Search

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.

A novel one‐pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α‐diphenyl‐2‐pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)‐enantiomer and (2S,3S)‐enantiomer in solution, achieving a one‐pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)‐carprofen, (R,S)‐indoprofen, and (R,S)‐indobufen. The one‐pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization‐induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy. [ABSTRACT FROM AUTHOR]

Crystal nucleation determining the formation and assembly pathway of first organic materials is the central science of various scientific disciplines such as chemical, geochemical, biological, and synthetic materials. However, our current understanding of the molecular mechanisms of nucleation remains limited. Over the past decades, the advancements of new experimental and computational techniques have renewed numerous interests in detailed molecular mechanisms of crystal nucleation, especially structure evolution and solution chemistry. These efforts bifurcate into two categories: (modified) classical nucleation theory (CNT) and non-classical nucleation mechanisms. In this review, we briefly introduce the two nucleation mechanisms and summarize current molecular understandings of crystal nucleation that are specifically applied in polymorphic crystallization systems of small organic molecules. Many important aspects of crystal nucleation including molecular association, solvation, aromatic interactions, and hierarchy in intermolecular interactions were examined and discussed for a series of organic molecular systems. The new understandings relating to molecular self-assembly in nucleating systems have suggested more complex multiple nucleation pathways that are associated with the formation and evolution of molecular aggregates in solution. [ABSTRACT FROM AUTHOR]

Ostwald's rule of stages is one of the most important empirical rules to understand the crystallization behavior of crystalline materials, however, it may not be always satisfied. Herein, we demonstrate that crystallization outcomes of citric acid (CA) in aqueous solutions violate this rule. The anhydrous phase was found to nucleate at the whole temperature range (below or above the transition point of the system), whereas, the monohydrate form only nucleated at high supersaturation below the transition point. The unexpected appearance of the anhydrous phase is shown to have been influenced by solution ionization and its crystallization kinetic advantage over the monohydrate form. [ABSTRACT FROM AUTHOR]

In this paper, the crystallization of L-glutamic acid with application of ultrasound was explored in detail, including the process of nucleation, polymorphic control and polymorphic transformation. The induction time and metastable zone widths (MSZWs) were measured with and without ultrasound during the nucleation process. The induction time and MSZWs were decreased by ultrasound and the induction time was further decreased by higher ultrasonic power. The calculated nucleation parameters (such as interfacial energy, critical nucleus size and critical Gibbs energy) showed an obvious decrease in the presence of ultrasound, indicating that the nucleation was enhanced with application of ultrasound. By adjusting the ultrasonic power in the quench cooling process, the difference in nucleation temperatures would determine the distribution of polymorphs. In further, the polymorphic transformation was investigated quantitatively, and to the best of our knowledge, it was the first time to study the transformation kinetics with ultrasound using Avrami-Erofeev model. In the transformation process, the crystallization mechanism of the stable form was modified by ultrasound. The ultrasound eliminated the nucleation element in the rate-limiting step and facilitated the crystal growth of stable form. Thus, the ultrasound has a profound influence on L-glutamic acid crystallization. [ABSTRACT FROM AUTHOR]

The reactive crystallization of lithium carbonate (Li2CO3) from lithium sulfate (Li2SO4) and sodium carbonate (Na2CO3) solutions is a key process in harvesting solid lithium, whether from ores, brines, or clays. However, the process kinetics and mechanism remain poorly understood and the modelling of the reactive crystallization of Li2CO3 is not available. Hence, this work aims to determine the kinetics and mechanisms of the nucleation and growth of Li2CO3 reactive crystallization by induction time measurements and to model and optimize the crystallization process using response surface methodology. Induction time measurements were carried out as functions of initial supersaturation and temperature using a laser method. It was found that the primary nucleation mechanism of Li2CO3 varies with solution supersaturations, in which, expectedly, the heterogenous nucleation mechanism dominates at low supersaturations while the homogeneous nucleation mode governs at high supersaturations. The transition point between heterogenous and homogenous nucleation was found to vary with temperatures. Growth modes of Li2CO3 crystals were investigated by relating induction time data with various growth mechanisms, revealing a two-dimensional nucleation-mediated growth mechanism. The modelling and optimization of a complex reactive crystallization were performed by response surface methodology (RSM), and the effects of various crystallization parameters on product and process performances were examined. Solution concentration was found to be the critical factor determining the yield of crystallization, while stirring speed was found to play a dominant role in the particle size of Li2CO3 crystals. Our findings may provide a better understanding of the reactive crystallization process of Li2CO3 and are critical in relation to the crystallization design and control of Li2CO3 production from lithium sulfate sources. [ABSTRACT FROM AUTHOR]

The important intermediate thiothiamine for Vitamin B1 production is often challenged by issues related to mixed polymorphs and needle-shaped crystal morphology in industrial production. These challenges can be effectively addressed through crystal engineering strategies. In this study, the key factors affecting the crystal form were investigated in reactive crystallization. Subsequently, the reactive crystallization process was monitored online using in-situ ATR-FTIR and FBRM techniques. It was determined that crystallization process is the rate-limiting step throughout the reactive crystallization process. Various factors affecting the crystal morphology were identified. Through process control and optimization, a product was achieved with a filtration time reduced by over 60% and a moisture content reduction of >20%. Overall, this study provides valuable insights from a crystal engineering perspective to address the poor powder properties. [Display omitted] • Identified the thiothiamine crystal form I and II as enantiotropic polymorph. • The key factors affecting the crystal form were determined. • The high reaction temperature helps to optimize the crystal morphology. • The co-optimization of crystal morphology and crystal form was realized. [ABSTRACT FROM AUTHOR]

[Display omitted] • The molecular mechanism of oiling-out phenomenon was proposed. • Solute dimers are emphasized to be the key factor in oiling-out. • A new prediction method was established for phase diagram of oiling-out. • The oiling-out curves and solvent systems of the five substances were predicted. • The purity of pyraclostrobin was significantly increased from 42.76% to 99.32%. Oiling-out is a unique liquid–liquid phase separation phenomenon in solution crystallization. The unknown microscopic mechanism of oiling-out makes it difficult to control and significantly reduces the separation efficiency. In this work, an adsorption–desorption mechanism of temperature-driven molecular clustering is proposed based on the configuration search and the transformation process monitoring of dimers. This mechanism indicates that the stable and sufficient solute dimers in the solvent is the key condition for inducing oiling-out, accompanied by the transformation among various dimer configurations. Based on this mechanism, a prediction method of oiling-out phase diagram has been established through configurational stability analysis and determination of the total energy-temperature curve. This prediction method has been successfully applied to five systems: pyraclostrobin, vanillin, ethyl vanillin, citric acid, and benzoic acid. Importantly, the purity of pyraclostrobin is increased from 42.76% to 99.32% with the assistance of the oiling-out phase diagram. These findings not only provide advanced insights into understanding and controlling oiling-out during crystallization, but also highlight the role that oiling-out plays in the molecular assembly process of crystal nucleation. [ABSTRACT FROM AUTHOR]

Inorganic nanofillers have sparked important research in the field of polymer nanocomposites because they can improve the properties of polymers. Hydrophobic ZnO nanoparticles modified by oleic acid (OA) were designed and prepared to accelerate the dispersion state of ZnO in the high viscosity polyethylene (HDPE), and enhance the performance of HDPE. HDPE/ZnO nanocomposites with different kinds and fractions of ZnO were further prepared via melt mixing method. The result showed the hexagonal and spindle-like ZnO nanoparticles with size distribution of 150–300 nm was acquired in the absence and presence of OA. Compared with surface untreated ZnO (U-ZnO), ZnO nanoparticles modified by OA (O-ZnO) can disperse evenly into HDPE at the fraction of O-ZnO below 5 wt%. TG data showed the presence of nanosized U-ZnO and O-ZnO in HDPE can significantly enhance the thermal stability of HDPE through raising the activation energy of HDPE in thermal decomposition process. The thermal decomposition order (n) for HDPE/ZnO nanocomposites was mostly bigger than that of HDPE, demonstrating the decomposition mechanism for HDPE became more complicated because of the addition of ZnO nanoparticles. DSC data showed U-ZnO nanoparticles cannot accelerate nucleation of HDPE and seemed to postpone the crystallization process, and O-ZnO nanoparticles was heterogeneous nucleating agent for HDPE. Moreover, the tensile and impact strength of HDPE was improved by the addition of O-ZnO, and connected with the dispersion state of ZnO nanoparticles in HDPE. The improvement in thermal stability, crystallization and mechanical properties by adding ZnO into HDPE matrix significantly enhance the potential of HDPE in food packaging, electronic packaging, drug and pharmaceutical bottles. [Display omitted] [ABSTRACT FROM AUTHOR]

Kidney stones is one of the common diseases of the urinary system. The primary cause of kidney stone formation is the thermodynamic supersaturation of lithogenic solutes in urine, which desaturates by nucleation, crystal growth and aggregation of minerals and salts, mainly Calcium oxalate (CaOx). One of the potential therapies is to develop drug molecules to inhibit or prevent CaOx crystallization in urine. Traditional Chinese medicines (TCMs) provided an efficient approach for the treatment of kidney stones with a specialized-designed recipe of medicinal herbs. But the action details of these herbs were poorly understood due to their complex components, and whether the effective constituents of herbs have an inhibitory effect on the process of stone formation has not been evaluated. This study aims to develop and identify inhibitor substitutes from a library of kidney stone prescriptions in traditional Chinese medicines to prevent pathological kidney stone formation. As many as twenty Chinese medicines were extracted and separated into five different polar extracts, the inhibition performance of which on CaOx crystallization was explored by recording and comparing crystallization kinetics. The potential inhibitor molecules in the inhibitory extracts were confirmed by HPLC and their retardation efficacy was evaluated by quantifying nucleation and growth kinetics using colorimetry. Then the inhibitor-COM crystal interactions and specificity were examined by morphology evolution and surface structure analysis. In vitro inhibition performance of inhibitors on crystal growth and attachment of CaOx crystals to human renal epithelial cells were further evaluated by recording the nucleation and adhesive crystal numbers. Water- and n-butanol- soluble extracts from 20 kinds of herbs show almost 100% inhibition percentage, and the n-butanol extracts was found better than commercial drug citrate. Twenty-one molecule substitutes were identified from these extracts, and among them polyphenols display the best inhibition efficacy to retard CaOx crystallization. The high-throughput colorimetric assay and morphology examinations reveals thirteen out of 21 molecules show inhibition potential and disrupt growth of CaOx monohydrate crystals by interacting with exposed Ca2+ and C 2 O 4 2− on the (100) and (010) surfaces. Moreover, these inhibitors also display pronounced performance in protecting renal epithelial cells by inhibiting nucleation and adhesion of CaOx crystals to cells, thus reducing stone formation. The structure-performance correlation among 19 screened molecules that inhibitors having pKa<3.5, logD (pH = 6) <0, H-number>0.1 mmol are the best in suppressing CaOx crystallization. Our findings provide a novel solution to design and manufacture inhibitor drugs from Chinese medicines for preventing pathological kidney stones formation. [Display omitted] • Discovering inhibitor substitutes for CaOx stones crystallization from traditional Chinese medicines. • Water and n-butanol soluble extracts from 20 Chinese medicines are the most efficient inhibitors for CaOx crystallization. • Phenolic compounds in these extracts were discovered to inhibit dramatically CaOx crystallization. • Anti-adhesive ability of these inhibitors indicates the pronounced efficacy on reduction of stones formation. • Structure-performance relationship of substitutes shows pKa and H-number of inhibitors determining the inhibition efficacy. [ABSTRACT FROM AUTHOR]

• A strategy for rationally selecting solvent systems of spherical agglomeration. • Wettability is emphasized to be the key role in spherical agglomeration. • Wetting and adhesion were studied by the Lifshitz-van der Waals acid-base approach. • New solvent systems were selected by the strategy for diverse substances. A strategy for rationally selecting solvent systems of spherical agglomeration is proposed for the first time. It emphasizes that followed by crystallization and phase separation, spherical agglomeration can be achieved only when the solvent system can induce wetting and adhesion which are estimated by the Lifshitz-van der Waals acid-base approach. Especially for wettability of bridging liquid, solvent and anti-solvent, the strategy indicates that it is of great importance for a successful solvent system. Valid systems therefore are selected in the first place while invalid ones are removed effectively according to the wettability difference. Based on the strategy, valid solvent systems for cefotaxime sodium and benzoic acid spherical agglomeration were selected successfully from 720 and 2184 systems respectively without missing the reported systems. The strategy also predicted no valid systems for potassium chloride, maltitol and trisodium phosphate in the given solvent combinations, which agreed with the experiment results. [ABSTRACT FROM AUTHOR]