Crystal Polymorphism Research Articles

Photophysical properties and stimuli-responsive crystal-state luminescence switching of morpholine-modified naphthalic anhydride derivative

Stimuli-response organic solid-state luminescence switching materials are attracting increasing interest due to their smart photophysical properties. In this study, a morpholine-modified naphthalic anhydride derivative, 4-(4-morpholinyl)naphthalic anhydride (MBC), was synthesized and studied. Its two crystal polymorphs, MBC-G and MBC-O, were obtained under different crystallization conditions. These two distinct crystals show significantly different solid-state luminescence behaviors: a green emission at 535 nm for MBC-G, and an orange emission at 572 nm for MBC-O. Upon fiercely grinding the MBC-G crystal or melting and then quickly cooling it, a phase transition occurs from MBC-G to MBC-O, accompanied by a fluorescence change from green to orange. The reverse transformation from MBC-O to MBC-G can be achieved by recrystallization. The X-ray single crystal structures show that the green emission should be attributed to molecular J-aggregation in the crystal packing, and the orange emission may originate from molecular H-aggregation. This switchable color nature gives MBC the promising candidate for potential smart anti-counterfeiting and light-emitting materials.

Particle design of the metastable form of clopidogrel hydrogen sulfate by building spherulitic growth operating spaces in binary solvent systems

Clopidogrel hydrogen sulfate occupies a large market share of antithrombotic drugs. Its metastable form I has the advantages of high solubility and bioavailability. However, the poor powder properties and stability limit its application. This work solved the issue by building spherulitic growth operating space in “isopropyl acetate + lower alcohol” binary solvent systems. The systems were selected by the indicators of solubility and isosteric adsorption heats. By investigating crystal morphologies, polymorph transformation, and gelation with supersaturation gradient experiment, ATR-FTIR spectroscopy, and inverted tube method, these binary solvent systems follow the supersaturation-dependent spherulitic growth mechanism providing operating spaces significantly larger than the reported single solvent system. Hence, an optimal crystallization process was designed to prepare high-quality spherulites of form I avoiding polymorph transformation and gelation. Compared with the reported single solvent system, the optimized product presents better powder properties with residual solvent decreased by 59% and operating time decreased by 75%–90%.

Novel Physics-Based Ensemble Modeling Approach That Utilizes 3D Molecular Conformation and Packing to Access Aqueous Thermodynamic Solubility: A Case Study of Orally Available Bromodomain and Extraterminal Domain Inhibitor Lead Optimization Series

Drug design with patient centricity for ease of administration and pill burden requires robust understanding of the impact of chemical modifications on relevant physicochemical properties early in lead optimization. To this end, we have developed a physics-based ensemble approach to predict aqueous thermodynamic crystalline solubility, with a 2D chemical structure as the input. Predictions for the bromodomain and extraterminal domain (BET) inhibitor series show very close match (0.5 log unit) with measured thermodynamic solubility for cases with low crystal anisotropy and good match (1 log unit) for high anisotropy structures. The importance of thermodynamic solubility is clearly demonstrated by up to a 4 log unit drop in solubility compared to kinetic (amorphous) solubility in some cases and implications thereof, for instance on human dose. We have also demonstrated that incorporating predicted crystal structures in thermodynamic solubility prediction is necessary to differentiate (up to 4 log unit) between solubility of molecules within the series. Finally, our physics-based ensemble approach provides valuable structural insights into the origins of 3-D conformational landscapes, crystal polymorphism, and anisotropy that can be leveraged for both drug design and development.

Oxidant‐Accelerated Polydopamine Modification Process for the Fast Fabrication of PDA on HMX with Improved Mechanical Stability

AbstractPolydopamine surface coating shows the capability to improve the adhesive properties as well as mechanical stabilities of energetic materials, which is highly desired for the development of insensitive munitions. However, the slow polymerization process of dopamine makes the coating process time‐consuming and uneconomic. Herein, an oxidant‐accelerated strategy was demonstrated to obtain fast polymerization kinetics of dopamine for the surface modification of HMX crystals. Upon the addition of oxidant, PDA was able to form surface layer of HMX particles within 5 min without changing the shape and polymorph of HMX crystals. The PDA coating showed the ability to improve the wettability of HMX, contributing to its abundant active groups. Moreover, the mechanical stability of PDA on HMX (HMX@PDA) samples was improved accompany with the increasing coating time, and the friction explosion probability and drop height of 300 s treated sample were 40 % and 64 cm, respectively. The detonation velocity was also measured, which showed that the effect of PDA coating on the detonation velocity of HMX was not significant. More importantly, our protocol showed the capability to fabricate HMX@PDA with different particle sizes on a large scale, satisfying the application demands of insensitive high explosives.

Characterisation of Fat Crystal Polymorphism in Cocoa Butter by Time-Domain NMR and DSC Deconvolution.

The polymorphic state of edible fats is an important quality parameter in fat research as well as in industrial applications. Nowadays, X-ray diffraction (XRD) is the most commonly used method to determine the polymorphic state. However, quantification of the different polymorphic forms present in a sample is not straightforward. Differential Scanning Calorimetry (DSC) is another method which provides information about fat crystallization processes: the different peaks in the DSC spectrum can be coupled to the melting/crystallisation of certain polymorphs. During the last decade, nuclear magnetic resonance (NMR) has been proposed as a method to determine, qualitatively and/or quantitatively, the polymorphic forms present in fat samples. In this work, DSC- and NMR-deconvolution methods were evaluated on their ability to determine the polymorphic state of cocoa butter, with XRD as a reference method. Cocoa butter was subjected to two different temperature profiles, which enforced cocoa butter crystallization in different polymorphic forms. It was found that XRD remains the best method to qualitatively determine the polymorphic state of the fat. Whereas the quantitative NMR and DSC deconvolution results were not fully in line with the XRD results in all cases, NMR deconvolution showed great promise both in a qualitative and quantitative way.

Anomalous structure transition in undercooled melt regulates polymorphic selection in barium titanate crystallization

The crystallization processes of titanates are central to the fabrication of optical and electrical crystals and glasses, but their rich polymorphism is not fully understood. Here, we show when and how polymorphic selection occurs during the crystallization of barium titanate (BaTiO3, BT) using in situ high energy synchrotron X-ray diffraction and ab initio molecular dynamic simulation. An anomalous structure transition is found in molten BT during cooling across the cubic-hexagonal transition temperature, which enables nucleation selection of BT by manipulating the undercooling: a cubic phase is preferred if nucleation is triggered at large undercooling, whereas a hexagonal phase is promoted at small undercooling. We further reveal that the nucleation selection between the cubic and the hexagonal phase is regulated by the intrinsic structure property of the melt, in particular, the degree of polymerization between Ti-O polyhedra. These findings provide an innovative perspective to link the polymorphic crystallization to the non-isomorphic structure transition of the melt beyond the conventional cognition of structural heredity.

Thermodynamic characteristics of L-histidine polymorphs and effect of ethanol on the crystallization

L-Histidine(L-His) has two polymorphs of FormA and FormB. It is known that the crystallization of polymorphs is influenced by antisolvents. In this study, crystal morphology of polymorph was considered from prediction of crystal structures. Next, the effects of ethanol on polymorphs and morphology of L-His were studied by evaluating crystals obtained from saturated aqueous solutions by cooling or adding of ethanol. From the prediction of crystal structures, It is suggested that FormA crystal tend to grow in the long side direction. Experiments show that FormA tends to be obtained from aqueous solvent, on the other hands, FormB tends to be obtained from ethanol existing solution. However, FormB were found to dissolve gradually and transited to FormA. Furthermore, results show high concentration of ethanol change the morphology along its thickness direction, so it suggests that the effect of antisolvents has a big influence on crystallization. Moreover, the results of Thermogravimeter-Differential Thermal Analyzer (TG-DTA) and Differential Scanning Calorimetry (DSC) analysis demonstrate that FormB, which is thought as a metastable form, is possibly favorable in term of thermal stability and suggests the behavior of melting and decomposition of L-His.

Coupling effect of pressure and flow fields on the crystallization of Poly(vinylidene fluoride)/Poly(methyl methacrylate) miscible blends

During polymer processing, the polymeric blends are inevitably subjected to coupled external fields (flow, pressure, and temperature), which have great effects on the phase behavior, crystallization behavior, crystalline structure, and final properties of blends. A typical crystalline/amorphous miscible blend system, poly(vinylidene fluoride)/Poly(methyl methacrylate) (PVDF/PMMA) blend, is chosen to understand the coupling effect of processing fields on crystallization behavior of the blends. It is found that shear flow can induce locally oriented trans conformation, which finally transforms into polar β/γ phases during isothermal crystallization under pressure. Interestingly, under pressure, β and γ phases exhibit different sensitivities to shear rate. The γ phase is easily formed at low shear rate, while higher shear rate is required to induce β phase formation, which could be related to the sequence length of the oriented trans conformation induced by shear flow. As for the addition of PMMA, the hydrogen bonding interactions between carbonyl groups of PMMA and hydrogen atom of PVDF could stabilize the shear-induced local trans conformation and subsequently lead to more β/γ phases. Meanwhile, different from PVDF crystallized under static condition, the shear flow and PMMA synergistically induce the transformation from spherulitic to shish-kebab-like structure and highly oriented thick β phase with higher melting point. To the best of our knowledge, it is the first time to reveal the unique crystallization behaviors of PVDF/PMMA blends induced by flow field coupled with pressure. This work could provide a significant guidance for the control of crystal polymorphs of PVDF/PMMA miscible blends during processing.

Nitro–Nitrito Photoisomerization of Cationic Platinum(II) Complexes in the Solid State: Reactivity in Polymorphic Crystals and Glassy State

Nitro–nitrito isomerization is a well-known photoreaction exhibited by metal complexes in the solid state. We previously reported that the isomerization ratio in the salts of a cationic platinum(II...

Ameliorative Effect of Multi Herbal Formulation on Lipid Peroxidation and Redox Dysfunction in Ethanol Induced Hepatic Imbalance

Abstract: Introduction: Urolithiasis has afflicted human race since the days of yore. Conventional treatment acts only on associated ailments whereas pharmacologically active phytoconstituents derived from plants are reported to possess lithotriptic as well as anti-urolithiatic effect, thus herbal sources need to be scientifically explored. Present study was aimed to evaluate anti-urolithiatic potential of leaves of Alstonia scholaris and its isolated pentacyclic triterpenoids: lupeol and ursolic acid in ethylene glycolinduced renal calculi rat model. Materials and Methods: Leaves of Alstonia scholaris were extracted with various solvents, amount of triterpenoids in each extract was quantified using HPTLC. Extract which had higher amount of triterpenoid was evaluated for its anti-urolithiatic effect. Albino wistar rats of either sex were divided into 6 groups. All groups except vehicle were fed with 0.75%v/v of ethylene glycol for 28 days. Treatment with standard cystone, low and high dose of extract and pentacyclic triterpenoids were given to respective groups from 4th-28th day of study. On 28th day, serum creatinine, uric acid, BUN, TNF-α, IL-6 and urinary electrolyte levels were estimated. Kidneys were isolated, one was used for histopathological study and other for antioxidant assays. Results and Discussion: Histopathological examination of kidneys revealed destructed morphology due to deposition of large polymorphic crystals and cystic dilatation of tubules. Whereas treatment with extract and its pentacyclic triterpenoids prevented renal damage and deposition of crystals. Perturbations in levels of nitrogenous wastes, inflammatory mediators and urinary electrolytes were also prevented. Alstonia scholaris rich in triterpenoid significantly arrested associated oxidative stress and inflammation thus preventing formation of renal calculi. Conclusion: Leaves of Alstonia scholaris and pentacyclic triterpenoids isolated from them demonstrates potent herbal remedy for treatment of urolithiasis. Key words: Alstonia scholaris, Anti-inflammatory, Lupeol, Oxidative stress, Ursolic acid, Urolithiasis.

Insights into Excimer Formation Factors from Detailed Structural and Photophysical Studies in the Solid‐State

AbstractSolid‐state luminescent materials are essential for the development of optoelectronic devices like lasers, sensors, and organic light‐emitting diodes. Organic molecules reveal several benefits like stability, costs, and environmental compatibility compared to metal‐based materials. As common organic fluorophores often suffer from aggregation‐caused quenching, different strategies have been established to overcome this quenching, which are mainly based on intramolecular modifications. Controlling the photophysical properties via intermolecular interactions is more challenging and less investigated. The formation of excited dimers (excimers) bears great potential for obtaining efficient solid‐state luminescent materials. As the excimer‐formation process is strongly dependent on the non‐covalent interactions, a full understanding of the structure–property relationship is essential. In this study, structurally simple thiophosphoranyl anthracene excimers and the dependency of the photophysical properties on the solid‐state arrangement are investigated. Through crystallization of polymorphs and co‐crystals, the resulting intermolecular interactions have been modulated over a broad range. Novel insights into the excimer formation factors and the dependence of the photophysical properties on the intermolecular interactions are obtained. This study will help in the development and controlling the photophysical properties of solid‐state luminescent materials.

Understanding the Salt-Dependent Outcome of Glycine Polymorphic Nucleation.

The salt-dependent polymorphs of glycine crystals formed from bulk solutions have been a longstanding riddle. In this study, in order to shed fresh light, we studied the effects of seven common salts on primary nucleation of the metastable α-glycine and the stable γ-glycine. Our nucleation experiments and in-depth data analyses enabled us to reveal that (NH4)2SO4, NaCl and KNO3, in general, promote γ-glycine primary nucleation very significantly while simultaneously inhibiting α-glycine primary nucleation, thereby explaining why these three salts induce γ-glycine readily. In comparison, Ca(NO3)2 and MgSO4 also promote γ-glycine and inhibit α-glycine primary nucleation but not sufficiently to induce γ-glycine. More interestingly, Na2SO4 and K2SO4 promote not only γ-glycine but also α-glycine primary nucleation, which is unexpected and presents a rare case where a single additive promotes the nucleation of both polymorphs. As a result, the promoting effects of Na2SO4 and K2SO4 on γ-glycine do not enable γ-glycine nucleation to be more competitive than α-glycine nucleation, with γ-glycine failing to appear. These observations help us to better understand salt-governed glycine polymorphic selectivity.

Chiral Polymorphic Hydrazine-based Asymmetric Liquid Crystal Trimers with Resorcinol as Linking Group.

This is the first report on chiral polymorphic hydrazine-based asymmetric liquid crystal trimers, 1-[4'-(4''-(5-Cholesteryloxy)carbonyl)butyloxy]-3-[N-benzylideneoxy-N'-(4'''-decyloxybenzylidene) hydrazine] butyloxybenzenes, and 1-[4'-(4''-(10-cholesteryloxy)carbonyl)nonyloxy]-3-[N-benzylideneoxy-N'-(4'''- decyloxybenzylidene)hydrazine]butyloxybenzenes., in which the hydrazine and cholesterol arms were connected via two flexible methylene spacers (n = 3-12 units and m = 4 or 9, respectively) to the central resorcinol core. FT-IR, 1D and 2D NMR spectroscopy, and CHN microanalysis were used to elucidate the structures of the trimers. Differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction were used to study the transitional and phase properties of the trimers, which were length and spacer parity dependent. Trimers with short spacer length in the cholesteryl arm, m = 4 showed an interesting phase sequence of BP/N*-TGBA*-SmA*. The TGBA* phase was sensitive to spacer length as it was only observed in trimers with short ester linkage. For the long analogues, m = 9, characteristic visible reflection and a much simpler phase sequence with only N* and SmA* phases were observed. The X-ray diffraction measurements revealed that layer periodicities of the SmA* phase were approximately half the estimated all-trans molecular length (d/L ≈ 0.44-0.52), thus suggesting that the molecules are either strongly intercalated or bent.

Morphology and composition of Goldeye (Hiodontidae; Hiodon alosoides) otoliths

We provide up-to-date morphological and compositional data on otoliths of the osteoglossomorph Goldeye (Hiodon alosoides). Using computed tomography (CT) X-ray, we documented the location of each of the three pairs of otoliths (lapilli, sagittae, and asterisci) in relation to the swim bladder, which extended forward in close proximity to the sagittae and asterisci. The lappili were the largest otoliths in terms of surface area and volume, but the sagittae were highly modified, appearing spiral in shape when viewed dorsally, with a surface area to volume ratio more than double that of the lapilli. Using scanning electron microscopy, the surface of each otolith was viewable in great detail, and small otoconia (~10.5 μm diameter) were observed on each, but were most numerous on the sagittae. On scanning electron micrographs, the sagittae appeared to be bi-lobed, with asymmetrical lobes each oriented in the same general direction. Using neutron and X-ray diffraction methods, we found three polymorphs of calcium carbonate crystals (aragonite, vaterite, and calcite), sometimes all within the same otolith. However, in general, lapilli and sagittae were composed predominately of aragonite whereas asterisci were composed chiefly of vaterite. With these results, we provide information on a unique species, whose inclusion in future studies would benefit our understanding of fish hearing, fish evolution, and fisheries ecology.

Experimental Constraints on the Crystallization of Silica Phases in Silicic Magmas

Abstract Low-pressure silica polymorphs, e.g. quartz (Qtz), tridymite (Trd), and cristobalite (Crs), are common in silicic magmas, but the conditions of their formation are still unclear. The stability fields of these polymorphs have been determined in the SiO2, SiO2–H2O, and haplogranite systems, but these simple systems are not directly applicable to silica polymorph crystallization in natural silicic magmas. The present study compiles an experimental database of new and previously-published data documenting the crystallization of silica phases in natural silicic magmas and simple synthetic systems. Silica polymorphs are identified using Raman spectroscopy and their pressure-temperature domains of occurrence and chemical compositions are determined at pressures between 0·1 and 200 MPa, temperatures between 685 to 1200° C, and under H2O-saturated and H2O-undersaturated conditions. Qtz is the stable silica polymorph at pressures higher than 25–30 MPa, temperatures between ∼700 and 950° C, and occurs for a narrow range of melt SiO2 contents (∼79–81 wt %). Constraints on Qtz stability derived from simple systems are mutually compatible with, and thus applicable to natural compositions. This is consistent with Qtz compositions being close to ‘pure’ SiO2, both in experiments and nature. In volcanic systems, Qtz crystallization may occur in magmatic reservoirs and deep volcanic conduits. Trd did not crystallize in the experiments conducted as part of this study despite several experiments having been performed in the Trd stability field. This is consistent with results from the literature which show that Trd crystallization is kinetically inhibited in particular relative to Crs. Natural Trd have compositions deviating substantially from ‘pure’ SiO2, so that stability limits determined in simple systems should not be applied directly to natural cases. Crs was encountered at pressures below 20–30 MPa (or H2O contents < ∼1·5 wt %), from sub-solidus (∼800° C) to near-liquidus (up to 1040° C), and coexisting with melts having a large range of SiO2 contents (70–81 wt %). The Crs stability field is much larger in natural magmas compared to pure SiO2 systems. Crs is a metastable phase stabilized by components (Al, Na, K; about 3 wt %) present in the silicic melt. In volcanic systems, Crs crystallization may thus be restricted to subsurface manifestations such as lava domes.

Usage of Quantum Chemical Methods to Understand the Formation of Concomitant Polymorphs of Acetyl 2-(N-(2-Fluorophenyl)imino)coumarin-3-carboxamide.

Crystallization of concomitant polymorphs is a very intriguing process that is difficult to be studied experimentally. A comprehensive study of two polymorphic modifications of acetyl 2-(N-(2-fluorophenyl)imino)coumarin-3-carboxamide using quantum chemical methods has revealed molecular and crystal structure dependence on crystallization conditions. Fast crystallization associated with a kinetically controlled process results in the formation of a columnar structure with a nonequilibrium molecular conformation and more isotropic topology of interaction energies between molecules. Slow crystallization may be considered as a thermodynamically controlled process and leads to the formation of a layered crystal structure with the conformation of the molecule corresponding to local minima and anisotropic topology of interaction energies. Fast crystallization results in the formation of a lot of weak intermolecular interactions, while slow crystallization leads to the formation of small amounts of stronger interactions.

Enzymatic Interesterification of Palm Stearin and Palm Olein Blend Catalyzed by sn-1,3-Specific Lipase: Interesterification Degree, Acyl Migration, and Physical Properties

Acyl migration of fatty acid at sn-2 is often observed alongside enzymatic interesterification (EIE), causing the loss of lipase selectivity toward the acyl group at sn-1,3. In this study, an oil blend consisting of palm stearin (PST) and palm olein (POL) was interesterified via a chemical interesterification (CIE) and enzymatic method using a packed bed reactor. Characterization in terms of the triacylglycerol (TAG) compositions, sn-2 fatty acid distributions, and solid fat content profiles was performed. In comparison to that of CIE fats, EIE fats showed different modification effects on the solid fat content. Under similar reaction conditions, different interesterification degrees (IDs) were obtained according to the various blend ratios. Using the same mass ratio of substrates (POL/PST of 9:1), the EIE reaction time and temperature affected the ID and the change in the fatty acyl group at the sn-2 position. Under the reaction time of 46 min, an ID of 94.41% was acquired, while at 80 °C, the degree of acyl migration at sn-2 was 92.87%. EIE with high acyl migration exhibited a lower crystallization rate than that of EIE with low acyl migration. However, the effect of acyl migration on crystal polymorphism and oxidative stability was insignificant. Outcomes from this study are meaningful for the establishment of a theoretical basis for a controlled positional-specific EIE that is catalyzed by sn-1,3-specific lipase.

Hexamorphism of Dantrolene: Insight into the Crystal Structures, Stability, and Phase Transformations

Dantrolene represents yet another interesting example of abundant molecular crystal polymorphism existing in at least six different neat polymorphs, three of which can be obtained via crystallizati...

Enhanced Nonisothermal Crystallization and Heat Resistance of Poly(l-lactic acid) by d-Sorbitol as a Homogeneous Nucleating Agent

We report on enhancing crystallization and heat resistance of poly(l-lactic acid) (PLLA) by d-sorbitol as a small molecule nucleating agent via melt blending. During the reheating process, the cold crystallization disappeared and the crystallinity of nucleated PLLA exceeded 50%. The heat deflection temperature of PLLA was elevated from 56 to 132 °C by simply increasing the mold temperature (90 °C) without an additional annealing treatment. We also observed the polymorphic crystals of PLLA during melt crystallization, i.e., the coexistence of hexagonal and lenticular crystals, along with their various geometrical aggregates in addition to plenty of conventional spherulites. On the basis of the fact that the nonisothermal crystallization temperature of PLLA (110 °C at a cooling rate of 10 °C/min) was higher than the melting point of d-sorbitol (about 93 °C), we speculated that d-sorbitol promoted the crystallization of PLLA through a homogeneous nucleation mechanism.

Preparation and characterization of oleogels and emulgels with glycerol monooleate–cholesterol mixtures

This study aimed to prepare and characterize oleogels and emulgels with glycerol monooleate (GMO): cholesterol gelator system. Oleogels, including 5 and 10% of each gelator were prepared. Emulgels with the same organogelator mixture concentrations, and 10 and 20% water phase were also prepared successfully. The gelation time decreased as the added gelator mixture and water concentrations increased. All samples had significant oil binding capacity and creamish-white colors. The oleogels melted just below body temperature, while emulgels melted around body temperature as determined by differential scanning calorimetry. The samples’ crystalline networks were observed with the X-ray diffraction analysis and displayed β and β′ polymorphic type crystals. Rheological measurements revealed that as gelator mixture concentration increased, gel strength enhanced, but in the emulgels, the gel strength decreased significantly as added water content increased. All oleogels and emulgels showed time-dependent thixotropic recovery ability. Temperature ramp tests indicated that the oleogels were stable up to 28 °C, but the emulgels kept their gelled consistency up to 70 °C. Overall, the common properties of these new oleogel and emulgels were provided. Future studies for some applications are foreseen.