able to custom-structured as gratings, which, along with the top-surface periodicity, are capable of displaying optical iridescence for potential applications. • PEA spherulite morphology differs correspondingly with variation in polymorphism. • Monomorphic crystal is packed in ringless PEA spherulite but polymorphic crystals are dominantly in ring-banded one. • Interior lamellae of the banded PEA spherulites are assembled as discontinuous cross-hatch gratings. • Light-interference grating structures for iridescence applications can be achieved by custom-designing the PEA-RBS.

Application of functionalized magnetic silica nanoparticles for selective induction of three coumarin metastable polymorphs

The precise control of active pharmaceutical ingredient (API) crystal nucleation and polymorphism is a key consideration in pharmaceutical manufacturing. In this study, tunable nanoparticles were developed to regulate the nucleation process of coumarin. Magnetic silica nanoparticles with four different functional groups (–NH 2 , –COOH, –SH, –NCO) were prepared and coated on the substrate for inducing the crystallization of coumarin. Confined melt crystallization and microspacing sublimation crystallization methods were used to investigate the regulation mechanism. The results indicated that three metastable forms of coumarin can be obtained as pure components based on the combined influence of crystallization methods and functionalized nanoparticles. Form II could be selectively obtained by microspacing sublimation crystallization on Fe 3 O 4 @SiO 2 –SH substrates, and Form IV could be obtained by confined melt crystallization on Fe 3 O 4 @SiO 2 –NCO substrates. Form III could be obtained by further heating Form IV crystals to 52 °C on Fe 3 O 4 @SiO 2 –NCO substrates. Moreover, the polarized light microscopy results also indicated that the introduction of nanoparticles could also increase the stability of the metastable crystalline forms of coumarin. Finally, the diffusion and surface dynamics during nanoparticle induced crystallization were comparatively investigated and the corresponding polymorphic selectivity mechanism was proposed.

Polymorphs with Remarkably Distinct Physical and/or Chemical Properties.

Polymorphism in crystals is known since 1822 and the credit goes to Mitscherlich who realized the existence of different crystal structures of the same compound while working with some arsenate and phosphate salts. Later on, this phenomenon was observed also in organic crystals. With the advent of different technologies, especially the easy availability of single crystal XRD instruments, polymorphism in crystals has become a common phenomenon. Almost 37 % of compounds (single component) are polymorphic to date. As the energies of the different polymorphic forms are very close to each other, small changes in crystallization conditions might lead to different polymorphic structures. As a result, sometimes it is difficult to control polymorphism. For this reason, it is considered to be a nuisance to crystal engineering. It has been realized that the property of a material depends not only on the molecular structure but also on its crystal structure. Therefore, it is not only of interest to academia but also has widespread applications in the materials science as well as pharmaceutical industries. In this review, we have discussed polymorphism which causes significant changes in materials properties in different fields of solid-state science, such as electrical, magnetic, SHG, thermal expansion, mechanical, luminescence, color, and pharmaceutical. Therefore, this review will interest researchers from supramolecular chemistry, materials science as well as medicinal chemistry.

New opportunities for sustainable bioplastic development: Tailorable polymorphic and three-phase crystallization of stereocomplex polylactide by layered double hydroxide

Stereocomplexation between enantiomeric poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) is a promising sustainable approach and gaining momentum to overcome the shortcomings of polylactide (PLA) for its use as a replacement for fossil-based plastics. Filler addition in tailoring the crystallization of stereocomplex PLA (SC-PLA) has attracted extensive attention; however, research has primarily focused on the heterogeneous nucleation effect of filler. The impact of filler on the chain behavior of SC-PLA during crystallization has not been exclusively discussed, and the rigid amorphous fraction (RAF) development remains unknown. In this study, the crystallization of PLLA/PDLA blends was modified by low loading of layered double hydroxide (LDH) (≤ 1 wt%) with the proposed local effect of such filler, and additional RAF development was incurred. In the early stage of crystallization, LDH facilitates the pairing of PLLA and PDLA and arrests the ordered SC pairs during the dynamic balance between the separation and pairing of racemic segments. This explains the severely suppressed homochiral (HC) crystallization, promoted SC crystallization, and additional RAF formation driven by the nucleation-induced chain ordering. This work, for the first time, highlights the role of LDH in creating SC-PLA with tailorable polymorphism and RAF, where the mechanism can be extended to other filler-type nucleator systems.

Targeted Crystallization of Rare Earth Carbonate Polymorphs at Hydrothermal Conditions via Mineral Replacement Reactions.

The interaction between rare earth element (REE)-rich (La, Pr, Nd, Dy) aqueous solutions, dolomite (CaMg(CO3)2), and aragonite (CaCO3) at low temperature hydrothermal conditions (25-220°C) is studied. The experiments result in the solvent-mediated surface precipitation and subsequent pseudomorphic mineral replacement of the dolomite and aragonite seeds by newly formed REE-carbonates. The host grains are replaced from periphery inward. The newly formed REE-bearing carbonates in La-, Pr-, and Nd-doped systems follow the crystallization sequence: lanthanite [REE2(CO3)3·8H2O] → kozoite [orthorhombic REECO3(OH)] → hydroxylbastnasite [hexagonal REECO3(OH)]. The interaction of Dy-bearing solutions with dolomite results only in the crystallization of kozoite [orthorhombic DyCO3(OH)]. However, experiments with aragonite reveal a two-step crystallization pathway: tengerite [Dy2(CO3)3·2-3(H2O)] → kozoite [orthorhombic DyCO3(OH)]. The temperature, the dissolution rate of the host mineral, and the ionic radii of the REE3+ in question are found to control the kinetics of the replacement reaction, the polymorph selection, and the crystallization pathways toward bastnasite. The findings allow to gain a more in-depth understanding of the formation REE-bearing carbonates, particularly the mineral bastnasite, which is the main source of REEs for industry. This knowledge can be used to improve REE separation, exploration, exploitation methods, as well to produce carbonate minerals with tailored structures.

Deconstructing extra virgin olive oil through fractionation processes

Arbequina monovarietal extra virgin olive oil (EVOO) was fractionated through a multi-step dry fractionation method. Three of the isolated fractions were selected and analyzed: one being liquid at 4 °C, and two being solid at 4 °C, and at 12 °C. Differential scanning calorimetry (DSC) combined with synchrotron radiation X-ray diffraction (SR-XRD) techniques were employed to monitor the polymorphic crystallization and transformation processes when samples were cooled from the melt to complete crystallization and reheated at a rate of 2 °C/min. Fatty acid profiles and α-tocopherol contents were also determined for EVOO and associated fractions. Each sample exhibited a different and unique crystallization and polymorphic behavior, and the number of crystallizing forms and complexity of transitions increased for solid fractions. In more detail, just two polymorphs (β’3-2L and β’2-2L) were detected in the liquid fraction, whereas the fraction which remained in the solid state at 12 °C exhibited six different phases (α-2L; β’3-2L; β’2-2L; β’1-2L; β’2-3L; β’1-3L). These dissimilarities were strongly correlated with meaningful variations in the fatty acid moieties forming TAG structures and caused large deviations in the crystallization and melting temperatures. As an example, melting temperatures of the liquid and the solid fraction at 12 °C were about −3 °C and 17 °C, respectively. It may be worth exploring the potential of EVOO fractions to be used for improving properties of food stuff, among others. The liquid fraction may be of interest due to its high nutritional value owing to elevated contents in monounsaturated fats and antioxidants, whereas the solid fraction at 12 °C may become a good choice to be used as a high-oleic soft fat.

Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy.

Autofluorescence-detected photothermal mid-infrared (AF-PTIR) microscopy was shown to enable parts-per-million detection of α-indomethacin impurity in γ-indomethacin samples. Subtle differences in the photothermal response of the UV-autofluorescence of two indomethacin crystal polymorphs were used for sub-micron chemical discrimination based on fingerprint region mid-IR spectroscopy. The AF-PTIR assignment was independently confirmed by second harmonic generation (SHG) microscopy, which was shown to reduce the total analysis time by rapidly identifying the suitable fields of view. AF-PTIR microscopy has the potential to assist in the early identification of crystal form impurities in the solid dosage forms development pipeline.

Controlling Characteristics of Glycine Crystals by Reactalyzer

Continuous crystallization is the next step of manufacturing especially at the production of pharmaceutical ingredients. We have developed small-scale continuous taylor-vortex crystallizer that is suitable for research in laboratory. But there was a problem that rotating inner cylinder at high-speed range causes much frictional heat and it raises the temperature of the solution, that may spoil the effort of controlling characteristics of crystals. So, we have developed new taylor-vortex crystallizer that has inner cooling system. We conducted several examinations of anti-solvent crystallization of glycine, which aims to obtain unstable crystal polymorph of glycine continuously. The new crystallizer showed the advantage of crystallizing unstable crystal polymorph.

Ordered Submicrometer Structures Developed by Directional Evaporative Crystallization of Acetaminophen in the Presence of Polymers

Crystallization engineering is crucial for the preparation of drug delivery systems with precise release behavior and improved stability. Although evaporation has been commonly used to prepare pharmaceutical film formulations, controlled evaporative crystallization to achieve uniform crystal size and shape has rarely been investigated. In this study, ordered submicrometer composite structures of acetaminophen (ACM) and polymers were prepared via directional evaporative crystallization controlled by a temperature gradient. The ACM crystals had submicrometer sizes while retaining the original crystal polymorph and were aligned along the direction of the temperature gradient, resulting in line structures having branches with uniform and oriented crystal structures. Although the use of a polymer did not affect conventional oven-crystallized films, it significantly decreased the melting point and heat of fusion of directionally crystallized films. The formation of ordered submicrometer composite structures must rely more on kinetic parameters than thermodynamic parameters since no significant intrinsic molecular interactions were discovered. A wide range of sustained-release characteristics could be obtained depending on the polymer types. This unique fast directional crystallization method could offer a new opportunity for future film delivery systems.

Crystal polymorphism in 2,2'-bipyrimidine-based iridium(III) complexes

Mononuclear iridium(III) complexes, NBu4[IrBr4(bpym)] (1) and [IrBr3(bpym)(MeCN)] (2a and 2b) [NBu4 + = tetra(n-butyl)ammonium cation; bpym = 2,2'-bipyrimidine], have been prepared and characterized. Their crystal structures were determined by single-crystal X-ray diffraction. 1 and 2a crystallize in the monoclinic crystal system with space groups P21/c and P21/n, respectively. The 2b phase crystallizes in the orthorhombic crystal system with space group P212121. In these complexes, each iridium(III) is six-coordinate and bonded to two (1) or three (2a and 2b) nitrogen atoms from bpym and MeCN (2a and 2b) molecules and three (2a and 2b) or four (1) bromides. In all the cases, they exhibit a distorted octahedral environment. 2a and 2b display a packing polymorphism containing π···Br, C–H···Br and Br···Br intermolecular interactions. Further analyses of their crystal structures were performed through the SHAPE and CrystalExplorer programs. The electrochemical properties of 1 and 2 were investigated through cyclic voltammetry (CV) technique, with 1 showing a reversible iridium(III)–iridium(IV) redox process.

Implications of particle size on the respective solid-state properties of naltrexone in PLGA microparticles

A thorough understanding of the complexities in formulating and manufacturing polymeric microspheres is required for new and generic drug applications. Specifically, for an ANDA application for polymeric microsphere-based products, the applicant must meet Q1 (qualitative) and Q2 (quantitative) sameness, and in some cases, Q3 (e.g., microstructural) sameness. Herein, we report the naltrexone crystallinity in a PLGA microparticle system prepared from a dichloromethane-benzyl alcohol solvent system results in a crystallinity dependence as a function of microparticle size from the same batch – illustrating intrabatch microstructural variability. As the particle size increases, the crystallinity increases, with additional polymorphic forms more readily noted at the large particle sizes. Furthermore, during dissolution, a polymorphic transition and/or crystallization occurs at larger size fractions. This study highlights the importance of controlling the manufacturing parameters during microparticle formation, specifically solvent extraction and particle size control. Furthermore, with the approval of generic microparticles formulations on the horizon, this study highlights the importance of Q3, the same components in the same concentration with the same arrangement of matter, whereby microparticles can have varying microstructural properties across particle sizes from the same batch.

A New Approach to Polymorphism in Molecular Crystals: Substrate‐Mediated Structures Revealed by Lattice Phonon Dynamics

AbstractThe issue of polymorphism in molecular crystals is discussed, taking into account the substrate‐mediated structures, that is, structures grown at the interface of different substrates. Bulk and thin films of a compound both share the potentiality to display different crystal forms. However, unlike bulk polymorphs, whose structures are determined by their different molecular packing, thin film structures depend very much on the molecular organization of the organic layers on the substrate, which may, or may not, lead to an ordered structure, depending on the nature of the interface and on the growth conditions. Based on large part in some of the authors’ recent works, these thin film structures are classified as distorted bulk, substrate‐selected and substrate‐stabilized polymorphs, with some subtle differences which may yield a polymorph to belong not exclusively to a single one of these categories. Some experiments are then focused upon, involving charge transport at the interface, as well as how far the effect of the surface goes. Furthermore, the authors comment on how the surface‐mediated structures evolve to the single crystal phase in the cases of pentacene and α‐sexithiophene. Finally, the transition from a 3‐ to a 2D regime of growth is shortly discussed in terms of low‐dimensional disorder.

PLLA crystallization kinetics in dependence of molecular weight

Abstract The effect of molecular weight Mwon the polymorphous crystallization and melting behavior of poly(Llactide) PLLA (L206, L210 and L214) were systemically studied by differential scanning calorimetry (DSC). Melting and reorganization of conformationally disordered crystals (α′-phase) of PLLA are analyzed with respect to the cooling rate qcin a range between about 4 and 50 K/min and the heating rate qhin a range between about 5 and 200 K/min. It was shown that the α′- to α-crystalline phase transition prior to the dominant melting depends on cooling rate qcand Mw. Unlike very high-MwPLLA L214, for low-MwPLLA L206 crystallized at high qc, the α′-form crystals only partially transformed into the α-modification, and certain amounts of α′-form crystals melted directly without α′- to α-transition during the heating process. With increasing qc, the melting of PLLA L210 changed from phase-transition- and -melting mechanism to the common melt-recrystallization mechanism. It was also found that the polymorphism of PLLA significantly affected the crystallization kinetics. Consequently, the reorganization of α′-crystals into stable α- crystals could be inhibited by fast heating (qh> 150 K/min).

The interfacial digestion behavior of crystalline oil-in-water emulsions stabilized by sodium caseinate during in vitro gastrointestinal digestion

The interfacial digestion behavior of crystalline oil-in-water (O/W) emulsions was studied using sodium caseinate-stabilized 4% and 20% palm stearin-in-water emulsions (4% PS and 20% PS) with 4% and 20% palm olein-in-water emulsions as control. Variations in fat crystal form and microstructure, interfacial adsorbed protein percentage and concentration, and rheological properties during in vitro gastrointestinal digestion and intestinal lipid digestion behavior were determined. Initially, fat crystals in both PS-based emulsions were dominated by β′ polymorph. After gastric digestion, the β′-to-β transition was observed and both PS-based emulsions mainly contained β crystals, but 20% PS had a higher β crystal content (∼85% vs. 60%, p < 0.001) and viscosity than 4% PS. These β crystals induced in the gastric phase with large size, dense packing, and a high onset melting temperature (46.8 ± 0.2 °C) probably played a major role in slowing down lipid digestion, as confirmed by a greater extent of decreased lipolysis rate of 20% PS (∼37%) than 4% PS (∼10%) at the initial stage of intestinal digestion. The lipolysis extent of PS-based emulsions is strongly dependent on their solid fat content (SFC). The digestion extent of 4% PS was not affected by its low SFC (2.6%), while a high SFC of 20% PS (12.5%) promoted its lipolysis as fat crystals in it adsorbed at the oil-water interface to facilitate the formation of stable spherical droplets. This study highlighted the crucial role of gastric rather than initial fat crystal polymorph in impacting lipid digestion rate of protein-stabilized O/W emulsions.

Kinetic Phase Diagram for Nucleation and Growth of Competing Crystal Polymorphs in Charged Colloids.

We determine the kinetic phase diagram for nucleation and growth of crystal phases in a suspension of charged colloids. Exploiting the seeding approach in extensive simulations, we calculate nucleation barrier heights for face-centered cubic (fcc) and body-centered cubic (bcc) phases for varying screening lengths and supersaturations. We determine for the entire metastable fluid region the crystal polymorph with the lowest nucleation barrier, and find a regime close to the triple point where metastable bcc can form due to a lower nucleation barrier, even though fcc is the stable phase. For higher supersaturation, we find that the difference in barrier heights decreases and we observe a mix of hexagonal close-packed, fcc, and bcc structures in the growth of crystalline seeds as well as in spontaneously formed crystals. Our kinetic phase diagram rationalizes the different crystallization mechanisms observed in previous work.

Designing Heat-Set Gels for Crystallizing APIs at Different Temperatures: A Crystal Engineering Approach

An organic salt crystallizes through different kinds of charge-assisted hydrogen-bonded networks depending on carboxylic functionality number and the degree of amine. These H-bonded packing patterns are often robust and predictable, so one can design a supramolecular salt with a certain purpose. In some cases, two different crystalline packing patterns can be found in Primary Ammonium Dicarboxylate (PAD) salts at different temperatures. Two kinds of supramolecular bonding, namely, charge-assisted hydrogen bonding and weak van der Waals interactions stabilize the two states. A small increase in the carbon chain length in a primary amine enhances the additional van der Waals interactions with the packing so that the 2D hydrogen-bonded network (HBN) transforms into a 1D HBN at room temperature. Such van der Waals interactions can be controlled by external heat, so a temperature-dependent 1D to 2D phase change is feasible. When certain moieties, such as azo and bipyridine, are introduced into the carboxylic acid backbone, the acids become insoluble in most organic solvents, raising their melting point, and resulting in heat-set gels. In the presence of an API, temperature and solvent-dependent polymorphic crystals can be grown in the heat-set gel medium and by simply cooling down the mixture, the API crystals can be separated easily.

The role of crystal packing on the optical response of trialkyltetrelethynyl acenes.

The electronic and optical responses of an organic semiconductor (OSC) are dictated by the chemistries of the molecular or polymer building blocks and how these chromophores pack in the solid state. Understanding the physicochemical nature of these responses is not only critical for determining the OSC performance for a particular application, but the UV/visible optical response may also be of potential use to determine aspects of the molecular-scale solid-state packing for crystal polymorphs or thin-film morphologies that are difficult to determine otherwise. To probe these relationships, we report the quantum-chemical investigation of a series of trialkyltetrelethynyl acenes (tetrel = silicon or germanium) that adopt the brickwork, slip-stack, or herringbone (HB) packing configurations; the π-conjugated backbones considered here are pentacene and anthradithiophene. For comparison, HB-packed (unsubstituted) pentacene is also included. Density functional theory and G0W0 (single-shot Green's function G and/or screened Coulomb function W) electronic band structures, G0W0-Bethe-Salpeter equation-derived optical spectra, polarized ϵ2 spectra, and distributions of both singlet and triplet exciton wave functions are reported. Configurational disorder is also considered. Furthermore, we evaluate the probability of singlet fission in these materials through energy conservation relationships.

Protective effect of surfactant modified phytosterol oleogels on loaded curcumin.

Oleogels represent one of the most important carriers for the delivery of lipophilic nutraceuticals. Phytosterols (PS), plant-derived natural sterol compounds, are preferred for oleogel preparation due to their self-assembly properties and health function. However, the relationship between the physical properties of PS-based oleogels and the chemical stability of loaded bioactive compounds is still unclear. The influence of lecithin (LC) and glycerol monostearate (GMS) on the physical properties of PS-based oleogels made of liquid coconut oil and the stability of curcumin as a model bioactive loaded in the oleogels was investigated. Results showed that the flow consistency index was much higher for GMS-containing oleogels than that for LC-containing oleogels. The optical microscopy and X-ray scattering analysis showed that the addition of GMS in the PS oleogels promoted the formation of a crystal mixture with different crystal polymorph structures, whereas LC addition promoted the formation of needle-like crystals of PS. Using curcumin as a model lipophilic nutraceutical, the GMS-enriched PS oleogels with high crystallinity and flow consistency index exhibited a good retention ratio and scavenging activity of the loaded curcumin when stored at room temperature. This study shows that enhancing the firmness of oleogels made from PS and liquid coconut oil is beneficial to the retention and chemical stability of a loaded bioactive (curcumin). The findings of the study will boost the development of PS-based oleogel formulations for lipophilic nutraceutical delivery. © 2022 Society of Chemical Industry.

Influence of physical aging of ferroelectric vinylidene fluoride copolymer films on their structural and electrophysical characteristics

AbstractGeneral problems of structural changes which occur at storage of two‐phase crystalline polymers with a metastable structure at room conditions are considered on the example of a vinylidene fluoride ‐ hexafluoropropylene copolymer. The physical aging occurs in flexible‐chain crystalline polymers (polyethylene, fluoropolymers under consideration, etc.), where, due to low glass transition temperatures, the liquid‐like dynamics of amorphous phase chains is realized at room temperature through cooperative micro‐Brownian motions with short relaxation times. Taking into account that covalent‐bound sections of the chains of the amorphous phase can enter the crystallites, the noted mobility may initiate changes in the size of the latter. Such a possibility is proved by the example of the noted copolymer. At low‐temperature crystallization of a vinylidene fluoride ‐ hexafluoropropylene copolymer from a solution the formed α‐phase crystals have little perfection. The size of the crystals increases when the films are stored in room conditions. Because of the crystal polymorphism, at the same time a certain fraction of γ‐phase crystals which are present in initial films undergo a polymorphic transformation γ → α. These processes lead to an increase in crystallinity. Moreover, during such processes additional structuring is observed, which is reduced to the displacement of various kinds of intra‐chain defects into the amorphous phase (and especially into the surface). Since the copolymers under study are ferroelectrics, they were studied by piezo force microscopy. It was found that despite the crystallization predominantly in nonpolar α‐phase, piezo force microscopy revealed a domain structure, which formation mechanism is discussed. The structural changes at physical aging of the films affect the character of the noted domain structure. Thus, it is suggested that the mechanism of the described structural changes is realized through the developed cooperative mobility of the chains in the amorphous phase, which characterizes the processes of rotational diffusion.