Machine learning prediction of methane,ethane,and propane solubility in pure water and electrolyte solutions:Implications for stray gas migration modeling

Hydraulic fracturing is an effective technology for hydrocarbon extraction from unconventional shale and tight gas reservoirs.A potential risk of hydraulic fracturing is the upward migration of stray gas from the deep subsurface to shallow aquifers.The stray gas can dissolve in groundwater leading to chemical and biological reactions,which could negatively affect groundwater quality and contribute to atmospheric emissions.The knowledge oflight hydrocarbon solubility in the aqueous environment is essential for the numerical modelling offlow and transport in the subsurface.Herein,we compiled a database containing 2129experimental data of methane,ethane,and propane solubility in pure water and various electrolyte solutions over wide ranges of operating temperature and pressure.Two machine learning algorithms,namely regression tree(RT)and boosted regression tree(BRT)tuned with a Bayesian optimization algorithm(BO)were employed to determine the solubility of gases.The predictions were compared with the experimental data as well as four well-established thermodynamic models.Our analysis shows that the BRT-BO is sufficiently accurate,and the predicted values agree well with those obtained from the thermodynamic models.The coefficient of determination(R2)between experimental and predicted values is 0.99 and the mean squared error(MSE)is 9.97×10^(-8).The leverage statistical approach further confirmed the validity of the model developed.

Machine learning with active pharmaceutical ingredient/polymer interaction mechanism:Prediction for complex phase behaviors of pharmaceuticals and formulations

The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations.In this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors.Under the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'screening.The results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.

Theoretical analysis of hydrogen solubility in direct coal liquefaction solvents

The cyclic hydrogenation technology in a direct coal liquefaction process relies on the dissolved hydrogen of the solvent or oil participating in the hydrogenation reaction.Thus,a theoretical basis for process optimization and reactor design can be established by analyzing the solubility of hydrogen in liquefaction solvents.Experimental studies of hydrogen solubility in liquefaction solvents are challenging due to harsh reaction conditions and complex solvent compositions.In this study,the composition and content of liquefied solvents were analyzed.As model compounds,hexadecane,toluene,naphthalene,tetrahydronaphthalene,and phenanthrene were chosen to represent the liquefied solvents in chain alkanes and monocyclic,bicyclic,and tricyclic aromatic hydrocarbons.The solubility of hydrogen X(mol/mol)in pure solvent components and mixed solvents(alkanes and aromatics mixed in proportion to the chain alkanes+bicyclic aromatic hydrocarbons,bicyclic saturated aromatic hydrocarbons+bicyclic aromatic hydrocarbons,and bicyclic aromatic hydrocarbons+compounds containing het-eroatoms composed of mixed components)are determined using Aspen simulation at temperature and pressure conditions of 373–523 K and 2–10 MPa.The results demonstrated that at high temperatures and pressures,the solubility of hydrogen in the solvent increases with the increase in temperature and pressure,with the pressure having a greater impact.Further-more,the results revealed that hydrogen is more soluble in straight-chain alkanes than in other solvents,and the solubility of eicosanoids reaches a maximum of 0.296.The hydrogen solubility in aromatic ring compounds decreased gradually with an increase in the aromatic ring number.The influence of chain alkanes on the solubility of hydrogen predominates in a mixture of solvents with different mixing ratios of chain alkanes and aromatic hydrocarbons.The solubility of hydrogen in mixed aromatic solvents is less than that in the corresponding single solvents.Hydrogen is less soluble in solvent compounds containing heteroatoms than in compounds without heteroatoms.

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.

Temperature-dependent solubility of Rebaudioside A in methanol/ethanol and ethyl acetate mixtures:Experimental measurements and thermodynamic modeling

The equilibrium solubility of Rebaudioside A(Reb A)FormⅡin binary mixtures of methanol/ethanol and ethyl acetate was quantitatively determined within the temperature range of 283.15—328.15 K at ambient pressure.The experimental findings indicate a positive correlation between the solubility of Reb A(FormⅡ)and both the temperature and the methanol/ethanol content in the solvent system.To describe the solubility data,six distinct models were employed:the modified Apelblat equation,theλh model,the combined nearly ideal binary solvent/Redlich—Kister(CNIBS/R—K)model,the van't HoffJouyban-Acree(VJA)model,the Apelblat-Jouyban-Acree(AJA)model,and the non-random two-liquid(NRTL)model.The combined nearly ideal binary solvent/Redlich—Kister model exhibited the most precise fit for solubility in methanol+ethyl acetate mixtures,reflected by an average relative deviation(ARD)of 0.0011 and a root mean square deviation(RMSD)of 12×10^(-7).Conversely,for ethanol+ethyl acetate mixtures,the modified Apelblat equation provided a superior correlation(ARD=0.0014,RMSD=4×10^(-7)).Furthermore,thermodynamic parameters associated with the dissolution of Reb A(FormⅡ),including enthalpy,entropy,and the Gibbs energy change,were inferred from the data.The findings underscore that the dissolution process is predominantly endothermic across the solvent systems examined.Notably,the entropy changes appear to have a significant influence on the Gibbs free energy associated with the dissolution of Reb A(FormⅡ),suggesting that entropic factors may play a pivotal role in the studied systems.

Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Tuning the solubility of polysulfides for constructing practical lithium-sulfur battery

Li-S batteries are regarded as one of the most promising candidates for next-generation battery systems with high energy density and low cost.However,the dissolution-precipitation reaction mechanism of the sulfur(S)cathode enhances the kinetics of the redox processes of the insulating sulfu r,which also arouses the notorious shuttle effect,leading to serious loss of S species and corrosion of Li anode.To get a balance between the shuttle restraining and the kinetic property,a combined strategy of electrolyte regulation and cathode modification is proposed via introducing 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoroprpyl ether(HFE)instead of 1,2-dimethoxyethane(DME),and SeS_(7)instead of S_8.The introduction of HFE tunes the solvation structure of the LiTFSI and the dissolution of intermediate polysulfides with Se doping(LiPSSes),and optimize the interface stability of the Li anode simultaneously.The minor Se substitution compensates the decrease in kinetic due to the decreased solubility of LiPSs.In this way,the Li-SeS_(7)batteries deliver a reversible capacity of 1062 and 1037 mAh g^(-1)with 2.0 and 5.5 mg SeS_(7)cm^(-2)loading condition,respectively.Besides,an electrolyte-electrode loading model is established to explain the relationship between the optimal electrolyte and cathode loading.It makes more sense to guide the electrolyte design for practical Li-S batteries.

Modeling solubility of oxaprozin and irbesartan in biorelevant complex solutions based on a combination of pH-dependent and micellar solubilization models

Biological solubility is one of the important basic parameters in the development process of poorly soluble drugs,but the current measurement methods are mainly based on a large number of experiments,which are time-consuming and cost-intensive.There is still a lack of effective theoretical models to accurately describe and predict the biological solubility of drugs to reduce costs.Therefore,in this study,osaprazole and irbesartan were selected as model drugs,and their solubility in solutions containing surfactants and biorelevant media was measured experimentally.By calculating the parameters of each component using the perturbed-chain statistical associating fluid theory(PC-SAFT)model,combined with pH-dependent and micellar solubilization models,the thermodynamic phase behavior of the two drugs was successfully modeled,and the predicted results were in good agreement with the experimental values.These results demonstrate that the model combination used provides important basic parameters and theoretical guidance for the development and screening of poorly soluble drugs and related formulations.

RETRACTED: Determination of the Mesalazine Solubility at Biorelevant Temperature

Short Retraction NoticeThis article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. The aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

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.

Soluble ST2:A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease

The increasing incidence of cardiovascular disease(CVD)is a significant global health concern,affecting millions of individuals each year.Accurate diagnosis of acute CVD poses a formidable challenge,as misdiagnosis can significantly decrease patient survival rates.Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs,but they can be influenced by various factors,such as age,sex,and renal function.Soluble ST2(sST2)is a novel biomarker that is closely associated with different CVDs.Its low reference change value makes it suitable for continuous measurement,unaffected by age,kidney function,and other confounding factors,facilitating risk stratification of CVDs.Furthermore,the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value.This review aims to provide a comprehensive overview of sST2,focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

Solubility determination and comparison ofβ-HMX and RDX in two binary mixed solvents(acetonitrile+water,nitric acid+water)

In order to remove hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX),the main impurity,in process of polymorphic transformation of octrahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine(HMX),the solubility ofβ-HMX and RDX in acetonitrile(ACN)+water in the temperature range of 288.15-333.15 K and in nitric acid(HNO_(3))+water in the temperature range of 298.15-333.15 K were measured by laser dynamic method.The results showed that the solubility of bothβ-HMX and RDX in binary mixed solvents increased monotonously as the temperature increase at a given solvent composition or with increasing of mole fraction of solvent(ACN and nitric acid).Solubility data were well correlated by the modified Apelblat equation,Jouyban-Acree model,Yaws equation and van't Hoff equation,and the Yaws equation achieved the best fitting results according to the relative error and the mean square error root.Furthermore,the solubility ofβ-HMX and RDX in binary mixed solvent was compared,based on the solubility difference and the solvent's own properties,the best separation degree ofβ-HMX and RDX was found when the mole fraction of nitric acid was 0.22 at room temperature,which provided data support for HMX crystallization in mixed solvent.The solubility differences between RDX andβ-HMX in mixed solvents were explained from the formation of intermolecular and intramolecular hydrogen bonds.

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 effect

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.

Study on the Rapid Method to Predict Longevity of Controlled Release Fertilizer Coated by Water Soluble Resin

The study discussed the rapid method to test and predict the longevity of controlled release fertilizers （CRFs） coated by water soluble resin by using the short-term leaching under higher temperature. Pure water dissolving incubation and higher temperature leaching were used to study the patterns of the nutrient release of the CRFs. The correlation analysis between the days at 25℃ and the hours at 80℃ of Trincote 1 and Trincote 2 for the same cumulative release rates were conducted. Patterns of cumulative nutrient release curve followed one factor quadratic regression equation at each given temperatures, and each of relative coefficient was bigger than 0.995. As the temperature increased, nutrients release of the CRFs increased. The longevity of resin coated CRFs were predicted by use of both the cumulative nutrients release equation at 80℃ and the regression equation of release time needed for the same cumulative release rates between 25 and 80℃. There were only 0.3-6.9% relative errors between the tested longevity and predicted one. In conclusion, the longevity of resin coated CRFs could be predicted more quickly and precisely by use of the higher temperature short-term leaching method than that of the traditional differential release rate. The longevity of resin coated CRF could be rapidly and precisely predicted in a few hours by application of the higher temperature shortterm leaching method.

Predication of Fhhh potential in PTA wastewater treatment

Ebis is the intelligent environmental biotechnological informatics software developed for judging the effectiveness of the microorganism strain in the industrial wastewater treatment system(IWTS) at the optimal status. The parameter, as the objective function for the judgment, is the minimum reactor volume( V _ min ) calculated by Ebis for microorganism required in wastewater treatment. The rationality and the universality of Ebis were demonstrated in the domestic sewage treatment system(DSTS) with the data published in USA and China at first,then Fhhh strain's potential for treating the purified terephthalic acid(PTA) was proved. It suggests that Ebis would be useful and universal for predicating the technique effectiveness in both DSTS and IWTS.

A THEORETIC METHOD TO PREDICT POLYMER SOLUBILITY PARAMETERS

A partition function and a complete thermodynamic description for pure polymer fluids have been investigated based on a self-avoid-walk lattice model. Caused by the introduction of Gibbs distribution into the Flory-Huggins theory, the partition function and the thermodynamic description depicted their dependence on temperature well. In the present study, we applied the theory to calculate polymer solubility parameters. The polymer solubility parameters predicted by our theory are well consistent with the experiment values.

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.

AN EQUATION OF STATE FOR AQUEOUS ELECTROLYTE SYSTEMS——Prediction of The Solubility of Natural Gas in Formation Water

A new equation of state(PHSMSA EOS)based on perturbation theory is developed for calculating high-pressure phase equilibria of aqueous electrolyte systems containing supercritical gases,light hydrocarbons andpolar components.The binary interaction parameters are determined:for ion-ion pairs by regression of ionicactivity coefficient data;for molecule-molecule pairs by fitting the VLE data of binary nonelectrolyte mixtures;and for ion-molecule pairs by fitting the gas solubility data of ternary gas-water-salt systems.The new EOShas been tested on the prediction of solubilities of methane,nitrogen and natural gas mixtures in brine.Sat-isfactory agreement with the experimental data measured by authors and other investigators is observed.

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.