Experimental verification of nanonization enhanced solubility for poorly soluble optoelectronic molecules

Solubility enhancement has been a priority to overcome poor solubility with optoelectronic molecules for solution-processable devices. This study aims to obtain experimental data on the effect of particle sizes on the solubility properties of several typical optoelectronic molecules in organic solvents, including the solubility results of 1,3-bis(9-carbazolyl)benzene(m CP), 1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)ben zene(TPBi) and 2-(4-tert-butylphenyl)-5-(4-biphenyl)-1,3,4-oxadiazole(PBD) in ethanol and acetonitrile,respectively. Nanoparticles of m CP, TPBi and PBD with sizes from dozens to several hundred nanometers were prepared by solvent antisolvent precipitation method and their solubility were determined by using isothermal saturation method. The saturation solubility of nanoparticles of three kinds of optoelectronic molecules exhibited increase of 12.9%-25.7% in comparison to the same raw materials in the form of microparticles. The experimental evidence indicates that nanonization technology is a feasible way to make optoelectronic molecules dissolve in liquids with enhanced solubility.

Study of the Relationship Between New Ionic Interaction Parameters and Salt Solubility in Electrolyte Solutions Based on Molecular Dynamics Simulation

Studying the relationship between ionic interactions and salt solubility in seawater has implications for seawater desalination and mineral extraction.In this paper,a new method of expressing ion-to-ion interaction is proposed by using molecular dynamics simulation,and the relationship between ion-to-ion interaction and salt solubility in a simulated seawater water-salt system is investigated.By analyzing the variation of distance and contact time between ions in an electrolyte solution,from both spatial and temporal perspectives,new parameters were proposed to describe the interaction between ions:interaction distance(ID),and interaction time ratio(ITR).The best correlation between characteristic time ratio and solubility was found for a molar ratio of salt-to-water of 10:100 with a correlation coefficient of 0.96.For the same salt,a positive correlation was found between CTR and the molar ratio of salt and water.For type 1-1,type 2-1,type 1-2,and type 2-2 salts,the correlation coefficients between CTR and solubility were 0.93,0.96,0.92,and 0.98 for a salt-to-water molar ratio of 10:100,respectively.The solubility of multiple salts was predicted by simulations and compared with experimental values,yielding an average relative deviation of 12.4%.The new ion-interaction parameters offer significant advantages in describing strongly correlated and strongly hydrated electrolyte solutions.

Solubility of iron(Ⅲ) and nickel(Ⅱ) acetylacetonates in supercritical carbon dioxide

As a common precursor for supercritical CO_(2)(scCO_(2))deposition techniques,solubility data of organometallic complexes in scCO_(2)is crucial for the preparation of nanocomposites.Recently,metal acetylacetonates have shown great potential for the preparation of single-atom catalytic materials.In this study,the solubilities of iron(Ⅲ)acetylacetonate(Fe(acac)3)and nickel(Ⅱ)acetylacetonate(Ni(acac)2)were measured at the temperature from 313.15 to 333.15 K and in the pressure range of 9.5–25.2 MPa to accumulate new solubility data.Solubility was measured using a static weight loss method.The semi-empirical models proposed by Chrastil and Sung et al.were used to correlate the solubility data of Fe(acac)3 and Ni(acac)2.The equations obtained can be used to predict the solubility of the same system in the experimental range.

Preparation, characterization and evaluation of kaempferol phospholipid complex: Improvement of its solubility and biological eff ect

Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has been prepared by solvent evaporation for the enhancement of the bioavailability of KA.KA-PC was verified by scanning electron microscope characterization methods.Drug loading,solubility and long-term stability were measured.The characterization results showed that KA-PC was formed through the intermolecular interaction between KA and phospholipids.The solubility of KA-PC in water was 189 times higher than that of KA,and the solubility in n-octanol was also significantly improved.Besides,pharmacodynamic studies showed that KA-PC can significantly reduce the level of serum uric acid in mice without causing renal injury.This study expanded the clinical application of KA by preparing KA-PC.

Overview of milling techniques for improving the solubility of poorly water-soluble drugs

Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are especially desired in formulations designed for parenteral,respiratory and transdermal use.Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents,often to enhance processability or solubility especially for drugs with limited aqueous solubility.The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size,specific surface area and shape of the drug particles as well as millinginduced amorphization and/or structural disordering of the drug crystal(mechanochemical activation).Technology advancements in milling now enable the production of drug micro-and nano-particles on a commercial scale with relative ease.This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs.Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

Elementary osmotic pump(EOP)is a unique extended release(ER)drug delivery system based on the principle of osmosis.It has the ability to minimize the amount of the drug,accumulation and fluctuation in drug level during chronic uses.Carbamazepine(CBZ),a poorly water-soluble antiepileptic drug,has serious side effects on overdoses and chronic uses.The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance.Firstly,a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug.Then,designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance(ANOVA),respectively.The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone(PVP K30)and sodium lauryl sulfate(SLS).The plasticizer amount and molecular weight(MW)together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane(SPM)thickness inversely influence the release rate.In addition,the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core.Further,orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm.In this study we report the successful formulation of CBZ-EOP tablets,which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80%of CBZ at a rate of approximately zero order for up to 12 h.

STUDY ON THE MUTUAL SOLUBILITY OF WATER GLASS AND WATER SOLUBLE ORGANIC BINDER

The careful studies have been made into the mutual solubility of water glass and water soluble organic binder in this paper, By means of many experiments, it has been found that water soluble polymer is able to be evenly soluble in water glass, and certain valuable conclusions have been concluded.

Solubility measurement,correlation and thermodynamic properties of 2,3,4-trichloro-1,5-dinitrobenzene in fifteen mono-solvents at temperatures from 278.15 to 323.15 K

The solubility of 2,3,4-trichloro-1,5-dinitrobenzene(TCDNB) was measured by a laser dynamic method over the temperature range from 278.15 K to 323.15 K under 0.1 MPa in fifteen mono-solvents(methanol,ethanol,isopropanol,n-butanol,toluene,dichloromethane,chloroform,tetrachloromethane,1,2-dichloroethane,acetone,ethyl acetate,acetonitrile,N-methylpyrrolidone(NMP),N,Ndimethylformamide dimethyl sulfoxide(DMF),dimethyl sulfoxide(DMSO).The solubility of TCDNB could be increased with increasing temperature in fifteen mono-solvents.TCDNB solubility is in the following order at 298.15 K:NMP>DMF>DMSO>toluene>acetone>ethyl acetate>dichloromethane>1,2-dich loroethane>chloroform>acetonitrile>tetrachloromethane>methanol>ethanol>n-butanol>isopropanol.The KAT-LSER model was used to investigate the solvent effect,which revealed that the hydrogen bond acidity of solvents has a greater effect on TCDNB solubility.The van't Hoff model,the modified Apelblat model,theλh model,and the non-random two liquid(NRTL)model were used to correlate the solubility of TCDNB.The calculated solubility data agreed well with the experimental data,and the modified Apelblat model fit best.Furthermore,the van't Hoff and Gibbs equations were also used to calculate the dissolution thermodynamic properties of TCDNB in various solvents.TCDNB dissolution could be an enthalpy-driven,non-spontaneous,and endothermic process in fifteen mono-solvents.The determination and fitting solubility of TCDNB,as well as the calculation of its thermodynamic properties,would be critical in the purification and crystallization of its preparation process research.

Solubility of water in bridgmanite

Water in Earth's mantle plays a critical role in both geodynamic and surficial habitability.Water in the upper mantle and transition zone is widely discussed,but less is known about the water in the lower mantle despite it constituting over half of Earth's mass.Understanding the water storage in Earth's lower mantle relies on comprehending the water solubility of bridgmanite,which is the most abundant mineral both in the lower mantle and throughout Earth.Nevertheless,due to limited access to the lower mantle,our understanding of water in bridgmanite mainly comes from laboratory experiments and theoretical calculations,and a huge controversy still exists.In this paper,we provide a review of the commonly employed research methods and current findings concerning the solubility of water in bridgmanite.Potential factors,such as pressure,temperature,compositions,etc.,that influence the water solubility of bridgmanite will be discussed,along with insights into future research directions.

Measurement and correlation of solubility of 9-fluorenone in 11 pure organic solvents from T = 283.15 to 323.15 K

In this work, the solubility data of 9-fluorenone in 11 pure solvents(methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, acetonitrile, ethyl formate, ethyl acetate, dimethyl sulfoxide, n-hexane)were measured by the gravimetric method from 278.15 K to 318.15 K under atmospheric pressure. The results showed that the solubility of 9-fluorenone in all tested solvents increased with the raised temperature. The solubility data were correlated by the modified Apelblat equation, λh model and NRTL(nonradom two fluid) model. The average relative deviation(ARD) correlated by three thermodynamic models in different solvents was all below 5%, which indicated that the three thermodynamic models fit the solubility data well. Furthermore, the mixing thermodynamic properties of 9-fluorenone in pure solvent systems were calculated via NRTL model. The results indicated the dissolution process of 9-fluorenone is spontaneous and entropically favorable. The solubility and the mixing thermodynamic properties provided in this paper would play an important role in industrial manufacture and follow-up operation of 9-fluorenone.

Solubility study and selective purification of HMX explosive in organic electrolyte solution of zinc acetate/diethylene glycol

In this study, an organic electrolyte solution based on zinc acetate/diethylene glycol(ZA/DEG) is introduced for the selective purification of cyclotetramethylene tetranitramine(HMX) high explosive from its identical homologue cyclotrimethylene trinitramine(RDX). The dielectric constant of various organic solutions were investigated through Electrochemical Impedance Spectroscopy(EIS) in the range of 1.0 Hz—30 MHz. and some quantum-chemical descriptors of RDX and HMX dissolutions in the ZA cosolvent were analyzed using Density Functional Theory(DFT). The results show dielectric constant and solubility of RDX is higher than that of HMX, and by increasing of ZA concentration in DEG solvent, the values of dielectric constants were enhanced. Furthermore, the presence of ZA cosolvent on the solubility of two explosives was statistically investigated by Central Composite Design(CCD) of experiment, and some solubility parameters including activity coefficient, dissolving enthalpy, and mixing enthalpies were determined. The experimental results indicate that the weight ratio of RDX to HMX solubility in the proposed organic electrolyte changes up to 30 times, which provides a selective and sequential separation method to separate two materials with similar chemical properties with a separation efficiency>98% and HMX purity> 99.8%. The X-Ray Diffraction(XRD) analysis, High-Performance Liquid Chromatography(HPLC), Laser-Induced Breakdown Spectroscopy(LIBS), and Fourier Transform Infrared Spectroscopy(FT-IR) approves the acceptable quality of the separated materials. The proposed method makes the efficient and safe purification of high-quality HMX for application in oil and gas well perforating gun charges, using a nonvolatile and inflammable organic electrolyte.

Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA

To ensure proper dosage of a drug,analytical quantification of it in biofluid is necessary.Liquid chromatography mass spectrometry(LC-MS)is the conventional method of choice as it permits accurate identification and quantification.However,it requires expensive instrumentation and is not appropriate for bedside use.Using soluble epoxide hydrolase(sEH)inhibitors(EC5026 and TPPU)as examples,we report development of a nanobody-based enzyme-linked immunosorbent assay(ELISA)for such small molecules and its use to accurately quantify the drug chemicals in human samples.Under optimized conditions,two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL,respectively,and two order of magnitude linear ranges with high precision and accuracy.The assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate EC5026.In addition,the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory potency.The results indicate that nanobody-based ELISA methods can efficiently analyze drug like compounds.These methods could be easily implemented by the bedside,in the field in remote areas or in veterinary practice.This work illustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy.Attributes of nanobody based pharmaceutical assays are discussed.

Enhancing effect of choline chloride-based deep eutectic solvents with polyols on the aqueous solubility of curcumin–insight from experiment and theoretical calculation

The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents(DESs) on the aqueous solubility of curcumin(CUR) via experiment and theoretical calculation. Choline chloride-based DESs with polyols 1,2-propanediol(1,2-PDO), 1,3-propanediol, ethylene glycol, and glycerol as hydrogen bond donors were prepared and used as co-solvents. The CUR aqueous solubility increased with increasing the DESs content at temperature of 303.15-318.15 K, especially in aqueous ChCl/1,2-PDO(mole ratio 1:4) solutions. The positive apparent molar volume values and reduced density gradient analysis confirmed the existence of strong interactions between CUR and solvent. The van der Waals interactions and hydrogen bonding coexisted in DESs monomer retained the stability of DESs structure after introducing CUR. Moreover,the lower interaction energy of DESs…CUR system than that of the counterpart DESs further proved the strong interaction between CUR and DESs. The lowest interaction energy of ChCl/1,2-PDO…CUR system indicated that this system was the most stable and ChCl/1,2-PDO was promising for CUR dissolution.This work provides efficient solvents for utilizing curcumin, contributing to a deep insight into the interactions between DES and CUR at the molecular level, and the role of DESs on enhancing drugs solubility.

Simulation calculation of solubility of insoluble compound M_mA_a in complex system

A simulation calculation model for the solubility of insoluble compound MmAa in complex system was established.According to coordination equilibrium principle,relevant dissociation reaction,complexation reaction,self-complexation reaction and protonation reaction during insoluble compound dissolving were considered and then the mass balance equations about solubility calculation were obtained.In the case analysis,the solubility of silver chloride in ammonia system was obtained by simulation calculation,and curved surface charts of thermodynamic equilibrium about the total concentration of silver ions,pH and concentration of ammonia ions were drawn correspondingly.The results show that under the conditions of room temperature and 6 mol/L ammonia concentration,the calculated solubility value of silver chloride(34 g/L) is close to the actual value(31 g/L),demonstrating that this model is suitable for solubility calculation of insoluble compound MmAa in the complex system.

Measurement and model of density,viscosity,and hydrogen sulfide solubility in ferric chloride/trioctylmethylammonium chloride ionic liquid

The density and viscosity of ferric chloride/trioctylmethylammonium chloride ionic liquid(rFeCl_(3)/[A336]Cl)with different molar ratios(r=0.1-0.8)of FeCl_(3) to[A336]Cl were measured at temperatures from 313.15 to 358.15 K and atmospheric pressure.The density and viscosity data were fitted by the relevant temperature variation equations,respectively.The variation of density and viscosity with temperature and r was obtained.The solubility of rFeCl_(3)/[A336]Cl to H_2S was measured at temperatures from 318.15 to 348.15 K and pressures from 0 to 150 kPa.The effects of temperature,pressure,and r on the solubility of H_(2)S were discussed.The reaction equilibrium thermodynamic model(RETM)was used to fit the H_(2)S solubility data,and the average relative error was less than 1.3%,indicating that the model can relate the solubility data well.And Henry's constant and chemical reaction equilibrium constant were obtained by the RETM fitting.The relationships of Henry's constant and chemical reaction equilibrium constant with temperature and r were analyzed.

Solubility study of hydrogen in direct coal liquefaction solvent based on quantitative structure–property relationships model

Direct coal liquefaction(DCL)is an important and effective method of converting coal into high-valueadded chemicals and fuel oil.In DCL,heating the direct coal liquefaction solvent(DCLS)from low to high temperature and pre-hydrogenation of the DCLS are critical steps.Therefore,studying the dissolution of hydrogen in DCLS under liquefaction conditions gains importance.However,it is difficult to precisely determine hydrogen solubility only by experiments,especially under the actual DCL conditions.To address this issue,we developed a prediction model of hydrogen solubility in a single solvent based on the machine-learning quantitative structure–property relationship(ML-QSPR)methods.The results showed that the squared correlation coefficient R^(2)=0.92 and root mean square error RMSE=0.095,indicating the model’s good statistical performance.The external validation of the model also reveals excellent accuracy and predictive ability.Molecular polarization(a)is the main factor affecting the dissolution of hydrogen in DCLS.The hydrogen solubility in acyclic alkanes increases with increasing carbon number.Whereas in polycyclic aromatics,it decreases with increasing ring number,and in hydrogenated aromatics,it increases with hydrogenation degree.This work provides a new reference for the selection and proportioning of DCLS,i.e.,a solvent with higher hydrogen solubility can be added to provide active hydrogen for the reaction and thus reduce the hydrogen pressure.Besides,it brings important insight into the theoretical significance and practical value of the DCL.

Eukaryotic expression, purification and activity characterization of human soluble DSG2 extracellular domain protein

Objective:To construct a secretory eukaryotic expression vector of DSG2 fused with the Fc region of the human IgG,to validate its expression in 293T cells,and to purify the secretory protein with biological activity.Methods:The DSG2 extracellular domain fragment gene(DSG2ex),was amplified by PCR,and was inserted into the eukaryotic expression plasmid pCMV3-IgG1 to construct the recombinant eukaryotic expression plasmid-pCMV3-DSG2ex-IgG1.The successfully constructed eukaryotic expression plasmid was transfected into 293T cells to express and secrete DSG2 extracellular domain protein.The targeted protein was purified from the cell culture supernatant by Protein A affinity chromatography and confirmed by Western Blotting and ELISA.Results:The pCMV3-DSG2ex-IgG1 eukaryotic expression plasmid was successfully constructed.The highest protein expression level was obtained with 293T cells after 96 h of transfection.The relative molecular mass of the purified product was between 100 and 130 kDa was estimated by SDS-PAGE,which was consistent with the expectation.The yield of the purified protein reached 0.8 mg/ml with a purity over 90%.The purified DSG2 extracellular domain protein with IgG1 tag was recognized by IgG monoclonal antibodies by Western blotting.Moreover,the ELISA results showed that the prepared DSG2 extracellular domain protein had significant binding activity to human type 55 adenovirus Fiber Knob protein(HAdV-55).Conclusion:A simple and efficient method for eukaryotic expression and purification of human soluble DSG2 extracellular domain protein was successfully established,and biologically active DSG2 extracellular domain protein was purified,which laid the foundation for the later study of its protein function and anti-adenovirus drugs.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage

BACKGROUND Several studies of spontaneous intracerebral hemorrhage(SICH)patients have shown apoptotic changes in brain samples after hematoma evacuation.However,there have been no data on the association between blood concentrations of soluble fas(sFas)(the main surface death receptor of the extrinsic apoptosis pathway)and the prognosis of spontaneous intracranial hypotension(SIH)patients.AIM To determine whether there is an association between blood sFas concentrations and SICH patient mortality.METHODS We included patients with severe and supratentorial SIH.Severe was defined as having Glasgow Coma Scale<9.We determined serum sFas concentrations at the time of severe SICH diagnosis.RESULTS We found that non-surviving patients(n=36)compared to surviving patients(n=39)had higher ICH score(P=0.001),higher midline shift(P=0.004),higher serum sFas concentrations(P<0.001),and lower rate of early hematoma evacuation(P=0.04).Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality(odds ratio=1.070;95%confidence interval=1.014-1.129;P=0.01)controlling for ICH score,midline shift,and early hematoma evacuation.CONCLUSION The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

紫果西番莲‘满天星’二倍体与三倍体生长生理指标的比较

以紫果西番莲‘满天星’二倍体与三倍体无菌苗为研究材料,测定不同年度生长阶段的生长和生理指标,比较其差异性,并进行相关性分析。结果表明:2种‘满天星’苗木的苗高、地径持续增长,表现出三倍体‘满天星’苗高较小、地径较大的特点。同一位置叶片的叶片长、叶片宽、叶柄长随时间变化呈先增大后减小的趋势。随时间的变化2种‘满天星’的茎节数量逐渐一致,三倍体‘满天星’苗木表现出短粗的特征。在测定期中三倍体‘满天星’可溶性蛋白和叶绿素含量大于二倍体,测量前期可溶性糖含量小于二倍体,后期大于二倍体。不同倍性的西番莲的叶绿素a、叶绿素b、类胡萝卜素与苗高、茎节、地径呈负相关,与叶长、叶柄长呈正相关;但可溶性糖、可溶性蛋白与生长指标相关性略有差异。综上所述,三倍体与二倍体的生长生理指标存在差异,且可溶性糖、可溶性蛋白与生长指标相关性存在差异。

黄河兰州段一株优势藻的分离鉴定及光照、pH、温度对其生长的影响

为探究黄河兰州段水域的优势绿藻,从金牛街码头和中山桥水域采集水样,分离得到4株微藻,初步鉴定为小球藻属(Chlorella)、链带藻属(Desmodesmus)、近头状尖胞藻属(Raphidocelis)和空星藻属(Coelastrum),依次命名为Chlorella sp.HH13,Desmodesmus sp.HH2C,Raphidocelis sp.HHTXZ和Coelastrum sp.HH4.4株藻培养9 d后生物量水平表现为HH13>HH2C>HHTXZ>HH4,选取HH13作为目标藻种探究其在最佳光照、pH和温度条件下的生物量、光合色素、可溶性蛋白以及可溶性糖的积累.在BG11培养基中培养HH13,确定最佳光照强度为6000 Lux,类胡萝卜素和总叶绿素含量达到最大值,分别为2.029和6.929 mg·g^(-1),可溶性糖和可溶性蛋白的含量也最高,分别为0.285%和7.661 mg·g^(-1);最佳pH值为7,生物量最高可达0.297 g·L^(-1),类胡萝卜素和总叶绿素含量达到最大值,分别为2.753和9.711 mg·g^(-1),可溶性糖和可溶性蛋白含量也最高,分别为0.484%和5.674 mg·g^(-1);最佳温度为28℃,生物量最高为0.289 g·L^(-1),类胡萝卜素和总叶绿素含量分别为1.796和6.073 mg·g^(-1),可溶性糖含量为0.288%,可溶性蛋白的含量为5.898 mg·g^(-1).最终得到HH13生长的最佳光照强度为6000 Lux、pH值为7、温度为28℃.