Crystal Polymorphism Research Articles

Synthesis of Aragonite from Precipitated Calcium Carbonate: A Pilot Scale Study

The CO2 mineralization pathway is considered a promising option for carbon capture usage and storage because the captured CO2 can be permanently stored, and secondly industrial waste (i.e., petrochemical refinery, lime, and cement kiln dust) can be recycled into value-added carbonate materials by controlling the crystal polymorphs and properties of mineral carbonate. This study investigated the CO2 mineralization utilized for the synthesis of precipitated calcium carbonate (PCC) via low temperatures at 30 °C and 55 °C with the addition of 50 and 75 g/L of ammonium chloride (NH4Cl). The pilot scale of PCC production was established to simultaneously produce PCC with low energy demand by reporting the feasibility of economic analysis and to develop the mineral carbonation that can transform limestones and CO2, which was captured from the petrochemical refinery process into economically valuable PCC. It is found that the aragonite phase of PCC can be generated at a room temperature of 30 °C by adjusting the CO2 flow rate. In addition, the use of NH4Cl, which transformed into ammonium carbonate ((NH4)2CO3) during the calcination process, can maintain the stable aragonite phase by varying the NH4Cl concentration.

Crystal Structure of Ritonavir Polymorphs I and II Revisited with the Application of NMR Crystallography.

Ritonavir, a protease inhibitor sold under the brand name Norvir®, is an antiviral medication that effectively targets the human immunodeficiency virus (HIV). Being probably the most important and best-known example of the crystal polymorphism in the field of pharmaceutics, ritonavir has been extensively studied in the last 30 years, which eventually led to the discovery of its new polymorph, Form III, in 2023. So far, two crystal structures of both Forms I and II of ritonavir were deposited in CCDC database. The aim of this study was to revisit those crystal structures, using NMR crystallography by recording the 13C CP/MAS NMR spectra and performing GIPAW NMR calculations with CASTEP. The obtained results revealed the major discrepancies between the calculated and experimental NMR chemical shift values. Those differences were explained at the molecular level, as resulting from the differences in the experimentally determined and DFT-optimized positions of some atoms, mostly those forming phenyl and thiazole rings. This work is an example of how NMR crystallography can be used to verify and improve the already published crystal structures.

Polymorphic crystallization and transformation pathways of 1,2-dipalmitoyl-3-oleoyl-rac-glycerol (PPO) during a liquid–solid-liquid journey

Abstract The polymorphic behavior of triacylglycerol (TAG) crystals formed during the manufacturing process of lipid-based food products relates directly to their textural and melting properties. In this work, we analyzed the polymorphic crystallization and transformation behavior of 1,2-dipalmitoyl-3-oleoyl-rac-glycerol (PPO), a widespread TAG in edible fats and oils, during the application dynamic thermal treatments of cooling and heating. By implementing calorimetric, X-ray diffraction, and microscopy techniques, we mapped the polymorphic occurrence and the polymorphic transformation pathways of PPO as a function of the rate of thermal treatments. The results obtained were later compared to that reported for diverse TAGs in previous studies. Despite the overall crystallization and transformation behavior of PPO following a similar trend to other TAGs close in fatty acid composition, we can highlight the much lower influence of varying cooling and heating conditions on the crystallization properties of this TAG. In more detail, crystalline forms of low stability were generally promoted during crystallization, whereas transformations occurred always through the melt independently of the heating conditions. One may expect this behavior to influence the industrial processing and final properties of food products based on edible fats containing PPO.

Synthesis and Characterization of New Organoammonium, Thiazolium, and Pyridinium Triiodide Salts: Crystal Structures, Polymorphism, and Thermal Stability

Triiodide salts are of interest for a variety of applications, including but not limited to electrochemical and photochemical devices, as antimicrobials and disinfectants, in supramolecular chemistry and crystal engineering, and in ionic liquids and deep eutectic solvents. Our work has focused on the design of salt–solvate cocrystals and deep eutectic solvents in which the triiodide anion interacts as a halogen bond acceptor with organoiodine molecules. To understand structure–property relationships in these hybrid materials, it is essential to have benchmark structural and physical data for the parent triiodide salt component. Herein, we report the structure and thermal properties of eight new triiodide salts, three of which exhibit polymorphism: tetrapentylammonium triiodide (1a and 1b), tetrahexylammonium triiodide (2), trimethylphenylammonium triiodide (3), trimethylbenzylammonium triiodide (4), triethylbenzylammonium triiodide (5), tri-n-butylbenzylammonium triiodide (6), 3-methylbenzothizolium triiodide (7a and 7b), and 2-chloro-1-methylpyridinium triiodide (8a and 8b). The structural features of the triiodide anion, Raman spectroscopic analysis, and melting and thermal decomposition behavior of the salts, as well as a computational analysis of the polymorphs, are discussed. The polymorphic pairs here are distinguished by symmetric versus asymmetric triiodide anions, as well as different packing patterns. Computational analyses revealed more subtle differences in their isosurface plots. Importantly, this study provides reference data for these new triiodide salts for comparison to hybrid cocrystals and deep eutectic solvents formed from their combination with various organoiodines.

Exploring the functional properties and utilisation potential of mollusca shell by-products through an interdisciplinary approach

Molluscan shellfish aquaculture contributes to 42.6% of global aquaculture production. With a continued increase in shellfish production, disposal of shell waste during processing is emerging as an environmental and financial concern. Whilst major commercial species such as Crassostrea spp. has been extensively investigated on usage of its shell, with information that are crucial for valorisation, e.g. safety and crystal polymorphs, evaluated. There is currently little understanding of utilisation opportunities of shell in several uprising Australian commercially harvested species including Akoya Oyster (Pinctada fucata), Roe’s Abalone (Haliotis roei) and Greenlip Abalone (Haliotis levigata), making it challenging to identify ideal usages based on evidence-based information. Therefore, in this study, an interdisciplinary approach was employed to characterise the shells, and thereafter suggest some potential utilisation opportunities. This characterisation included crude mineral content, elemental profiling and food safety evaluation. As well, physical, chemical, and thermal stability of the shell products was assessed. TGA result suggests that all shells investigated have high thermal stability, suggesting the possibility of utilisation as a functional filler in engineering applications. Subsequent FTIR, SEM and XRD analyses identified that CaCO3 was the main compositions with up to 77.6% of it found to be aragonite. The spectacular high aragonite content compared to well-investigated Crassostrea spp. suggested an opportunity for the utilisation of refined abalone shell as a source of biomedical engineering due to its potent biocompatibility. Additionally, safety evaluations on whole shell also outlined that all investigated samples were safe when utilised as a crude calcium supplement for populations > 11 years old, which could be another viable options of utilisation. This article could underpin abalone and akoya industries actions to fully utilise existing waste streams to achieve a more sustainable future.

Virtual Screening, Polymorphism, and Formation Thermodynamics Study of Riluzole Multicomponent Crystals with Dihydroxybenzoic Acids

Virtual Screening, Polymorphism, and Formation Thermodynamics Study of Riluzole Multicomponent Crystals with Dihydroxybenzoic Acids

Plasmonic Observation of High‐Density Nanoclustering in Low‐Temperature H2O

There has been considerable scientific interest in comprehending the behavior and phase transitions of H2O at the nanoscale in low temperatures. Herein, a highly sensitive and nondestructive surface plasmonic detection system operated at low temperatures to investigate the real‐time nanoscale variation in H2O density from a rapidly cooled thin ice layer formed at 77 K is employed. The nanoslit device exhibits a distinct plasmonic response at 180–250 K, correlated to an increase in the local density of H2O at the nanometer scale. Along with theoretical analyses, it is revealed that high‐density H2O clusters form by vigorous aggregation of H2O molecules within the interphase liquid region between polymorphic ice crystals. The utilization of ice‐active materials, known to inhibit ice growth, suppresses the initiation of such high‐density nanoclustering at 180 K. These results contribute to the comprehension of the interplay between polymorphic crystals and density‐variant interphases in low‐temperature H2O systems.

Reprecipitation-mediated regulation on the surface architecture of uniform spray dried lactose microspheres

Lactose microspheres (LMs) are commonly used in the pharmaceutical field. Although the surface architecture of LMs directly correlates with the performance of the final products, surface manipulation remains challenging. In this study, uniform LMs were fabricated using template-assisted spray drying with polyethylene glycol 200 as the template. The influence of the solvent composition (methanol, ethanol, 1-butanol, and acetone, with and without added water) and post-treatment parameters (time and temperature) on the moisture content, particle morphology, surface architecture, and crystal polymorphism were investigated. The sample surfaces post-treated using methanol were covered with particulate crystals with a crystallinity of ∼88.3 %, whereas those treated using acetone were covered by coral-like crystals with a crystallinity of ∼80.6 %. This is attributed to the higher solubility of lactose in methanol than in acetone. Adding a small amount of water to the post-treatment solvent facilitated amorphous lactose reprecipitation, achieving a block-like crystal stacking surface with a more stable Lα∙H2O content (∼40.4 % w/w). Lα∙H2O enriched on the LM surfaces prevents water absorption during storage, thus maintaining their high dispersity, uniformity, and surface architecture. This study provides a promising strategy for tailoring the surface architecture of spherical crystalline lactose microspheres.

Effects of interesterification with solid base catalyst on physicochemical properties of lard and high-oleic sunflower oil blends

Interesterified blends of lard (LA) and high-oleic sunflower oil (HOSO) were prepared by using a self-synthesized solid base catalyst (K2CO3/GCN). The effect of interesterification on the physicochemical properties of blends was investigated by analyzing the triacylglycerol (TAG) composition, slip melting point (SMP), solid fat content (SFC), thermal properties, crystal polymorphism, and micromorphology. The results proved that interesterification significantly modified the physicochemical properties of the blends. The interesterified products had lower SMPs and steeper SFC curves than the individuals. The interesterified product (CIE-5:5) had the widest plastic range (5.7–18.6 °C), and its increase rate of OPO and OPL total content was up to 38%. The differential scanning calorimetry melting and cooling thermograms showed an obvious change after interesterification. These changes were mostly due to the alternations in TAG compositions. The wide-angle X-ray diffraction results indicated that the crystal form of blends transformed from β′ to β-form after interesterification. Because of the transformation of crystal polymorphism, the micromorphology of interesterified blends differed greatly from the physical blends at the same ratio. The changes in crystal morphology are beneficial for the application of LA-HOSO blends. This work provides an alternative option for extending the use of native lard and high-oleic sunflower oil.

Polymorph sampling with coupling to extended variables: enhanced sampling of polymorph energy landscapes and free energy perturbation of polymorph ensembles.

A novel approach to computationally enhance the sampling of molecular crystal structures is proposed and tested. This method is based on the use of extended variables coupled to a Monte Carlo based crystal polymorph generator. Inspired by the established technique of quasi-random sampling of polymorphs using the rigid molecule constraint, this approach represents molecular clusters as extended variables within a thermal reservoir. Polymorph unit-cell variables are generated using pseudo-random sampling. Within this framework, a harmonic coupling between the extended variables and polymorph configurations is established. The extended variables remain fixed during the inner loop dedicated to polymorph sampling, enforcing a stepwise propagation of the extended variables to maintain system exploration. The final processing step results in a polymorph energy landscape, where the raw structures sampled to create the extended variable trajectory are re-optimized without the thermal coupling term. The foundational principles of this approach are described and its effectiveness using both a Metropolis Monte Carlo type algorithm and modifications that incorporate replica exchange is demonstrated. A comparison is provided with pseudo-random sampling of polymorphs for the molecule coumarin. The choice to test a design of this algorithm as relevant for enhanced sampling of crystal structures was due to the obvious relation between molecular structure variables and corresponding crystal polymorphs as representative of the inherent vapor to crystal transitions that exist in nature. Additionally, it is shown that the trajectories of extended variables can be harnessed to extract fluctuation properties that can lead to valuable insights. A novel thermodynamic variable is introduced: the free energy difference between ensembles of Z' = 1 and Z' = 2 crystal polymorphs.

Thermoplastic starch/poly(butylene adipate-co-terephthalate) blown film with maltol and ethyl maltol preserving cake quality: Morphology and antimicrobial function

Maltol (MT) and ethyl maltol (EM) are flavoring compounds that release vapors into headspace, exerting antimicrobial effects and extending food shelf-life. This study investigated biodegradable films for packaged bakery quality. Biodegradable films (40 % polybutylene adipate terephthalate and 60 % thermoplastic starch) were produced via extrusion for films with varying MT and EM contents (1, 3, and 5 %). Scanning electron microscopy revealed smoother and more homogeneous film cross-sections with MT/EM, indicating reduced surface wrinkling. Fourier-transform infrared spectroscopy analysis suggested modified OH and CH stretching due to hydrogen bonding between TPS and EM/MT. The XRD pattern showed sharp MT crystallization, modifying crystal polymorphs of starch and PBAT. EM and MT films exhibited against Staphylococcus aureus after 24 h. Moreover, EM/MT films effectively delayed fungal growth in butter cake, inhibiting mold growth in butter cake more than twofold. These findings suggest that volatile compounds like MT/EM have promising potential for incorporation into PBAT/TPS films, creating active bakery packaging.

Data-efficient fine-tuning of foundational models for first-principles quality sublimation enthalpies.

Calculating sublimation enthalpies of molecular crystal polymorphs is relevant to a wide range of technological applications. However, predicting these quantities at first-principles accuracy - even with the aid of machine learning potentials - is a challenge that requires sub-kJ mol-1 accuracy in the potential energy surface and finite-temperature sampling. We present an accurate and data-efficient protocol for training machine learning interatomic potentials by fine-tuning the foundational MACE-MP-0 model and showcase its capabilities on sublimation enthalpies and physical properties of ice polymorphs. Our approach requires only a few tens of training structures to achieve sub-kJ mol-1 accuracy in the sublimation enthalpies and sub-1% error in densities at finite temperature and pressure. Exploiting this data efficiency, we perform preliminary NPT simulations of hexagonal ice at the random phase approximation level and demonstrate a good agreement with experiments. Our results show promise for finite-temperature modelling of molecular crystals with the accuracy of correlated electronic structure theory methods.

Cold crystallization behavior of poly(lactic acid) induced by poly(ethylene glycol)-grafted graphene oxide: Crystallization kinetics and polymorphism

Cold crystallization between the glass transition and melt temperature is of particular significance for crystalline regulation due to the slow crystallization rate of poly(lactic acid) (PLA). Incorporation of nucleation agents can promote PLA crystallization by reducing the nucleation activation energy and offering nucleation sites. Herein, we investigated the cold crystallization behavior of PLA induced by poly(ethylene glycol)-grafted graphene oxide (PEGgGO) which was synthesized and identified as a powerful nucleation agent for melt crystallization. The obtained results showed that PEGgGO not only accelerated the cold crystallization kinetics of PLA, but also promoted the polymorphic transition kinetics during the heating process. The half crystallization time of PLA induced by PEGgGO was shortened by 51 % and the final crystallinity increased by 57 % compared to that induced by GO alone at the same loading of 0.5 wt%. In addition, relative to GO, PEGgGO enabled the α′-to-α phase transition kinetics of PLA by a reduced transition temperature range of 26 % due to its excellent nucleation ability even at cold crystallization. The flexible PEG chains on GO facilitated crystalline regulation of PLA owing to the improved chain mobility. This work provides a broader framework for fashioning semicrystalline PLA products with enhanced crystallinity and refined crystal structure towards prospective applications.

The tyrosine kinase inhibitor Nintedanib induces lysosomal dysfunctionality: Role of protonation-dependent crystallization processes

Nintedanib (NIN), a multi-tyrosine kinase inhibitor clinically approved for idiopathic pulmonary fibrosis and lung cancer, is characterized by protonation-dependent lysosomotropic behavior and appearance of lysosome-specific fluorescence emission properties. Here we investigate whether spontaneous formation of a so far unknown NIN matter within the acidic cell compartment is underlying these unexpected emissive properties and investigate the consequences on lysosome functionality. Lysosomes of cells treated with NIN, but not non-protonatable NIN derivatives, exhibited lysosome-associated birefringence signals co-localizing with the NIN-derived fluorescence emission. Sensitivity of both parameters towards vATPase inhibitors confirmed pH-dependent, spontaneous adoption of novel crystalline NIN structures in lysosomes. Accordingly, NIN crystallization from buffer solutions resulted in formation of multiple crystal polymorphs with pH-dependent fluorescence properties. Cell-free crystals grown at lysosomal-like pH conditions resembled NIN-treated cell lysosomes concerning fluorescence pattern, photobleaching dynamics, and Raman spectra. However, differences in birefringence intensity and FAIM-determined anisotropy, as well as predominant association with (intra)lysosomal membrane structures, suggested formation of a semi-solid NIN crystalline matter in acidic lysosomes. Despite comparable target kinase inhibition, NIN, but not its non-protonatable derivatives, impaired lysosomal functionality, mediated massive cell vacuolization, enhanced autophagy, deregulated lipid metabolism, and induced atypical phospholipidosis. Moreover, NIN exerted distinct phototoxicity, strictly dependent on lysosomal microcrystallization events. The spontaneous formation of NIN crystalline structures was also observable in the gut mucosa of orally NIN-treated mice. Summarizing, the here-described kinase inhibition-independent impact of NIN on lysosomal functionality mediates several of its cell biological activities and might contribute to NIN adverse effects.

Pickering Foam Stabilized by Diacylglycerol-Based Solid Lipid Nanoparticles: Effect of Protein Modification.

Pickering foams have great potential for applications in aerated foods, but their foaming ability and physical stability are still far from satisfactory. Herein, solid lipid particles (SLNs) were fabricated by using diacylglycerol of varying acyl chain lengths with modification by a protein. The SLNs showed different crystal polymorphisms and air-water interfacial activity. C14-DAG SLN with a contact angle ∼ 79° formed aqueous foam with supreme stability and high plasticity. Whey protein isolate and sodium caseinate (0.1 wt %) considerably enhanced the foamability and interfacial activity of SLNs and promoted the packing of particles at the bubble surface. However, high protein concentration caused foam destruction due to the competitive adsorption effect. β-sheet increased in protein after adsorption and changed the polymorphism and thermodynamic properties of SLN. The foam collapsing behaviors varied in the presence of protein. The results gave insights into fabricating ultrastable aqueous foams by using high-melting DAG particles. The obtained foams demonstrated good temperature sensitivity and plasticity, which showed promising application prospects in the food and cosmetic fields.

Comparison of two crystal polymorphs of NowGFP reveals a new conformational state trapped by crystal packing.

Crystal polymorphism serves as a strategy to study the conformational flexibility of proteins. However, the relationship between protein crystal packing and protein conformation often remains elusive. In this study, two distinct crystal forms of a green fluorescent protein variant, NowGFP, are compared: a previously identified monoclinic form (space group C2) and a newly discovered orthorhombic form (space group P212121). Comparative analysis reveals that both crystal forms exhibit nearly identical linear assemblies of NowGFP molecules interconnected through similar crystal contacts. However, a notable difference lies in the stacking of these assemblies: parallel in the monoclinic form and perpendicular in the orthorhombic form. This distinct mode of stacking leads to different crystal contacts and induces structural alteration in one of the two molecules within the asymmetric unit of the orthorhombic crystal form. This new conformational state captured by orthorhombic crystal packing exhibits two unique features: a conformational shift of the β-barrel scaffold and a restriction of pH-dependent shifts of the key residue Lys61, which is crucial for the pH-dependent spectral shift of this protein. These findings demonstrate a clear connection between crystal packing and alternative conformational states of proteins, providing insights into how structural variations influence the function of fluorescent proteins.

The rise and fall of adenine clusters in the gas phase: a glimpse into crystal growth and nucleation.

The emergence of a crystal nucleus from disordered states is a critical and challenging aspect of the crystallization process, primarily due to the extremely short length and timescales involved. Methods such as liquid-cell or low-dose focal-series transmission electron microscopy (TEM) are often employed to probe these events. In this study, we demonstrate that ion mobility spectrometry-mass spectrometry (IMS-MS) offers a complementary and insightful perspective on the nucleation process by examining the sizes and shapes of small clusters, specifically those ranging from n = 2 to 40. Our findings reveal the significant role of sulfate ions in the growth of adeninediium sulfate clusters, which are the precursors to the formation of single crystals. Specifically, sulfate ions stabilize adenine clusters at the 1:1 ratio. In contrast, guanine sulfate forms smaller clusters with varied ratios, which become stable as they approach the 1:2 ratio. The nucleation size is predicted to be between n = 8 and 14, correlating well with the unit cell dimensions of adenine crystals. This correlation suggests that IMS-MS can identify critical nucleation sizes and provide valuable structural information consistent with established crystallographic data. We also discuss the strengths and limitations of IMS-MS in this context. IMS-MS offers rapid and robust experimental protocols, making it a valuable tool for studying the effects of various additives on the assembly of small molecules. Additionally, it aids in elucidating nucleation processes and the growth of different crystal polymorphs.

Effect of acid type on biomineralization of soil using crude soybean urease solution

The one-phase-low-pH method is a simple, efficient, and user-friendly biogrouting technique that can effectively improve the biomineralization of enzyme-induced carbonate precipitation (EICP) using free urease enzyme. One of the most significant advantages of this method is its capacity to effectively delay calcium carbonate (CaCO3) precipitation by reducing the pH of the solution through the addition of acid. This prevents bioclogging during the biogrouting process and improves the biomineralization effect. However, the biomineralization of the one-phase-low-pH based EICP method may be influenced by the specific acid used. To investigate the impact of acid type on the one-phase-low-pH EICP method using crude soybean urease solution (CSUS), four types of acids, including hydrochloric acid (HCl), nitric acid (HNO3), acetic acid (CH3COOH), and lactic acid (C3H6O3), were used to adjust the pH of CSUS. A series of macroscopic and microscopic experiments were conducted to evaluate the effect of acid type on the one-phase-low-pH EICP method. The results indicate that the acid has an inhibition on the urease activity (UA) of CSUS. Among the acids tested, HNO3 exhibits the most pronounced inhibitory effect on the UA of CSUS, followed by HCl, and the least pronounced inhibitory effect for CH3COOH and C3H6O3 under the same pH conditions. Meanwhile, CH3COOH and C3H6O3 could provide a longer delay duration of CaCO3 precipitation than HNO3 and HCl. Therefore, the one-phase-low-pH EICP method based on CH3COOH and C3H6O3 can significantly improve the effective biocementation depth compared to that based on HNO3 and HCl. Nevertheless, the different types of acids appear to have no obvious effect on the polymorph and crystalline of the precipitated CaCO3 crystals.

Competing nucleation pathways in nanocrystal formation

Despite numerous efforts from numerical approaches to complement experimental measurements, several fundamental challenges have still hindered one’s ability to truly provide an atomistic picture of the nucleation process in nanocrystals. Among them, our study resolves three obstacles: (1) Machine-learning force fields including long-range interactions able to capture the finesse of the underlying atomic interactions, (2) Data-driven characterization of the local ordering in a complex structural landscape associated with several crystal polymorphs and (3) Comparing results from a large range of temperatures using both brute-force and rare-event sampling. Altogether, our simulation strategy has allowed us to study zinc oxide crystallization from nano-droplet melt. Remarkably, our results show that different nucleation pathways compete depending on the investigated degree of supercooling.

Highly aligned thin PVDF/Cloisite 30B nanofibers as a piezoelectric sensor

One-dimensional confined nanostructures with intense dipole orientation exhibit enhanced piezoelectric performance compared to traditional three-dimensional bulk films. Herein, we show that preparing highly aligned thin polyvinylidene fluoride (PVDF) nanofibers in the presence of a small amount of organically modified clay (Cloisite 30B) platelets induces a significant crystal polymorphism alteration from non-polar α-phase to polar β-phase rather than the randomly oriented neat PVDF nanofibers with a larger average diameter. It has been detected that the nanofiber orientation considerably contributes to the enhanced degree of crystallinity and mechanical properties. Also, the PVDF-Cloisite 30B interactions caused an improvement in the elastic modulus. The piezoelectric performance of the electrospun nanofibers was examined by sensing characteristics. It was found that the synergistic effects of nanofiber orientation and clay platelets efficiently improve sensing performance via the piezoelectric dipole orientation mechanism.