Dissolution behavior,thermodynamic and kinetic analysis of malonamide by experimental measurement and molecular simulation

In this study,the solid structure,dissolution behavior,thermodynamic properties and nucleation kinetics of malonamide were explored.Firstly,the Hirshfeld surface analysis and molecular electrostatic potential surface were plotted to reveal the percentage contribution of various intermolecular contacts and location of the strongest hydrogen bond.Next,the solubility of malonamide in 12 solvents was determined by dynamic method at temperatures from 278.15 K to 318.15 K.Four thermodynamic models were applied to analyze solubility results.In addition,the thermodynamic properties were calculated to further analyze and discuss the dissolution behavior of malonamide.Moreover,the physicochemical properties of solvents were explored to express the solvent effects.The results illustrate“like dissolves like”,“mass transfer”and“solvent–solute interaction”rules play the synergistic effects on the dissolution process.The molecular dynamic simulation,including radial distribution function analysis and solvent free energy,was used to further explain the dissolution behavior.At last,the nucleation rate and effective interfacial energy in methanol solvent was measured and calculated to reveal the nucleation behaviour.

Amorphous and humidity caking: A review

Caking of products is a common and undesired phenomenon in food, chemical, pharmaceutical, and fertilizer industries which leads to extra cost and irregular quality. In general, caking processes could be identified as amorphous caking or humidity caking. In this review, history of studying caking, formation, methods, and prospects of these two caking processes are summarized and discussed. The relevant studies from the 1920 s to today are mentioned briefly. According to the different properties(i.e. hygrocapacity, hygrosensitivity, mechanical properties, and diffusion behavior) of amorphous powders and crystals, the conditions and mechanisms of amorphous and humidity caking are discussed. It is summarized that glass transition, moisture sorption, quantitative methods characterizing caking, accelerated caking tests, and simulation of caking behaviors are the main aspects that should be studied for a caking process. The methods for these five aspects are reviewed. Potential research points are proposed including caking of mixed particles, caking with phase transition or polymorph transition,non-homogenous caking, and simulation of caking.

Strategies for enhancing peroxymonosulfate activation by heterogenous metal-based catalysis:A review

Sulfate radical-advanced oxidation processes(SR-AOPs)are promising technologies for organic pollutants elimination.Heterogeneous metal-based catalysis has been widely studied and applied to activate peroxymonosulfate(PMS)for producing sulfate radicals.Developing highly efficient catalysts is crucial for future extensive use.Importantly,the catalytic activity is mainly determined by mass and electron transfer.This paper aims to overview the recent enhancement strategies for developing heterogeneous metalbased catalysts as effective PMS activators.The main strategies,including surface engineering,structural engineering,electronic modulation,external energy assistance,and membrane filtration enhancement,are summarized.The potential mechanisms for improving catalytic activity are also introduced.Finally,the challenges and future research prospects of heterogenous metal-based catalysis in SR-AOPs are proposed.This work is hoped to guide the rational design of highly efficient heterogenous catalysts in SR-AOPs.

Ultrasound assisted crystallization of cephalexin monohydrate:Nucleation mechanism and crystal habit control

With the high-quality requirements for cephalexin monohydrate,developing a robust and practical crystallization process to produce cephalexin monohydrate with good crystal habit,appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed.This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control.The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time.Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate.Furthermore,on the basis of classical nucleation theory and induction time data,a series of nucleation-related parameters(such as crystalliquid interfacial tension,radius of the critical nucleus and etc.)were calculated and showed a decreasing trend under ultrasound irradiation.The diffusion coefficient of the studied system was also determined to increase by 72.73%under ultrasound.The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process.In further,the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work.Through the exploration of crystallization conditions,it is found that suitable ultrasonic treatment,seeding,supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product.Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

Insight into the degradation mechanism of cefixime under crystallization condition

The chemical stability of cefixime was determined by high-performance liquid chromatography(HPLC) under different conditions, including factors such as p H, solvents, initial concentration, temperature and additives.The degradation process follows the first-order kinetics. A p H-rate profile exhibits the U-shape and shows the maximum stability of cefixime at pH = 6. The stability in different pure solvents is ranked as acetone N ethanol N methanol N water, while the degradation rate of cefixime exists a maximum at the ratio of 0.6 in water + methanol mixtures. In addition, the degradation rate increases with the temperature increasing and the activation energy of degradation was found to be 27.078 k J·mol^(-1) in acetone + water mixed solvents. The addition of different additives was proven to either inhibit or accelerate the degradation. The degradation products were analyzed using HPLC, LC–MS and infrared spectroscopy, and the possible degradation pathways in acid as well as alkaline environment were proposed to help us understand the degradation behavior of cefixime.

Research progress on preparation and purification of fluorine-containing chemicals in lithium-ion batteries

With the development of digital products,electric vehicles and energy storage technology,electronic chemicals play an increasingly prominent role in the field of new energy such as lithium-ion batteries.Electronic chemicals have attracted extensive attention in various fields.Characteristics of high-end electronic chemicals are high purity and low impurity content,which requires a very strict separation and purification process.At present,crystallization is a key technology for their separation and purification of electronic chemicals.In this work,the representative fluorine-containing compounds in cathode and anode materials,separator and electrolyte of lithium-ion batteries are introduced.The latest technologies for the preparation and purification of four kinds of fluorine-containing battery chemicals by crystallization technology are reviewed.In addition,the research prospects and suggestions are put forward for the separation of fluorine-containing battery chemicals.

Flexible Organic Crystal with Two-Dimensional Elastic Bending and Recoverable Plastic Twisting for Circularly Polarized Luminescence

Multidimensional mechanical flexible organic crystals with tunable optoelectronic properties hold significant promise for practical application in complicated environmental conditions.Herein,based on a newly designed“flexible”Schiff base small molecule with chirality,we presented a compatibly bendable and twistable organic single crystal with circularly polarized luminescence for the first time.First,the twodimensional elastic bending of the chiral crystal was realized at both room and liquid nitrogen temperatures,along with recoverable plastic twisting at room temperature.Besides,circular dichroism and circularly polarized luminescence spectroscopy were employed to characterize the chiral enantiomer in solution and the solid state.Our design strategy provides a new perspective for the future construction of chiroptical flexible crystal materials.

人体生物矿化与病态结晶研究进展

生物体通过矿化结晶可制备出具有多层级结构有序的功能材料以实现特定生物功能,但是有害(或病态)的结晶过程则会诱发诸如肾结石、动脉粥样硬化、疟疾、痛风等疾病.迄今为止,科学家对哺乳动物体内无机或有机盐病态矿化结晶的分子机制认识仍不清楚,但随着结晶科学推动病态矿化领域的发展,生物病态结晶研究近年来已取得了众多突破性成果和重要进展.本文从结晶过程机理认识和抑制药物分子开发需求出发,首先介绍了病态矿化结晶过程诱发的几种常见人类疾病,综述了这些疾病相关的无机或有机盐晶体结晶过程机制的研究进展,重点阐述了诱发肾结石形成的晶体成核、生长、聚结和黏附不同阶段、不同尺度的分子机制研究进展以及结晶抑制药物分子的设计开发策略.最后,梳理了今后生物病态结晶领域研究的重点方向,为病态矿化引发的人类疾病的预防、治疗和药物研究开发提供指导.

高效四端钙钛矿/铜铟镓硒叠层太阳能电池

随着能源需求的不断增长和化石能源的日益枯竭,清洁能源的发展正在受到越来越多的重视.其中,太阳能电池可将太阳光能转化为电能,作为一种高效、可靠、环保的清洁能源利用技术,将在未来的能源体系中扮演重要角色.近年来铅基卤化物杂化钙钛矿太阳能电池因同时具有高光电转换效率和潜在的低制造成本,迅速成为太阳能科学的前沿热点领域.单结钙钛矿电池的能量转化效率的世界纪录目前已达26.0%.

A new strategy to design isostructural salts: The case of the antitumor drug dimethylaminomicheliolide

Isostructural multicomponent crystals provide a promising way for fine-tuning physicochemical properties, whereas their design remains quite challenging. The purpose of this work was to provide a new strategy for obtaining isostructural multicomponent crystals by introducing coformers with functional group positional isomerism. Five isostructural salts of an antitumor drug dimethylaminomicheliolide(DMAMCL) were reported and designed with a series of dihydroxybenzoic acid regioisomers for the first time, which were identified by power and single-crystal X-ray diffractions. Similar lattice parameters suggested these obtained salts may have the same crystal packing mode. The quantitative similarity parameters via XPac, Crystal CMP and Mercury program further proved these crystal structures are3D isostructural. Hirshfeld surface maps and 2D fingerprint plots show that the isostructural salts have similar intermolecular interactions. Compared with DMAMCL, obvious improvement was observed in the thermal stability, hygroscopicity, and solubility of these isostructural salts. Meanwhile, isostructural crystals may have different physicochemical properties, even though the shape and molecular size are similar and the packing of crystal structures is equally matched.

Exploring the influence of crystal packing on the optical-physical property of quercetin-based binary and ternary solid forms

The co-crystallization of quercetin(Qur)with a flexible molecule 4-(4-pyridinyldisulfanyl)pyridine(DPDS)in different solvents and conditions was investigated,yielded five multi-component crystalline phases and characterized with X-ray diffractions and thermal analysis.Although the crystal system of Qur-DPDSMe OH and Qur-DPDS-Dioxane is the same,the desolvation results revealed that Qur-DPDS-Me OH transformed to Qur-DPDS when Me OH solvent molecules escape from the lattice,while Qur-DPDS-Dioxane transformed to Qur-DPDS-II through a similar process,which is same with Qur-DPDS-THF.These two cocrystal polymorphs Qur-DPDS and Qur-DPDS-II obey an enantiotropic relationship.Moreover,the formation of cocrystal solvates improves the packing efficiency of crystals.Crystal structure analysis showed that hydrogen bonds and conformations of the corresponding parent molecules play a major role in molecular assembly and crystal packing patterns,thus bring different physicochemical properties.Finally,the fluorescence spectra and quantum-chemical calculations were carried out to explore the difference in the optical-physical properties.

Design spherical particles of potassium peroxymonosulfate compound salt with high stability and good powder properties via an agglomeration-dissolution mechanism

With the outbreak of COVID-19,disinfection protection has become a necessary measure to prevent infection.As a new type of disinfectant,potassium peroxymonosulfate compound salt(PMS)has the advantages of good bactericidal effect,non-toxicity,high safety and stability.However,the current PMS products with irregular particle shapes lead to poor flowability,high hygroscopicity,poor stability of reactive oxygen species(ROS)and serious caking problems.In this work,an agglomeration-dissolution mechanism was designed to prepare spherical PMS particles with large size(>300μm)and high sphericity(up to 90%),effectively addressing the above problems.Shaping(dissolution and abrasion)is the key to improving sphericity,which is mainly controlled by the design of the heating mode,residence time and stirring rate.Compared with the irregular PMS particles,the large spherical particles present better flowability(angle of repose decreased by 35.80%,Carr's index decreased by 64.29%,Hausner's ratio decreased by 19.14%),lower hygroscopicity(decreased by 38.0%),lower caking ratio(decreased by 84.50%),and higher stability(the monthly loss of ROS was reduced by 61.68%).The agglomeration-dissolution mechanism demonstrates the crystallization,agglomeration,dissolution and abrasion process of inorganic salt crystals,providing an opportunity to prepare high-end inorganic crystal materials with high-quality morphologies.

Tat-functionalized Ag-Fe_3O_4 nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery

In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide(Tat), producing Tat-modified Ag-Fe_3O_4 nanocomposites(Tat-FeAgNPs). To load drugs, an –SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin(Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed in vitro using MCF-7 cells, and in vivo using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles,with the IC_(50) of Tat-FeAgNP-Dox to be 0.63 mmol/L. The in vivo delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the in vivo optical imaging tests, in which TatFeAgNP-Cy5 yielded the most efficient accumulation in the tumor(6.772.4% ID of Tat-FeAgNPs).Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6%(P ? 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.

Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration.However,no systemic investigations have been made on the change of this pharmacokinetic difference,resulted either from the physiological or from the pathological factors.In this paper,we used polymorphic nimodipine(Nim) as a model drug and investigated the effect of age difference(2- and 9-month old) on the pharmacokinetics after oral delivery in rats.As the results shown,for L-form of Nim(L-Nim),the AUC0–24 hin 2-month-old rats was 343.68747.15 ng h/m L,which is 23.36% higher than that in 9-month-old rats.For H-form of Nim(H-Nim),the AUC0–24 hin 2-monthold rats was 140.91719.47 ng h/m L,which is 54.64% higher than that in 9-month-old rats.The AUC0–24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats.Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs,the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

Ultrasound-mediated targeted microbubbles： a new vehicle for cancer therapy

With the hope of overcoming the serious side effects, great endeavor has been made in tumor-targeted chemotherapy, and various drug delivery modalities and drug carriers have been made to decrease systemic toxicity caused by chemotherapeutic agents. Scientists from home and abroad focus on the research of targeted microbubbles contrast agent, and the use of the targeted ultrasound microbubble contrast agent can carry gene drugs and so on to the target tissue, as well as mediated tumor cell apoptosis and tumor microvascular thrombosis block, etc., thus plays the role of targeted therapy. Recent studies have elucidated the mechanisms of drug release and absorption, however, much work remains to be done in order to develop a successful and optimal system. In this review, we summarized the continuing efforts in under-standing the usage of the ultrasound triggered target microbubbles in cancer therapy, from release mechanism to preparation methods. The latest applications of ultra-sound-triggered targeted microbubbles in cancer therapy, especially in gene therapy and antiangiogenic cancer therapy were discussed. Moreover, we concluded that as a new technology, ultrasound-triggered targeted microbubbles used as drug carriers and imaging agents are still energetic and are very likely to be translated into clinic in the near future.

能带调控助力基于MnS空穴传输层的全无机高效稳定Sb_(2)(S,Se)_(3)太阳能电池

近年,锑硫化合物[Sb_(2)S_(x)Se_(3-0)<x<3)已迅速成为太阳能电池中的新型吸光材料研究热点.然而,高效(超过9%)的锑基太阳能电池通常是使用昂贵且稳定性差的有机空穴传输层(HTL,Spiro-OMeTAD).因此,开发成本低且稳定性好的新型无机HTL迫在眉睫.本文利用热蒸法制备MnS薄膜,并利用它作为HTL构建Sb_(2)(S,Se)_(3)太阳能电池。研究表明,在空气中低温退火有利于MnS与Sb_(2)(S,Se)_(3)形成更好的能带匹配从而实现空穴有效提取.基于此,作者制备得到迄今为止最高效率(9.24%)的全无机Sb_(2)(S,Se)_(3)太阳能电池.

Significance and strategies in developing delivery systems for bio-macromolecular drugs

Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system （DDS） is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug （e.g., protein toxins, gene products, etc.） is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent （e.g., doxorubicin）. Hence, bio-macromolecular drugs have been recognized around the world as the future ＂drug-of-choice＂. Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs （an exceedingly low 1.2%）, reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold： （1） the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and （2） the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.

Machine learning-based solubility prediction and methodology evaluation of active pharmaceutical ingredients in industrial crystallization

Solubility has been widely regarded as a fundamental property of small molecule drugs and drug candidates,as it has a profound impact on the crystallization process.Solubility prediction,as an alternative to experiments which can reduce waste and improve crystallization process efficiency,has attracted increasing attention.However,there are still many urgent challenges thus far.Herein we used seven descriptors based on understanding dissolution behavior to establish two solubility prediction models by machine learning algorithms.The solubility data of 120 active pharmaceutical ingredients(APIs)in ethanol were considered in the prediction models,which were constructed by random decision forests and artificial neural network with optimized data structure and model accuracy.Furthermore,a comparison with traditional prediction methods including the modified solubility equation and the quantitative structure-property relationships model was carried out.The highest accuracy shown by the testing set proves that the ML models have the best solubility prediction ability.Multiple linear regression and stepwise regression were used to further investigate the critical factor in determining solubility value.The results revealed that the API properties and the solute-solvent interaction both provide a nonnegligible contribution to the solubility value.