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 ...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.展开更多
The pseudo-ternary system(Na Cl + Na_2SO_4+ H_2O) of coal gasification wastewater was studied at T =(268.15 to 373.15) K. The solubility and density of the equilibrium liquid phase were determined by the isothermal so...The pseudo-ternary system(Na Cl + Na_2SO_4+ H_2O) of coal gasification wastewater was studied at T =(268.15 to 373.15) K. The solubility and density of the equilibrium liquid phase were determined by the isothermal solution saturation method. The equilibrium solids were also investigated by the Schreinemaker's method of wet residues and X-ray powder diffraction(XRD). According to the experimental data, the phase diagrams were determined. It was found that there was no significant solubility difference on the Na Cl-rich side between the ternary system(Na Cl + Na_2SO_4+ H_2O) in coal gasification wastewater and in pure water. However, the solubility on the Na_2SO_4-rich side of coal gasification wastewater was apparently higher than that of pure water. The increase in the solubility of Na_2SO_4 was most likely caused by the effects of other impurities apart from Na Cl and Na_2SO_4 in coal gasification wastewater. The measured data and phase equilibrium diagrams can provide fundamental basis for salt recovery in coal gasification wastewater.展开更多
Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for ...Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for four weeks to induce hyperlipidemia,then 16S rRNA sequencing was used to compare the intestinal flora between hyperlipidemic and control diet-fed rats.Results:The microbiome of rats fed an HFD for four weeks differed from that of control diet-fed rats.Bacterial species that were less abundant were most affected by HFD feeding,among which were many pathogenic species,which became significantly more abundant.Eighteen genera were present in significantly different numbers in hyperlipidemic and control rats,more than half of which have been linked to infection and inflammation,or energy intake and obesity.The results indicated a type of stress response of the flora to a high-fat environment.In addition,the age of the rats tended to influence the gut microbial composition.Conclusion:These findings suggest that HFD may induce hyperlipidemia by affecting the gut microbial composition.Changes in the abundance of pro-inflammatory and pathogenic bacteria,and those that influence energy intake and obesity,may be important mediators of this.展开更多
In this paper, the gelation mechanism of erythromycin ethylsuccinate(EES) during crystallization is investigated for the first time. The generated semisolid gel-like phase exhibited a 3D fibrillar network morphology a...In this paper, the gelation mechanism of erythromycin ethylsuccinate(EES) during crystallization is investigated for the first time. The generated semisolid gel-like phase exhibited a 3D fibrillar network morphology and the typical rheological properties of gels. The fibers inside the gel-like phase were confirmed to be new types of EES solvates using powder X-ray diffraction, thermogravimetric analysis/differential scanning calorimetry, and gas chromatography. The gelation and crystallization regions in EES-1-propanol solid–liquid phase diagram were determined. Analyses of solvent parameters showed that moderate solvent polarity may promote EES gelation. Fourier transform infrared spectra, nuclear magnetic resonance spectra, and scanning electron microscopy analyses indicated that through intermolecular hydrogen bonds, EES and solvent molecules assembled into fibers via crystallographic mismatch branching growth. The fibers intertwined into a 3D network microstructure and formed a gel-like phase, completely immobilizing the solution.展开更多
Erythromycin thiocyanate is widely used for the production of other macrolide antibiotics. In this work, a novel heterosolvate of this pharmaceutical compound has been obtained and characterized for the first time, wh...Erythromycin thiocyanate is widely used for the production of other macrolide antibiotics. In this work, a novel heterosolvate of this pharmaceutical compound has been obtained and characterized for the first time, which was transformed from the dihydrate form in the acetone solvent through evaporation crystallization. Thermal behavior together with compositional analysis revealed that both water and acetone molecules participated in the formation of the crystal lattice which is rarely reported before. The general chemical name of the heterosolvate may be defined as erythromycin thiocyanate sesquihydrate hemiacetonate. Furthermore, studies on solid-state spectral analysis provided strong evidence of intermolecular hydrogen bonds in heterosolvate crystals. According to the crystal structure determined by single crystal X-ray diffraction, the formation mechanism of the heterosolvate is proposed in which strong multihydrogen bondings between water and solute molecules form the layer structure. While acetone molecules form single-hydrogen bonds with solutes and reside in channels between layers. This well explains why acetone solvent is easy to escape from the crystal structure during desolvation.展开更多
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 che...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.展开更多
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 bacteric...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.展开更多
Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells.Mitochondrial dynamics balance is exactly regulated by molecular motor consi...Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells.Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins.Thus,targeting myosin eactin molecular motor is considered as a promising strategy for anti-cancer.In this study,we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics via pharmacologically targeting molecular motor.Here,we found J13 could directly target myosin-9(MYH9)eactin molecular motor to promote mitochondrial fission progression,and markedly inhibited cancer cells survival,proliferation and migration.Mechanism study revealed that J13 impaired MYH9 eactin interaction to inactivate molecular motor,and caused a cytoskeleton-dependent mitochondrial dynamics imbalance.Moreover,stable isotope labeling with amino acids in cell culture(SILAC)technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9 eactin molecular motor to mitochondrial fission.Taken together,we reported the first natural small-molecule directly targeting MYH9 eactin molecular motor for anti-cancer translational research.Besides,our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.展开更多
Nucleation from solution is fundamental to many natural and industrial processes.The understanding of molecular mechanism of nucleation from solution is conducive to predict crystal structure,control polymorph and des...Nucleation from solution is fundamental to many natural and industrial processes.The understanding of molecular mechanism of nucleation from solution is conducive to predict crystal structure,control polymorph and design desired crystal materials.In this review,the nucleation theories,including classical nucleation theory(CNT),nonclassical nucleation theory,as well as other new proposed theories,were reprised,and the molecular mechanism of these theories was compared.Then,the molecular process of nucleation,including the current study techniques,the effect of molecular self-assembly in solutions,desolvation process,as well as the properties of solvent and crystal structure on nucleation from solution were summarized.Furthermore,the relationship of molecular conformation in solution and in crystal,and the effect of solute molecular flexibility on nucleation were discussed.Finally,the current challenges and future scopes of crystal nucleation from solution were discussed.展开更多
In this paper a porous media seepage model was applied to analyze the permeability and study the seepage process of crystal pillar formed in the preparation of electronic grade phosphoric acid(EGPA).By inspecting the ...In this paper a porous media seepage model was applied to analyze the permeability and study the seepage process of crystal pillar formed in the preparation of electronic grade phosphoric acid(EGPA).By inspecting the seeping process,the structure parameter of crystal pillar could be obtained.Two basic ideal models(perfectly separated model and perfectly connected model)were presented and a characterized factorφwas introduced to modify the model.A good simulation result was obtained which met the experiment result well.The relationship betweenφand permeability were also discussed.The characterized factorφshowed potential application on optimizing process.展开更多
6-Aminopenicillanic acid(6-APA)is a crucial pharmaceutical intermediate in the chemistry of semi-synthetic antibiotics.The focused beam reflectance measurement(FBRM)technology and particle vision measurement(PVM)techn...6-Aminopenicillanic acid(6-APA)is a crucial pharmaceutical intermediate in the chemistry of semi-synthetic antibiotics.The focused beam reflectance measurement(FBRM)technology and particle vision measurement(PVM)technology were employed to the processes of online-monitoring of 6-APA crystallization behavior in a double-feeding semi-batch crystallizer.Experiments were carried out with four kinds of double-feeding policies and the results were compared with the traditional single-feeding.Records and analysis of FBRM indicated that the nucleation of double feeding policy was much higher than single policy,and chord length of 6-APA was almost determined and had little change after the nucleation peak.Ostwald ripening process had no significant effect on further growth of 6-APA crystal.PVM images showed that the crystal habit of 6-APA was continuously changed during the crystallization process.The development of(002)face in the final crystal for the five feeding policies were different.展开更多
Penicillin sulfoxide is the intermediate for the synthesis of 7-amino-3-desacetoxycephalosporanic acid which is one of the most important nucleuses of cephalosporin antibiotic.In this contribution,two crystal structur...Penicillin sulfoxide is the intermediate for the synthesis of 7-amino-3-desacetoxycephalosporanic acid which is one of the most important nucleuses of cephalosporin antibiotic.In this contribution,two crystal structures of penicillin sulfoxide(forms I and II)were determined by X-ray diffraction,and their thermotropic properties were investigated by differential scanning calorimetry(DSC).Furthermore,the transformation of form II to form I was studied quantitatively by Raman spectroscopy,and its rates at different temperatures were determined.The results indicate that penicillin sulfoxide is more stable as form I,and the temperature plays an important role in the crystal transformation.展开更多
基金financially supported by the Innovative Group Project of China (21621004)Demonstration Project of Integration of Science, Education and Industry in Qilu University of Technology (2020KJC-ZD09)
文摘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.
基金Supported by the National Key Research and Development Program of China(2016YFB0600504)
文摘The pseudo-ternary system(Na Cl + Na_2SO_4+ H_2O) of coal gasification wastewater was studied at T =(268.15 to 373.15) K. The solubility and density of the equilibrium liquid phase were determined by the isothermal solution saturation method. The equilibrium solids were also investigated by the Schreinemaker's method of wet residues and X-ray powder diffraction(XRD). According to the experimental data, the phase diagrams were determined. It was found that there was no significant solubility difference on the Na Cl-rich side between the ternary system(Na Cl + Na_2SO_4+ H_2O) in coal gasification wastewater and in pure water. However, the solubility on the Na_2SO_4-rich side of coal gasification wastewater was apparently higher than that of pure water. The increase in the solubility of Na_2SO_4 was most likely caused by the effects of other impurities apart from Na Cl and Na_2SO_4 in coal gasification wastewater. The measured data and phase equilibrium diagrams can provide fundamental basis for salt recovery in coal gasification wastewater.
基金the National Natural Science Foundation of China(81773960 and 81973535)the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2017ZX09301011).
文摘Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for four weeks to induce hyperlipidemia,then 16S rRNA sequencing was used to compare the intestinal flora between hyperlipidemic and control diet-fed rats.Results:The microbiome of rats fed an HFD for four weeks differed from that of control diet-fed rats.Bacterial species that were less abundant were most affected by HFD feeding,among which were many pathogenic species,which became significantly more abundant.Eighteen genera were present in significantly different numbers in hyperlipidemic and control rats,more than half of which have been linked to infection and inflammation,or energy intake and obesity.The results indicated a type of stress response of the flora to a high-fat environment.In addition,the age of the rats tended to influence the gut microbial composition.Conclusion:These findings suggest that HFD may induce hyperlipidemia by affecting the gut microbial composition.Changes in the abundance of pro-inflammatory and pathogenic bacteria,and those that influence energy intake and obesity,may be important mediators of this.
基金supported by the National Natural Science Foundation of China(Nos.21576187,21776203)
文摘In this paper, the gelation mechanism of erythromycin ethylsuccinate(EES) during crystallization is investigated for the first time. The generated semisolid gel-like phase exhibited a 3D fibrillar network morphology and the typical rheological properties of gels. The fibers inside the gel-like phase were confirmed to be new types of EES solvates using powder X-ray diffraction, thermogravimetric analysis/differential scanning calorimetry, and gas chromatography. The gelation and crystallization regions in EES-1-propanol solid–liquid phase diagram were determined. Analyses of solvent parameters showed that moderate solvent polarity may promote EES gelation. Fourier transform infrared spectra, nuclear magnetic resonance spectra, and scanning electron microscopy analyses indicated that through intermolecular hydrogen bonds, EES and solvent molecules assembled into fibers via crystallographic mismatch branching growth. The fibers intertwined into a 3D network microstructure and formed a gel-like phase, completely immobilizing the solution.
基金The authors are grateful to the financial support of the National Natural Science Foundation of China （81361140344, 21676179, and 21376164）, the ＂863＂ Program （2015AA021002）, the Major Project of Tianjin （15JCZDJC33200）, the National Major Scientific Instrument Development Project （21527812）, and the National Major Science and Technology Program for Water Pollution Control and Treatment （2015ZX07202-13）.
文摘Erythromycin thiocyanate is widely used for the production of other macrolide antibiotics. In this work, a novel heterosolvate of this pharmaceutical compound has been obtained and characterized for the first time, which was transformed from the dihydrate form in the acetone solvent through evaporation crystallization. Thermal behavior together with compositional analysis revealed that both water and acetone molecules participated in the formation of the crystal lattice which is rarely reported before. The general chemical name of the heterosolvate may be defined as erythromycin thiocyanate sesquihydrate hemiacetonate. Furthermore, studies on solid-state spectral analysis provided strong evidence of intermolecular hydrogen bonds in heterosolvate crystals. According to the crystal structure determined by single crystal X-ray diffraction, the formation mechanism of the heterosolvate is proposed in which strong multihydrogen bondings between water and solute molecules form the layer structure. While acetone molecules form single-hydrogen bonds with solutes and reside in channels between layers. This well explains why acetone solvent is easy to escape from the crystal structure during desolvation.
基金supported by National Natural Science Foundation of China(2193000361).
文摘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.
基金supported by the National Natural Science Foundation of China(22108196 and 21978201)the National College Student Innovation and Entrepreneurship Training Program(202110056036)。
基金The authors are grateful to the financial support of the National Natural Science Foundation of China(grant No.22108195)Nature Science Foundation of Tianjin(grant No.21JCQNJC00580)+1 种基金Key R&D Program of Zhejiang(grant No.2022c01208)Haihe Laboratory of Sustainable Chemical Transformations,and the key project of State Key Laboratory of Chemical Engineering(grant No.SKL-ChE-20Z03).
文摘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.
基金supported by the National Key Technology R&D Program“New Drug Innovation”of China[Nos.2019YFC1711000 and 2019YFC1708902]the National Natural Science Foundation of China[Nos.81973505 and 81773932]
文摘Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells.Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins.Thus,targeting myosin eactin molecular motor is considered as a promising strategy for anti-cancer.In this study,we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics via pharmacologically targeting molecular motor.Here,we found J13 could directly target myosin-9(MYH9)eactin molecular motor to promote mitochondrial fission progression,and markedly inhibited cancer cells survival,proliferation and migration.Mechanism study revealed that J13 impaired MYH9 eactin interaction to inactivate molecular motor,and caused a cytoskeleton-dependent mitochondrial dynamics imbalance.Moreover,stable isotope labeling with amino acids in cell culture(SILAC)technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9 eactin molecular motor to mitochondrial fission.Taken together,we reported the first natural small-molecule directly targeting MYH9 eactin molecular motor for anti-cancer translational research.Besides,our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.
基金This research was financially supported by the National Natural Science Foundation of China （No. 21376165）, the Key Project of Tianjin Science and Technology Support Program （No. 13ZCZDNC08900） and the Tianjin Municipal Natural Science Foundation （No. 13JCZDJC28400）.
文摘cefquinome 硫酸盐的稳固液体的平衡数据是重要的为 cefquinome 硫酸盐开发工业结晶化过程。在从 277.15 ～ 305.15 K 的五纯溶剂(甲醇，乙醇，乙烯乙二醇，醋酸和水) 并且在从 278.15 ～ 293.15 K 的二进制丙酮水溶剂的 cefquinome 硫酸盐的溶解度在气压被测量。而混合溶剂系统数据被相关到修改 Apelblat， Vant Hoff， CNIBS/R-K 和 Jouyban- Acree 模型，纯溶剂的溶解度数据被相关到修改 Apelblat 和 Vant Hoff 方程。在所有测试溶剂的 cefquinome 硫酸盐的溶解度与增加温度减少了，这被发现。另外，包括免费精力，热含量和熵改变的标准吉布斯，溶解过程的热力学的性质用 Vant Hoff 方程被计算。cefquinome 硫酸盐的溶解是发热的，这被发现。
基金supported by the National Natural Science Foundation of China(21978201)。
文摘Nucleation from solution is fundamental to many natural and industrial processes.The understanding of molecular mechanism of nucleation from solution is conducive to predict crystal structure,control polymorph and design desired crystal materials.In this review,the nucleation theories,including classical nucleation theory(CNT),nonclassical nucleation theory,as well as other new proposed theories,were reprised,and the molecular mechanism of these theories was compared.Then,the molecular process of nucleation,including the current study techniques,the effect of molecular self-assembly in solutions,desolvation process,as well as the properties of solvent and crystal structure on nucleation from solution were summarized.Furthermore,the relationship of molecular conformation in solution and in crystal,and the effect of solute molecular flexibility on nucleation were discussed.Finally,the current challenges and future scopes of crystal nucleation from solution were discussed.
文摘In this paper a porous media seepage model was applied to analyze the permeability and study the seepage process of crystal pillar formed in the preparation of electronic grade phosphoric acid(EGPA).By inspecting the seeping process,the structure parameter of crystal pillar could be obtained.Two basic ideal models(perfectly separated model and perfectly connected model)were presented and a characterized factorφwas introduced to modify the model.A good simulation result was obtained which met the experiment result well.The relationship betweenφand permeability were also discussed.The characterized factorφshowed potential application on optimizing process.
文摘6-Aminopenicillanic acid(6-APA)is a crucial pharmaceutical intermediate in the chemistry of semi-synthetic antibiotics.The focused beam reflectance measurement(FBRM)technology and particle vision measurement(PVM)technology were employed to the processes of online-monitoring of 6-APA crystallization behavior in a double-feeding semi-batch crystallizer.Experiments were carried out with four kinds of double-feeding policies and the results were compared with the traditional single-feeding.Records and analysis of FBRM indicated that the nucleation of double feeding policy was much higher than single policy,and chord length of 6-APA was almost determined and had little change after the nucleation peak.Ostwald ripening process had no significant effect on further growth of 6-APA crystal.PVM images showed that the crystal habit of 6-APA was continuously changed during the crystallization process.The development of(002)face in the final crystal for the five feeding policies were different.
基金grateful to North China Pharmaceutical Group Corporation Beta Co,.Ltd.for supplying penicillin sulfoxide.
文摘Penicillin sulfoxide is the intermediate for the synthesis of 7-amino-3-desacetoxycephalosporanic acid which is one of the most important nucleuses of cephalosporin antibiotic.In this contribution,two crystal structures of penicillin sulfoxide(forms I and II)were determined by X-ray diffraction,and their thermotropic properties were investigated by differential scanning calorimetry(DSC).Furthermore,the transformation of form II to form I was studied quantitatively by Raman spectroscopy,and its rates at different temperatures were determined.The results indicate that penicillin sulfoxide is more stable as form I,and the temperature plays an important role in the crystal transformation.
