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Biomineralization is an important strategy for constructing mineral materials with excellent structure and properties. Organic biominerals exquisitely manipulate light, whereas inorganic biominerals are known for their mechanical strength. This progress report discusses the latest advances in the discovery and development of bioorganic molecules and crystalline materials, biomineralization mechanisms, the principles and theory of how ultrastructures produce optical properties, and relevant functional applications in biological and material fields. In particular, the discovery of bioorganic photonic crystalline materials has been remarkably extended from guanine alone to purines, pteridines, and flavins. Additionally, ultrastructural materials that function as light scatterers in living organisms were found to be produced by the nonclassical crystallization mechanism via amorphous precursors and oriented attachment. Further, the new biological function of the ultracompact reflector, composed of isoxanthopterin hollow nanospheres, was disclosed to dynamically adapt to various habitat environments. This report integrates materials and biological sciences to achieve a comprehensive view of organic biomineralization, inspiring the future development of advanced optical materials.

The ever-increasing demand for novel drug development has spurred the adaptation of conventional research methods in the era of artificial intelligence. Pharmaceutical crystallization, as an essential part of drug development, has become a thrilling research frontier that reduces screening labor via integrating automated high-throughput platforms with in situmonitoring and data-driven algorithms (e.g., machine learning) to predict physicochemical properties and various solid-state forms. In this review, we started with a primer to introduce the machine learning algorithms that are widely used in pharmaceutical crystallization. Then, we systematically summarized recent advancements on high-throughput platforms to acquire huge amounts of data sets, prediction of physicochemical properties based on abundant experimental data, optimization and monitoring of pharmaceutical crystallization process to screen crystallization conditions, and prediction of polymorphs and cocrystals. Finally, we discussed the challenges and opportunities in an endeavor to develop a fully automated pharmaceutical crystallization screening paradigm for ultimately realizing a self-driving screening laboratory. This review highlights the frontier of artificial intelligence in pharmaceutical crystallization and offers a guideline for beginners to not only understand the basic principles of machine learning algorithms but also learn how to utilize machine learning to accelerate pharmaceutical crystallization development.

Lithium hydroxide monohydrate (LHM) is an important lithium salt, which was widely used as the lithium source of cathode materials of the lithium battery. With the increasing global demand for lithium batteries, the market for LHM has expanded remarkably in recent years. However, LHM crystals are mostly flakes or needles with rough surfaces, strong hygroscopicity, and easy agglomeration, which is not conducive to storage and causes great product loss. Herein, we investigated the effect of various types of modifiers on the crystal growth modification and morphology modulation of LHM using a combination of crystallization experiments and density functional theory (DFT) calculations. Bulk LHM crystals were from a supersaturated solution of LHM, and the crystal morphology was indexed by single-crystal X-ray diffraction. Four types of potent modifiers were selected (including anionic surfactants, oxygen-rich polymers, hydroxyl-rich polymers, and carboxyl-rich polymers). The impact of various modifiers on the growth rate perpendicular to the (011) and (01̅1) surfaces was examined and evaluated through single-crystal growth experiments. TW20 and poly(ethylene glycol) (PEG) are potent inhibitors, and SDS and SLS serve as growth promoters. The action mechanisms of modifiers were revealed by binding specificity and DFT calculations through analyses of the surface electrostatic potential and adsorption energy. It was found that the electronegativity of the crystal surface plays an important role in determining the promotion or inhibition effect of selected modifiers. Our finding highlights the importance of electrostatic interactions in the screening of modifiers for inorganic salt crystals.

The heterojunction integration of two-dimensional (2D) materials via van der Waals (vdW) forces, unencumbered by lattice and processing constraints, constitutes an efficacious approach to enhance the overall optoelectronic performance of photodetectors, due to an assortment of distinctive light-matter interactions. Nonetheless, vdW heterojunction photodetectors based on transition metal dichalcogenides (TMDs) face an inevitable trade-off between low dark currents and high responsivity, curtailing the application potential of myriad novel optoelectronic components in sensing, spectral, and communication systems. In this study, we present the successful actualization of a highly sensitive, self-powered, and gate-tunable bipolar response photodetector. The mechanisms underlying photocurrent generation were scrutinized via bias-, power-, and position-dependent mapping photo-response measurements, identifying the photovoltaic effect, which is attributable to the Schottky junction’s built-in electric field, as the predominant mechanism. The prototype Au-WS2-graphene photodetector exhibits a remarkable light on/off ratio of 1.2 × 106, a specific detectivity of 6.12 × 1011cm Hz1/2W−1with 20 μs response time at 638 nm. The wide gate-tunable responsivity provides an adjustability scope, ranging from 0.9 to 3.1 A W−1. Notably, the device demonstrates an exceptional linear photo-current response, with a linear dynamic range (LDR) value approximating 130 dB, which significantly surpasses that of other photodetectors based on TMDs.

Unsaturated lipids containing different numbers and locations of C═C bonds are significantly associated with a variety of cellular and metabolic functions. Although matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has been used to visualize the spatial distribution patterns of various lipids in biological tissues, in situ identification, discrimination, and visualization of lipid C═C location isomers remain challenging. Herein, an efficient and fast on-tissue chemical derivatization (OTCD) approach was developed to pinpoint the locations of C═C bonds in complex lipids in situ via methyltrioxorhenium (MTO)-catalyzed epoxidation of C═C with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. The efficiency of OTCD could reach 100% via one-step spray deposition of the solution mixture of MTO/UHP/HFIP at room temperature. The developed OTCD method provided rich structural information on lipid C═C location isomers, and their accurate spatial distribution patterns were resolved in mouse brain tissues. Tissue-specific distributions and changes of lipid C═C location isomers in the liver sections of obese ob/oband diabetic db/dbmice were further investigated, and their correlation in two animal models was revealed. The simplicity and high efficiency of the OTCD method developed for MALDI tandem MSI of lipid C═C location isomers possess great potential for functional spatial lipidomics.

Interactions between molecular modifiers and crystal surfaces govern numerous processes and structural outcomes of natural, biological, and synthetic crystallization. An efficient method of tailoring modifier–crystal interactions involves the design of imposters with structures and chemical functionalities that closely match those of the solute with subtle changes that preserve molecular recognition for modifier binding to crystal surfaces. Modifiers can function as inhibitors, promoters, or combinations of both to alter processes of crystal nucleation and growth. Here, we examine molecular modifiers that perturb the crystallization of ammonium urate (NH4HU), a pathological component of kidney stones, and a model system for assessing modifier–crystal interactions. Bulk crystallization assays were used to identify effective inhibitors and promoters of NH4HU crystallization. Two potent inhibitors, methyluric acid (MA) and poly(ethyleneimine) (PEIM), were identified where PEIM completely suppresses crystal growth at concentrations above 1.0 μg/mL, and MA displays a maximum growth inhibition of 60%. Time-resolved studies using a combination of microfluidics and atomic force microscopy elucidated the mechanisms by which each modifier influences layer generation and spreading on crystal surfaces. We used these techniques for select modifiers to quantify their effects on the anisotropic rates of crystallization and concomitant impact on crystal size and morphology. In situ characterization revealed that subtle changes in modifier functionality determine whether these imposters operate by either step pinning or kink blocking mechanisms. We demonstrated that molecular imposters of NH4HU crystallization operate by multiple, and sometimes opposing, roles of promotion and inhibition depending on the judicious selection of growth conditions. Collectively, our findings uncover trends among molecular imposters that are unique in relation to previously reported cases of crystal growth modification.

In the long history of investigation of herbal products, microscopic examination has greatly contributed to the authentication of herbs in a powder form. However, it cannot provide the chemical profiles of herbal powders and thus is limited to morphological identification. In this work, we present a label-free and automatic approach for the characterization and identification of single herbal powders and their adulterants, enabled through the combination of microscopy-guided auto-sampling and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). To meet the demand for automatic and highly efficient in situ extraction, the glass slide was coated with gelatin to immobilize dried herbal powders that cannot stick to the glass slide like fresh and hydrated cells. The gelatin coating also facilitated the pump-out of chemical components and prevented diffusion across the interface enabled by the formation of a tight contact at the probe tip and surface. Optical microscopy was applied to acquire the microstructure and position of the herbal powders immobilized on the gelatin-coated slide. The candidate single herbal powders were picked out by a software for subsequent auto-sampling and MALDI MS identification. The combination of microstructure features and chemical profiles significantly improved the authentication capability of microscopic examination.

The demand for broadband, room-temperature infrared, and terahertz (THz) detectors is rapidly increasing owing to crucial applications in telecommunications, security screening, nondestructive testing, and medical diagnostics. Current photodetectors face significant challenges, including high intrinsic dark currents and the necessity for cryogenic cooling, which limit their effectiveness in detecting low-energy photons. Here, we introduce a high-performance ultrabroadband photodetector operating at room temperature based on two-dimensional black arsenene (b-As) nanosheets. This device demonstrates responsivity across visible, near-infrared, and THz spectral ranges, with responsivities reaching 91.6 A/W at 520 nm, 6.3 A/W at 1550 nm, and 7.8 V/W at 0.27 THz. The exceptional THz responsivity is attributed to the use of plasma-wave rectification in antenna-integrated field-effect transistors with asymmetric antennas, enhancing light-matter interaction and facilitating nonlinear rectification within the two-dimensional electron gas of the transistor channel, achieving a voltage-dependent bipolar response. These advanced b-As-based photodetectors also enable secure THz communication through complex logic operations, achieving robust data encryption and high-performance signal processing.

The development of high specific capacitance electrode materials with high efficiency, scalability and economic feasibility is significant for the application of supercapacitors, however, the synthesis of electrode material still faces huge challenges. Herein, graphene(G)/Fe2O3nanocomposite was prepared viaa simple hydrothermal method connected with subsequent thermal reduction process. Scanning electron microscopy(SEM) and transmission electron microscopy(TEM) results showed rod-like Fe2O3nanoparticles were prepared and well-dispersed on graphene layers, providing a rich active site and effectively buffering the aggregation of Fe2O3nanoparticles in the process of electrochemical reaction. The specific capacitance of the obtained G/Fe2O3nanocomposite as negative electrode for supercapacitor was 378.7 F/g at the current density of 1.5 A/g, and the specific capacitance retention was 88.76% after 3000 cycles. Furthermore, the asymmetric supercapacitor(ASC) was fabricated with G/Fe2O3nanocomposite as negative electrode, graphene as positive electrode, which achieved a high energy density of 64.09 W·h/kg at a power density of 800.01 W/kg, maintained 30.07 W·h/kg at a power density of 8004.89 W/kg, and retained its initial capacitance by 78.04% after 3000 cycles. The excellent result offered a promising way for the G/Fe2O3nanocomposite to be applied in high energy density storage systems.

The four-quadrant regimes of attainable polymorph crystallization (FQR-APC) plot was recently developed through numerical simulations of crystallization kinetics of a dipolymorphic system. Retraction in the polymorphic composition of the most stable form in crystallized samples was unveiled a characteristic indication of concomitant polymorphism. Comparisons were made with a recently developed concept, the Ostwald ratio (OR), in light of characterization of polymorphic formation. It was shown that both schemes display a good agreement in describing polymorphic outcomes, despite their distinct theoretical origins.

[Display omitted] • A preferential crystallization process of norvaline performed near the eutectic composition was established. • Additive-assisted preferential crystallization boosts purity up to 98% with 56% yield. • Tailor-made additives selectively suppress crystallization of racemate not enantiomer. • Molecular mechanism of selective inhibition by tailor-made additives was elucidated. Herein, we report a successful resolution of L-norvaline, a racemic compound system, performed near the eutectic composition by coupling preferential crystallization with tailor-made additives. The structures of enantiomer and racemate were characterized by PXRD, DSC, and the enantiomeric purity were measured by Chiral HPLC. The preferential crystallization process was designed and established from binary melting phase diagram and ternary solution phase diagram. The effects of supersaturation, solution enantiomer composition, and seed quantity on the preferential crystallization process were investigated. However, the significant improvements of enantiomeric purity and product yield were demonstrated by additive-assisted preferential crystallization approach using tailor-made additives. These additives bearing similar structure motifs to norvaline a highly selective binding to the racemate rather than enantiomer and remarkably suppress nucleation of DL-norvaline, the key factor determining the resultant enantiomer purity and separation efficiency. The underly inhibition principle was revealed due to the centrosymmetric packing of the racemate while the polarity of enantiomer leads to only partial or slight crystallization suppression. The interesting inhibition mode by tailor-made additives is also believed to be applicable for other racemic crystallization systems. Our established additive-assisted preferential crystallization has showed great potential in the development of separation technology and resolution of enantiomer from racemic compounds. [ABSTRACT FROM AUTHOR]

Advances in nano-lubricant additives are vital to the pursuit of energy efficiency and sustainable development. Carbon dots (CDs) have been widely investigated in the domain of lubricant additives owing to their extraordinary tribological properties, in particular, their friction-reducing and anti-wear properties. Metal-doped CDs are a new type of CDs, and their friction-reducing and anti-wear properties are attracting increasing attention. Therefore, a series of CDs doped with various divalent metal ions have been successfully synthesized via one-pot pyrolysis. The tribological properties of the synthesized CDs as water-based lubricant additives are in the following order: Zn-CDs > Cu-CDs ≫ Mg-CDs > Fe-CDs > U-CDs. Specifically, adding 1.0 wt% of Zn-CDs into water-based lubricant results in 62.5% friction and 81.8% wear reduction. Meanwhile, the load-carrying capacity of the water-based lubricant increases from 120 N to at least 500 N. Zn-CDs as an additive have long service life. Additionally, anion-tuned Zn-CDs fabricated via anion exchange exhibit promise as lubricant additives for poly(ethylene glycol). Based on the results of wear scar surface analyses, it is discovered that tribochemical films, primarily composed of iron oxides, nitrides, metal carbonates, zinc oxides, zinc carbonates, organic compounds, and embedded carbon cores, formed on the rubbing surfaces with a thickness of approximately 270 nm when Zn-CDs are used as additives. This film combined with the “ball-bearing” and third-particle effects of Zn-CDs contributed to excellent lubrication performance.

ABSTRACTChemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC.

ABSTRACTBreast cancer (BC) is regarded as the major cause of cancer-associated deaths in women. Paclitaxel exerts a critical impact on the chemotherapy of BC, but the resistance to paclitaxel becomes a great obstacle in treating the disease. It is reported that noncoding RNA nuclear receptor binding SET domain protein 1 (NSD1) plays a significant role in drug resistance; however, the special role of NSD1 in paclitaxel-resistant BC is unclear. Human BC cell line MCF-7 was used to establish paclitaxel-resistant BC cells (MCF-7/PR). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) displayed that NSD1 and F-box and leucine-rich repeat protein 11 (FBXL11) were highly expressed in BC tissues. Western blotting was utilized for protein level assessment. Cell counting kit-8 (CCK-8), Transwell, wound healing assays, and animal experiments were conducted to examine the influence of NSD1 or FBXL11 on the malignant behaviors of BC in vitroand in vivo, respectively. Transfected MCF-7/PR cells were injected subcutaneously into BALB/c nude mice with or without treatment of paclitaxel. The nuclear factor kappa B (NF-kB) activity was evaluated by the luciferase reporter assay. Results showed that NSD1 knockdown inhibited the epithelial-mesenchymal transition (EMT), migration and invasiveness of BC in vitro, which was rescued by FBXL11 overexpression. Furthermore, NSD1 silencing promoted paclitaxel sensitivity of paclitaxel-resistant BC cells and suppressed tumor growth and paclitaxel resistance in vivo. NSD1 knockdown reduced NF-kB activity, while FBXL11 inhibition markedly increased NF-kB activity. Collectively, NSD1 facilitates the EMT, migration and invasion in paclitaxel-resistant BC cells via regulating NF-kB and FBXL11.

Black phosphorus quantum dots (BPQDs), obtained via a typical solution-based top-down method, were used as water-based lubricant additives. BPQDs exhibited remarkable friction reduction and anti-wear properties even at the ultra-low concentration of 0.005 wt%, which reduced the friction coefficient and wear volume of the base liquid by 32.3% and 56.4%, respectively. In addition, the load-supporting capacity of the base liquid increased from 120 N to over 300 N. BPQDs-based additives exhibited a relatively long lifetime at a relatively high load of 80 N. The performance of BPQDs considerably exceeded that of the BP; this may be attributed to their small and uniform particle size, good dispersion stability in water, and high reactivity at the frictional surfaces. The results of the surface wear resistance analysis demonstrated that a robust tribochemical film with a thickness of approximately 90 nm was formed on the rubbing surface lubricated with 0.005 wt% of BPQDs dispersion. Moreover, the film served as a direct evidence of the excellent tribological performance of BPQDs.

The solubility of 2-ethoxybenzamide was measured in 12 pure solvents, namely, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, ethyl formate, methyl acetate, propyl acetate, n-butyl acetate, N, N-dimethylformamide, 1,4-dioxane, acetone, and 2-butanone from 288.15 to 328.15 K at atmospheric pressure by the gravimetric method. The solubility of 2-ethoxybenzamide in all 12 pure solvents increases monotonically with temperature. The highest solubility value was found in N, N-dimethylformamide, while the lowest one was found in n-butyl acetate. Among various investigated influence factors such as solvent polarity, hydrogen bond donor propensity, hydrogen bond acceptor propensity, and cohesive energy density, the polarity of solvent was found to play a major role in 2-ethoxybenzamide solubilities. Furthermore, the λhequation, van’t Hoff equation, and modified Apelblat equation were employed to correlate the solubility data of 2-ethoxybenzamide, where the modified Apelblat equation displayed the best fitting performance.

Development of superparamagnetic iron oxide nanoparticles (SPIONs) based theranostics has suffered due to its self-contradictory requirements on water dispersity and drug loadings. Generally well-dispersed SPIONs have excellent MRI performance but are insensitive to magnetism mediated delivery. Besides, loading hydrophobic drugs also hampers the stability of SPIONs which is critical for their biomedical applications. Considering these aspects, we employed curcumin as a cross-linking agent to facilitate the modular assembly of drug and monodisperse SPIONs (Cur/ALN-β-CD-SPIONs). Interestingly, the saturation magnetization of Cur/ALN-β-CD-SPIONs is higher than that of ALN-β-CD-SPIONs, and the value of r2indicating the negative contrast ability increases to 389.96 mM–1s–1. Furthermore, the Cur/ALN-β-CD-SPIONs are very stable in PBS buffer over 3 weeks. The mice treated with Cur/ALN-β-CD-SPIONs by tail vein injection displayed a better tumor inhibition effect than that of free curcumin. This study provides a simple method for modular assembly of drug and monodisperse SPIONs, which is crucial to the design of SPIONs with superior T2-imaging performance and drug delivery.

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry (MS) has become an attractive complementary approach to matrix-assisted laser desorption/ionization (MALDI) MS. SALDI MS has great potential for the detection of small molecules because of the absence of applied matrix. In this work, a functionalized porous TiO2film immobilized with gold nanoparticles (AuNPs-FPTDF) was prepared to enhance SALDI MS performance. The porous TiO2films were prepared by the facile sol–gel method and chemically functionalized for dense loading of AuNPs. The prepared AuNPs-FPTDF showed superior performance in the detection and imaging of small molecules in dual-polarity modes, with high detection sensitivity in the low pmol range, good repeatability, and low background noise compared to common organic MALDI matrixes. Its usage efficiently enhanced SALDI MS detection of various small molecules, such as amino acids and neurotransmitters, fatty acids, saccharides, alkaloids, and flavonoids, as compared with α-cyano-4-hydroxycinnamic acid, 9-aminoacridine, and the three precursor substrates of AuNPs-FPTDF. In addition, the blood glucose level in rats was successfully determined from a linearity concentration range of 0.5–9 mM, as well as other biomarkers in rat serum with SALDI MS. More importantly, the spatial distribution of metabolites from the intact flowers of the medicinal plant Catharanthus roseuswas explored by using the AuNPs-FPTDF as an imprint SALDI MS substrate in dual-polarity modes. These results demonstrate wide applications and superior performances of the AuNPs-FPTDF as a multifunctional SALDI surface with enhanced detection sensitivity and imaging capabilities.

Reactive crystallization (RC) of vortioxetine hydrobromide (VH) in four solvents was investigated in this work. In solvents with strong hydrogen bond acceptor capacity, the thermodynamics stable form B is preferred and the conversion rate from form A to form B increases. Meanwhile, supersaturation (S) is also an important factor affecting the polymorphic behavior. When supersaturation is high, the metastable form A is preferred, while the conversion rate also increases. Solubility data and nucleation rate were adopted to explain thermodynamic and kinetic reasons for solvent and supersaturation effects here. In addition, RC process in the four solvents at 313.15 K (SB≈ 5.60) was detected by online attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and offline power X-ray diffraction (PXRD). Results show that the effect of reaction kinetics on polymorph formation of VH can be ignored and nucleation and growth of form B is the controlling step of subsequent suspension polymorphic conversion process.

Poor solubility and dissolution property of pharmaceuticals largely limits their bioavailability and efficacy, and development of a multicomponent crystal is one of the effective approaches to potentially address the issue. Herein we investigated the structure and property relationship of multicomponent crystal aiming to improve the pharmaceutical property, using the Biopharmaceutics Drug Disposition Classification System class II antipsychotic drug Aripiprazole (APZ) as model compound. We reported six new discovered multicomponent crystals of APZ salts with all pharmaceutically acceptable coformers. The comprehensive characterizations were done using X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS) techniques. Four multicomponent crystals were structurally solved for the first time by single-crystal X-ray diffraction, demonstrating the proton transfer from the carboxyl group of acids to APZ piperazine. Molecular interactions, crystal packing, and structure similarity analyses performed by Hirshfeld surface and CrystalCMP confirmed the charge-assisted H-bonding sites and structural similarity among the solved crystal structures. The XPS characterization of the other two multicomponent crystals corroborates the salt form as evidenced by the significant chemical shift toward higher binding energy; the pharmaceutical properties including stability, hygroscopicity, and dissolution behavior of all multicomponent crystals were examined by dynamic vapor sorption and high-performance liquid chromatography. It was found all six multicomponent crystals display high stability and low hygroscopicity but divergent dissolution behavior. The variations of these physicochemical properties were further rationalized from their crystal structures and intermolecular interactions.

The therapeutics for nephrolithiasis have created an awareness of the potential effects of crystal modifiers on the biocrystallization process. The crystallization of calcium oxalate, a primary constituent of kidney stones, is confirmed to be inhibited by natural or synthetic modifiers, but the induction of calcium oxalate dihydrate and trihydrate, which is likewise effective for retardation of stone formation, is rarely focused on. Herein, we performed a systematic investigation of the effect of gallic acid, a natural polyphenol, on the nucleation of calcium oxalate from both experimental and simulation approaches. Our results reveal that the solution species of gallic acid alter the nucleation pathways of calcium oxalate and induce the formation of different types of amorphous structures corresponding to calcium oxalate hydrates. Different species of gallic acid regulate the formation of three types of amorphous calcium oxalates (ACOs) by incorporating the proper water contents and specific interactions. Fluorescence microscopy further demonstrates clearly the incorporation of gallic acid in the nucleated calcium oxalate precipitates. These findings unveil the nucleation mechanism of different calcium oxalate hydrates with the inclusion of modifiers and provide insights for an understanding of stone formation and its potential inhibitors.

Metastable zone widths (MSZWs) are one of the crucial parameters in solution crystallization process optimization whose accuracy would determine the crystalline product quality and process robustness. In this paper, the MSZWs of lithium carbonate-reactive crystallization were measured by turbidity technology during the reactive crystallization process of Li2CO3. Three semiempirical models were used to proceed with the prediction of MSZWs, and further, artificial neural networks (ANN) were introduced for the first time to predict MSZWs and compared with semiempirical models. Then, the prediction models were evaluated by the indicators root mean square error (RMSE), R2, mean absolute percentage error (MAPE), and cp. The results indicated that the ANN model has the best prediction accuracy. An orthogonal-dataset-trained ANN model was developed and evaluated, and it showed the highest efficiency and the second-best accuracy. In addition, the effects of process parameters on the MSZWs were investigated and analyzed, including Li2SO4concentrations, working volumes, agitation speeds, impurities, temperatures, and Na2CO3feed speeds and concentrations. The results showed that temperatures and concentrations had a strong positive correlation with MSZWs, and temperature is the most sensitive parameter that is recommended for MSZWs-based crystallization process optimization.

Detection of two or multiple polymorphs in solution is a result of concomitant polymorphism or due to solvent-mediated phase transition. In this work, crystallization of tolfenamic acid (TFA) was conducted under several different supersaturation and temperature conditions. Form I and form II were identified from crystallized samples. Solute concentration and polymorph composition were respectively determined by UV–vis and Raman spectroscopy through the course of crystallization. Kinetic modeling was also conducted to further examine the crystallization kinetics, revealing that the observed simultaneous nucleation of the two forms is characteristically associated with an intermediate recession of the relative amount of form I in crystal mixtures. This unambiguous kinetic event proves to be indicative of the concomitant crystallization of TFA, shedding light on its nucleation mechanism.

Gout is a kind of severe joint disease caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. Numerous studies have focused on the influences of the components in synovial fluid on the nucleation of MSUM in solution. Yet little is known about the pathological pathway of MSUM crystallization in vivo. Herein, the pathological crystallization pathway of MSUM was investigated in a simulated biological environment (0.15 M Na+and pH 7.40 buffer). Optical and electron microscope images in combination with powder X-ray diffraction demonstrated that the formation of MSUM involves three stages of molecular aggregation to form fibril-like amorphous subunits, the agglomeration of these nanosized subunits, and the phase transition from amorphous to filamentous crystals. Further, Fourier transform infrared spectroscopy and Raman spectra show that the filamentous crystals bear a structure extremely similar to that of amorphous agglomerates. However, the amorphous form contains more water content in comparison to that of MSUM crystals, as unveiled by thermal analyses. The time-resolved dynamic light scattering and small-angle X-ray scattering data reveal the formation of fibril-like nanoprecursors in the early stage of nucleation and the structure evolution over time. Thus, a nonclassical crystallization mechanism for MSUM in a simulated joint environment was proposed.