Insight into the Manipulation Mechanism of Polymorphic Transformation by Polymers: A Case of Cimetidine.

PURPOSE: Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations. METHODS: The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations. RESULTS: The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute-solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively. CONCLUSION: PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed.

Trimodal operation of a robust smart organic crystal.

We describe a dynamic crystalline material that integrates mechanical, thermal, and light modes of operation, with unusual robustness and resilience and a variety of both slow and fast kinematic effects that occur on very different time scales. In the mechanical mode of operation, crystals of this material are amenable to elastic deformation, and they can be reversibly morphed and even closed into a loop, sustaining strains of up to about 2.6%. Upon release of the external force, the crystals resume their original shape without any sign of damage, demonstrating outstanding elasticity. Application of torque results in plastic twisting for several rotations without damage, and the twisted crystal can still be bent elastically. The thermal mode of operation relies on switching the lattice at least several dozen times. The migration of the phase boundaries depends on the crystal habit. It can be precisely controlled by temperature, and it is accompanied by both slow and fast motions, including shear deformation and leaping. Parallel boundaries result in a thermomechanical effect, while non-parallel boundaries result in a thermosalient effect. Finally, the photochemical mode of operation is driven by isomerization and can be thermally reverted. The structure of the crystal can also be switched photochemically, and the generation of a bilayer induces rapid bending upon exposure to ultraviolet light, an effect that further diversifies the mechanical response of the material. The small structural changes, low-energy and weak intramolecular hydrogen bonds, and shear deformation, which could dissipate part of the elastic energy, are considered to be the decisive factors for the conservation of the long-range order and the extraordinary diversity in the response of this, and potentially many other dynamic crystalline materials.

Photo/Mechanical/Acidic Multi-Stimuli Responses and Information Encryption Design of Acylhydrazone Derivative.

Stimuli-responsive crystalline materials have received much attention for being potential candidates of smart materials. However, the occurrence of polymorphism-driven stimuli responses in crystalline materials remains interesting but rare. Herein, three polymorphs of an acylhydrazone derivative, N'-[(E)-(1-benzofuran-2-yl) methylidene] pyridine -4-carbohydrazide (BFMP) were prepared. Form-1 undergoes a photomechanical response via E→Z photoisomerization under UV irradiation, accompanied by a decrease in fluorescence intensity and a change from colorless to yellow. Two types of Z→E thermal isomerization mechanisms with significant differences in conversion rate were observed at different temperatures in form-1. The solid-melt-solid transition has a faster conversion rate compared to the solid-solid transition due to freedom from lattice confinement. The transition from form-2 to form-3 can be achieved under grinding, coupled with a significant decrease in fluorescence intensity. The similar molecular stacking pattern of form-2 and form-3 provides a structural basis for the grinding-induced crystalline transition behavior. In addition, the presence of the pyridine moiety imparts an acidochromic property. The combination of photochromism and acidochromism explores the possible applications of acylhydrazone derivatives in information encryption.

Non-destructive real-time monitoring and investigation of the self-assembly process using fluorescent probes.

Self-assembly has been considered as a strategy to construct superstructures with specific functions, which has been widely used in many different fields, such as bionics, catalysis, and pharmacology. A detailed and in-depth analysis of the self-assembly mechanism is beneficial for directionally and accurately regulating the self-assembly process of substances. Fluorescent probes exhibit unique advantages of sensitivity, non-destructiveness, and real-time self-assembly tracking, compared with traditional methods. In this work, the design principle of fluorescent probes with different functions and their applications for the detection of thermodynamic and kinetic parameters during the self-assembly process were systematically reviewed. Their efficiency, limitations and advantages are also discussed. Furthermore, the promising perspectives of fluorescent probes for investigating the self-assembly process are also discussed and suggested.

Crystal Plane Engineering to Boost Water Cluster Evaporation for Enhanced Solar Steam Generation.

Polymer based low evaporation enthalpy materials have become a universal selection for improving the efficiency of solar steam generation. Although water cluster and intermediate water mechanisms have been proposed to explain the low evaporation enthalpy, the production process and microstructure of activated water are still unclear. Here, crystal plane engineering is used to investigate the intermediate water state and the water cluster activation mechanism. The unique open-closed coordination structure on the optimized crystal surface promotes the generation of firm water clusters by optimizing the intermediate water state. Under the similar solar energy absorption of all materials, crystal plane engineering increased the solar steam generation rate of the evaporator by 31.2% and increased the energy efficiency to 94.8%. Exploring the micro-evaporation process and activated water structure is expected to stimulate the development of the next generation low evaporation enthalpy materials.

Novel Pharmaceutical Cocrystals of Tegafur: Synthesis, Performance, and Theoretical Studies.

PURPOSE: Tegafur (TF) is one of the most important clinical antitumor drugs with poor water solubility, severely reducing its bioavailability. This work develops new cocrystals to improve the solubility of TF and systematically investigates the intermolecular interactions to provide new insights into the formation of cocrystal and changes in physicochemical properties. METHOD: In this paper, two new 1:1 cocrystals of TF with 2,4 dihydroxybenzoic acid (2,4HBA) and p-nitrophenol (PNP) were synthesized. The cocrystal products were identified and characterized by various solid state analysis techniques. And the high performance liquid chromatography (HPLC) was conducted to determine the solubility and dissolution rate of TF and cocrystals. Moreover, the quantum chemistry calculations of crystal structure provided theoretical support for the results. RESULT: Compared with pure TF, the solubility and dissolution rate of TF-2,4HBA is significantly increased in a pH 6.8 buffer at 37°C. Under accelerated storage conditions (40°C, 75% RH), all cocrystal exhibits excellent stability over 8 weeks. Hirshfeld surface (HS) analysis, atoms in molecules (AIM) analysis, interaction region indicator (IRI) analysis, molecular electrostatic potential surface (MEPS) analysis and frontier molecular orbital (HOMO-LUMO) analysis were integrated to understand the hydrogen bonding interaction more comprehensively. The simulation results are in good agreement with the experimental data. The results show that the analysis of physical and chemical properties of TF-PNP cocrystal and TF crystal by quantum chemistry method is reliable at molecular level. CONCLUSION: These results are helpful to provide guiding methods in the cocrystal development and theoretical study of tegafur.

Hydration Mechanism and Its Effect on the Solubility of Aripiprazole.

PROPOSE: The propose is to investigate the reasons for the insolubility of Form III in water and to explore the mechanism of the hydration process of Form III. METHODS: The conformational and cohesive energies of Form III and Form H1 were calculated using Gaussian 16 and Crystal Explorer 17. Gaussian 16 and Multiwfn 3.8 was used to calculate the molecular surface electrostatic potential of Form III and Form H1 and to calculate the energies of the stronger intermolecular interactions in the crystal structure. The behaviors of Form III in water were simulated using Gromacs 2020.6. Finally, the hydration process from Form III to Form H1 was monitored in situ using Raman spectroscopy. RESULTS: The conformational energies of Form III and H1 are almost the same. The cohesion energy of Form H1 is much larger than that of Form III because both number of hydrogen bonds and van der Waals interactions are higher in the Form H1. During the simulation, the supercell of APZ form a supramolecular cluster. Several molecules manually dismantled from the cluster spontaneously combine to form new molecular clusters. Both increases in temperature and external energy input accelerate the hydration process. CONCLUSIONS: More hydrogen bonds and strong van der Waals interactions in Form H1 lead to a greater stability. The overall decrease in polarity and the strong binding effect on APZ molecule clusters due to intermolecular interactions lead to the water insolubility of Form III. The hydration process from Form III to Form H1 follows a novel, dandelion sowing-like hydration mechanism.

Photoactuators Based on Plastically Flexible α-Cyanostilbene Molecular Crystals Driven by the Solid-State [2+2] Cycloaddition Reaction.

Organic photomechanical molecular crystals are promising candidates for photoactuators, which have potential applications as smart materials in various fields. However, it is still challenging to fabricate photomechanical molecular crystals with flexibility because most of the molecular crystals are brittle and the mechanism of flexible crystals remains controversial. Here, a plastically flexible α-cyanostilbene crystal has been synthesized that can undergo solid-state [2+2] cycloaddition reaction under violet or UV irradiation and exhibits excellent photomechanical bending properties. A hook-shaped crystal can lift 0.7 mg object upward by 1.5 cm, which proves its potential for application as photoactuators. When complex with the agarose polymer, the molecules will be in the form of macroscopic crystals, which can drive the composite films to exhibit excellent photomechanical bending performance. Upon irradiation with UV light, the composite film can quickly lift 18.0 mg object upward by 0.3 cm. The results of this work may facilitate the application of macroscale crystals as photoactuators.

Strategies for chiral separation: from racemate to enantiomer.

Chiral separation has become a crucial topic for effectively utilizing superfluous racemates synthesized by chemical means and satisfying the growing requirements for producing enantiopure chiral compounds. However, the remarkably close physical and chemical properties of enantiomers present significant obstacles, making it necessary to develop novel enantioseparation methods. This review comprehensively summaries the latest developments in the main enantioseparation methods, including preparative-scale chromatography, enantioselective liquid-liquid extraction, crystallization-based methods for chiral separation, deracemization process coupling racemization and crystallization, porous material method and membrane resolution method, focusing on significant cases involving crystallization, deracemization and membranes. Notably, potential trends and future directions are suggested based on the state-of-art "coupling" strategy, which may greatly reinvigorate the existing individual methods and facilitate the emergence of cross-cutting ideas among researchers from different enantioseparation domains.

Electro-intensified simultaneous decontamination of coexisting pollutants in wastewater.

The treatment of wastewater has become increasingly challenging as a result of its growing complexity. To achieve synergistic removal of coexisting pollutants in wastewater, one promising approach involves the integration of electric fields. We conducted a comprehensive literature review to explore the potential of integrating electric fields and developing efficient electro-intensified simultaneous decontamination systems for wastewater containing coexisting pollutants. The review focused on comprehending the applications and mechanisms of these systems, with a particular emphasis on the deliberate utilization of positive and negative charges. After analyzing the advantages, disadvantages, and application efficacy of these systems, we observed electro-intensified systems exhibit flexible potential through their rational combination, allowing for an expanded range of applications in addressing simultaneous decontamination challenges. Unlike the reviews focusing on single elimination, this work aims to provide guidance in addressing the environmental problems resulting from the coexistence of hazardous contaminants.

In-situ synthesized 2D MXene/TiO2/Fe hybrid with (001)-(101) surface heterojunction for degradation of tetracycline under visible light.

Tetracycline (TC) as a common antibiotic has adverse effects on human healthy and biological survival. In this study, a novel MXene/TiO2/Fe hybrid was designed and successfully synthesized by combination method of calcination and hydrothermal reduction. The photocatalysts were characterized by PXRD, SEM, TEM, VSM and XPS, etc. It was found that MXene/TiO2/Fe exhibited 2D multilayer structure like MXene. The in-situ synthesized TiO2 through calcinating MXene exhibited an octahedral biconical structure with exposed (001) and (101) facets. Surface heterojunction of (001) and (101) facets was formed within TiO2, which enhanced the separation of photogenerated electrons and holes. The residual MXene could play a role in co-catalyst to capture the photo-generated electrons from TiO2. Moreover, Fe nanoparticles not only optimize the band gap structure and increase the specific surface area, but also store the electrons as a good electrons acceptor, which further promote the separation of electrons and holes. The TC removal efficiency of optimal MXene/TiO2/Fe could reach 92% within 120 min. Moreover, the influence of external environment factors such as pH, catalyst dosages and common anions were investigated in detail. Mechanism analysis show that h+, •OH and •O2- are the main active substances. Finally, the degradation pathways were proposed according to LC-MS.

Polymorphism of Pradofloxacin: Crystal Structure Analysis, Stability Study, and Phase Transformation Behavior.

PURPOSE: Pradofloxacin is an important antibiotic with poor physical stability. At present, there is no systematic study on its polymorphic form. The purpose of this study is to develop new crystal forms to improve the stability of Pradofloxacin and systematically study the crystal transformation relationships to guide industrial production. METHOD: In this work, three solvent-free forms (Form A, Form B and Form C), a new dimethyl sulfoxide solvate (Form PL-DMSO) and a new hydrate (Form PL-H) were successfully obtained and the single crystal data of Form A, Form B and Form PL-DMSO were solved for the first time. Various solid state analysis techniques and slurry experiments have been used to evaluate the stability and determine phase transformation relationships of five crystal forms, the analysis of crystal structure provided theoretical support for the results. RESULT: The water vapor adsorption and desorption experiences of Forms A, B, C and Form PL-H were studied, and the results show that the new hydrate has good hygroscopic stability and certain development potential. The thermal stability of different forms was determined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) and the crystal structure shows that there are more hydrogen bonds and C - H···π interactions in form B, which is the reason why Form B is more stable than form A. Finally, the phase transformation relationships of the five crystal forms were systematically studied and discussed. CONCLUSION: These results are helpful to provide guiding methods in the production and storage of pradofloxacin.

Molecular Assembly and Nucleation Kinetics during Nucleation of 3,5-Dinitrobenzoic Acid.

As one of the most important processes in the process of crystallization, nucleation determines the physicochemical properties of the crystal products. The mechanism of nucleation has not been sufficiently understood due to the complexity of the molecular assembly process. In this work, a rigid molecule of 3,5-dinitrobenzoic acid (DNBA) was selected as the model compound to investigate the connection between nucleation kinetics and solution chemistry and to investigate the mechanism of nucleation. The nucleation induction period was determined by the nonrandom method, and the parameters including interfacial energy γ and collision frequency f0C0 were calculated. FTIR, NMR, and MS were used to analyze the existing form of DNBA molecules in solutions. It was found that the solute exists in the form of monomer, multimers, and solvates in different solvents. Besides, molecular simulation and calculation were also used to investigate the intermolecular interactions of DNBA in different solvents, and the relationship between the molecular existing form and the nucleation kinetics was revealed. Finally, a possible nucleation mechanism of DNBA molecules in solution was proposed.

Manipulation of Morphology, Particle Size of Barium Sulfate and the Interacting Mechanism of Methyl Glycine Diacetic Acid.

In this paper, methyl glycine diacetic acid (MGDA) was found to have great influence on the morphology and particle size of barium sulfate. The effects of additive, concentration, value of pH and reaction temperature on the morphology and particle size of barium sulfate were studied in detail. The results show that the concentration of reactant and temperature have little effect on the particle size of barium sulfate. However, the pH conditions of the solution and the dosage of MGDA can apparently affect the particle size distribution of barium sulfate. The particle size of barium sulfate particles increases and the morphology changes from polyhedral to rice-shaped with the decreasing of the dosage of MGDA. In solution with higher pH, smaller and rice-shaped barium sulfate was obtained. To investigate the interacting mechanism of MGDA, the binding energy between MGDA and barium sulfate surface was calculated. It was found that the larger absolute value of the binding energy would result in stronger growth inhibition on the crystal face. Finally, the experimental data and theoretical calculations were combined to elucidate the interacting mechanism of the additive on the morphology and particle size of barium sulfate.

Organic Crystals with Response to Multiple Stimuli: Mechanical Bending, Acid-Induced Bending and Heating-Induced Jumping.

Multiple stimuli-responsive molecular crystals are attracting extensive attentions due to their potential as smart materials, such as molecular machines, actuators, and sensors. However, the task of giving a single crystal multiple stimuli-responsive properties remains extremely challenging. Herein, we found two polymorphs (Form O and Form R) of a Schiff base compound, which could respond to multiple stimuli (external force, acid, heat). Form O and Form R have different elastic deformability, which can be attributed to the differences in the molecular conformation, structural packing and intermolecular interactions. Moreover, both polymorphs exhibit reversible bending driven by volatile acid vapor, which we hypothesize is caused by reversible protonation reaction of imines with formic acid. In addition, jumping can be triggered by heating due to the significant anisotropic expansion. The integration of reversible bending and jumping into one single crystal expands the application scope of stimuli-responsive crystalline materials.

Spatiotemporal control of l-phenyl-alanine crystallization in microemulsion: the role of water in mediating molecular self-assembly.

Water confined or constrained in a cellular environment can exhibit a diverse structural and dynamical role and hence will affect the self-assembly behavior of biomolecules. Herein, the role of water in the formation of l-phenyl-alanine crystals and amyloid fibrils was investigated. A microemulsion biomimetic system with controllable water pool size was employed to provide a microenvironment with different types of water, which was characterized by small-angle X-ray scattering, attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry. In a bound water environment, only plate-like l-phenyl-alanine crystals and their aggregates were formed, all of which are anhydrous crystal form I. However, when free water dominated, amyloid fibrils were observed. Free water not only stabilizes new oligomers in the initial nucleation stage but also forms bridged hydrogen bonds to induce vertical stacking to form a fibrous structure. The conformational changes of l-phenyl-alanine in different environments were detected by NMR. Different types of water trigger different nucleation and growth pathways, providing a new perspective for understanding molecular self-assembly in nanoconfinement.

Formation and stabilization mechanism of mesoscale clusters in solution.

To understand the existence of complex meso-sized solute-rich clusters, which challenge the understanding of phases and phase equilibria, the formation and stabilization mechanisms of clusters in solution during nucleation of crystals and the associated physico-chemical rules are studied in detail. An essential part of the mechanism is the formation of long-lived oligomers between solute molecules. By means of density functional theory simulation and nuclear magnetic resonance experiments, this work showed that the oligomers in solution tend to be π-π stacking dimers. Clusters are formed under the combined effect of diffusion and monomer-dimer reaction. The physically meaningful quantities such as the monomer-dimer reaction rate constants and the diffusion coefficients of both species were obtained by reaction-diffusion kinetics and diffusion-ordered spectroscopy results. The evolution of cluster radius as a function of time, and the qualitative spatial distributions of monomer and dimer densities under steady-state were plotted to better understand the formation process and the nature of the clusters.

Revealing the Molecular Mechanism of Cosolvency Based on Thermodynamic Phase Diagram, Molecular Simulation, and Spectrum Analysis: The Tolbutamide Case.

Cosolvency has been observed in many systems. To reveal the mechanism of cosolvency from the molecular level, the effects of molecular conformation, supramolecular clusters, and interactions on cosolvency were systematically investigated using tolbutamide as a model compound, through experimental exploration, spectral detection, and molecular simulation. The results show that, under the influence of intermolecular and intramolecular interactions, the dominant solute molecular conformations transform and the supramolecular clusters change in different solution systems, which then lead to the cosolvency phenomena.

ZIF-8 engineered bismuth nanosheet arrays for boosted electrochemical reduction of nitrate.

Removal of nitrate in wastewater is of great importance to environmental protection and humanity. However, the competitive reaction of hydrogen evolution (HER), which could occupy most active sites of the electrocatalyst, is one of the big challenges for nitrate removal. In this study, a novel zeolitic imidazolate framework-8 film engineered bismuth nanosheet electrocatalyst (ZIF-8/Bi-CC) was designed and synthesized for the electrochemical reduction of nitrate. The water contact angle and electrochemical tests demonstrated that the construction of the hydrophobic ZIF-8 film effectively weakened the competition of HER. And the nitrate removal efficiency and ammonium selectivity increased by 25.9% and 34.2% respectively after bismuth nanosheets were embedded into the ZIF-8 film. Besides, the bismuth concentration detection results indicated that the ZIF-8 film as the protective shell could effectively prevent the leaching of bismuth into the solution. More importantly, the final nitrate removal rate of ZIF-8/Bi-CC was close to 90% after 5 h when treating actual garbage fly ash wastewater, the NITRR efficiency stability and the obtained product were confirmed by five electrochemical cycles. The metal-organic framework film engineered electrocatalyst is a promising strategy for designing a new catalyst for the removal of nitrate in industrial wastewater.

Simultaneous decontamination of multi-pollutants: A promising approach for water remediation.

Water remediation techniques have been extensively investigated due to the increasing threats of soluble pollutants posed on the human health, ecology and sustainability. Confronted with the complex composition matrix of wastewater, the simultaneous elimination of coexisting multi-pollutants remains a great challenge due to their different physicochemical properties. By integrating multi-contaminants elimination processes into one unit operation, simultaneous decontamination attracted more and more attention under the consideration of versatile applications and economical benefits. In this review, the state-of-art simultaneous decontamination methods were systematically summarized as chemical precipitation, adsorption, photocatalysis, oxidation-reduction, biological removal and membrane filtration. Their applications, mechanisms, mutual interactions, sustainability and recyclability were outlined and discussed in detail. Finally, the prospects and opportunities for future research were proposed for further development of simultaneous decontamination. This work could provide guidelines for the design and fabrication of well-organized simultaneous decontaminating system.