Multisolvent Systems Research Articles

Preparative separation of the constituents from Ginkgo biloba L. leaves by a combination of multi-stage solvent extraction and countercurrent chromatography.

In this study, we employed a combination approach for the preparative separation of constituents from Ginkgo biloba L. leaves. It involved multi-stage solvent extractions utilizing two-phase multi-solvent systems and countercurrent chromatography (CCC) separations using three different solvent systems. The n-heptane/ethyl acetate/water (1:1:2, v/v) and n-heptane/ethyl acetate/methanol/water (HepEMWat, 7:3:7:3, v/v) solvent systems were screened out as extraction systems. The polarities of the upper and lower phases in the multi-solvent systems were adjustable, enabling the effectively segmented separation of complex constituents in G. biloba L. The segmented products were subsequently directly utilized as samples and separated using CCC with the solvent systems acetate/n-butanol/water (4:1:5, v/v), HepEMWat (5:5:5:5, v/v), and HepEMWat (9:1:9:1, v/v), respectively. As a result, a total of 11 compounds were successfully isolated and identified from a 2g methanol extract of G. biloba L through two-stage extraction and three CCC separation processes; among them, nine compounds exhibited high-performance liquid chromatography purity exceeding 85%.

Strategy for Measuring Thermodynamic Factors in Lithium Electrolytes with Two Neutral Solvents

Thermodynamic factors, which convert species concentration gradients (∇ci) into electrochemical-potential gradients (∇μi), are essential quantities within concentrated-solution transport theory. Originally suggested by Darken [1], thermodynamic factors (χij) are defined through thermodynamic derivatives, asRT χij = yi ∂μi/∂yj,in which yi is the particle fraction of species i, R the universal gas constant, and T the absolute temperature. Accurate parameterisation of thermodynamic factors is important for the practical modelling of electrochemical systems, because they quantify how concentration polarization translates into concentration overpotential.The most common electrochemical approach to thermodynamic-factor characterisation is the concentration-cell method, whereby the steady-state voltage difference between two reservoirs containing different salt concentrations – i.e., the liquid-junction potential – is measured. A series of such measurements over a range of salt concentrations suffices to produce a functional form of χij, provided that the transference number is known from an auxiliary experiment. This method is well-established for binary electrolytes (i.e., a single salt in a neutral solvent), and has been used to produce ample data in the lithium-battery literature, for example by Nyman et al. [2], Landesfeind and Gasteiger [3], and Wang et al. [4].In practice, however, many electrochemical devices – especially lithium batteries – use electrolytes that incorporate a mixture of solvents. The relationship between voltage readings and thermodynamic factors in concentration-cell experiments becomes immediately unclear in these more complicated systems. In this talk we consider the thermodynamics of multi-solvent systems in the simplest case: that of two neutral solvents and a binary electrolyte, such as the LiPF6:EC:EMC solutions commonly used in Li-ion battery applications. Experimental procedures for characterising independent thermodynamic factors in two-solvent systems will be discussed.

Methodologies for Design, Characterization and Testing of Electrolytes that Enable Extreme Fast Charging of Lithium-ion Cells

Selection, testing and validation of electrolyte candidates for Li-ion cells are discussed, based on a 10-minute target for extreme fast charge (XFC). A combination of modeling and laboratory measurements create a timely and synergistic approach to identifying candidate electrolyte formulations. Multi-solvent systems provide a balanced set of properties, wherein lower molecular-weight solvents offer reduced viscosity, increased species diffusivity, and mitigation of concentration polarization at high charge rates. Carefully selected formulations can exhibit peak conductivity and usable conductivity range of two to three times that of the baseline EC-EMC (3:7, wt.) + LiPF6. Candidates are also chosen based on stability and longevity within the cell environment. Lab testing coincides with property predictions from the Advanced Electrolyte Model (AEM) and a macro-scale cell model. Cell testing utilized coin and pouch cells having NMC532 or NMC811 cathodes with graphite electrodes. Results indicate combinations of low-molecular weight solvents are key for fast-charge electrolytes as they extend the useful conductivity range to both low and higher salt concentrations, and possess higher self-diffusivities compared to conventional solvents. This reduces impacts from concentration polarization. The choice of electrolyte also influences the tendency for lithium metal deposition at the anode, as showcased by experimental and modeling results herein.

Coordination-crosslinked polyimide supported membrane for ultrafast molecular separation in multi-solvent systems

Substrate modification of thin film composite (TFC) membranes by various crosslinkers is generally required for organic solvent nanofiltration (OSN) application, to enhance the membrane stability and solvent resistance, which however leads to the permeance decline. In this contribution, coordination-crosslinked polyimide substrate is developed for the first time, which is different with those covalently-crosslinked substrates, and achieves the enhanced solvent resistance, improved hydrophilicity and optimized porous microstructure simultaneously. The effects of the alkaline coagulation bath, subsequent ion exchange, and further solvent activation are investigated. The resultant TFC membrane breaks through the typical permeability-selectivity trade-off of OSN membranes successfully, exhibiting an astonishingly superior solvent permeance (1.5–2 times the highest data) (65.2 LMH/bar for methanol, 33.1 LMH/bar for ethanol and 59.1 LMH/bar for acetone) to previously reported polymeric-based TFC OSN membranes with a competitive solute rejection (>98% for Rose Bengal). This study is believed to provide a new orientation in the development of the desirable substrate for the high-performance OSN composite membrane and other separation applications.

Anion Selection Criteria for Water‐in‐Salt Electrolytes

AbstractWater‐in‐salt electrolytes have enabled the development of novel high‐voltage aqueous lithium‐ion batteries. This study explores the reasons why analogous sodium electrolytes have struggled to reach the same level of electrochemical stability. Solution structure and electrochemical stability are compared for 11 sodium salts, selected among the major classes of salts proposed for highly concentrated electrolytes. The water environment established for each anion is related to its position in the Hofmeister series and a surprisingly strong correlation between the chaotropicity of the anion and the resulting electrochemical stability of the electrolyte is found. The search for suitable sodium salts is complicated by the fact that higher salt concentrations are needed than for their lithium equivalents. Reaching such a high concentration of >25 mol kg−1 with one or a combination of multiple sodium salts that have the desired properties remains a major challenge. Hence, alternative approaches such as multisolvent systems should be explored. The water solubility of NaTFSI can be increased from 8 to 30 mol kg−1 in the presence of ionic liquids. Such a ternary electrolyte enables stable cycling of a 2 V class sodium‐ion battery based on the NaTi2(PO4)3/Na2Mn[Fe(CN)6] electrode couple for 300 cycles at 1C with a Coulombic efficiency of >99.5%.

Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics.

Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.

Lattice Boltzmann equation for mass transfer in multi solvent systems

The key problem for simulating mass transfer in multi solvent systems is the concentration jump at the phase interface described by Henry’s law. In the present paper, after analyzing the shortages of Fick’s law in describing mass transfer in multi solvent systems, the revised Fick’s law that can be applied to mass transfer in multi solvent systems is proposed. The corresponding governing equation can describe the concentration jump directly without any modification and doesn’t need to transform the scalar or parameters. To solve the governing differential equation based on the revised Fick’s law, a multi-relaxation-time (MRT) lattice Boltzmann equation (LBE) is constructed. Five test cases containing both the transient and steady mass transfer problems in multi solvent systems with straight or curved interfaces are conducted to validate the proposed MRT LBE. The results show that proposed MRT LBE is easy in implementation and capable of simulating both steady and transient mass transfer in multi solvent systems. In addition, the comparison indicates that the MRT LBE could have better accuracy than single-relaxation-time (SRT) LBE by keeping an optimal relation between two relaxation times.

Prediction of Electrolyte Conductivity: Results from a Generalized Molecular Model Based on Ion Solvation and a Chemical Physics Framework

Ionic conductivity is a foremost transport property that is extensively used to characterize and screen electrolyte systems. Although bulk measurements are done on the macroscopic scale, electrolytic conductivity has its foundation on molecular-scale interactions between solvent and ionic species. Correct interpretations of these molecular interactions and related quantities enable a balanced, comprehensive understanding of conductivity behavior with respect to system conditions (solvent composition, salt concentration and temperature). This work introduces a new methodology that achieves accurate predictions of electrolyte conductivity for a wide range of conditions, based on molecular, physical, and chemical terms. The formalism is universal, making it valid for aqueous and non-aqueous systems alike. The immediate application of the resultant model is candidate electrolytes for lithium-ion and sodium-ion batteries, although many other applications abound for systems that utilize liquid electrolytes. Conductivity predictions are compared to experimental data for a number of electrolytes over a wide range of conditions, demonstrating that exceptional accuracy is attained because the robust model captures multiple salient contributions to conductivity behavior. Model accuracy is well maintained over multi-solvent systems and for extended salt concentrations.

The surface activity of polymers in cosolvated systems determined from computational simulation

The present body of literature fails to adequately address the need for simulation metrics which determine the surface activity of target species in single or multi-solvent systems. Within this work a new property determinable by computational molecular dynamics simulation is detailed. That is the surface parameter, which is an indicator of the placement of a molecule with respect to the interface. Simulations were carried out on polyalkanes in alcohol co-solvated systems to verify systematically that the OPLS-AA force fields can accurately describe the solvation of low molecular weight polyalkanes with increased alcohol content. This parameter and the associated code are helpful in identifying quickly if a molecule is surface active, especially in mixed solvent systems. The code for the determination of this property is written in FORTRAN, a widespread and readily available package on most supercomputing systems where GROMACS is deployed.

Optimal Solvent Screening for the Crystallization of Pharmaceutical Compounds from Multisolvent Systems

In this study, an effort has been made to predict the solid–liquid equilibrium (SLE) behavior of different solids (pharmaceuticals) in many common solvents and their mixtures. A modified optimizati...

Optimal Separation of Glycerol and Methyl Oleate via Liquid−Liquid Extraction

To meet the ASTM D-6751-02 Standard for biodiesel, impurities, particularly glycerol, must be reduced to acceptable levels. Liquid−liquid extraction (i.e., solvent partitioning) is commonly used to achieve this standard. Evaluation of the technical feasibility of a single-stage mixer−settler liquid−liquid equilibrium process to separate glycerol and methyl oleate (as a model for biodiesel) was carried out based on the following criteria: (a) a volume ratio of the liquid phases close to 1:1, (b) a high recovery of biodiesel, (c) a short residence time of the liquid phases in the settler, and (d) achievement of the ASTM Standard for glycerol mass fraction of 0.0002 or less. Eight liquid−liquid extraction processes using different combinations of three potential solvents, hexane, methanol, and water, were studied. All data for the optimal compositions of each solvent system were obtained by calculations using the UNIFAC activity coefficient model, and no experimental measurements were done. Extraction using multisolvent systems containing hexane, methanol, and water were found to be technically feasible and gave the best results.

Reverse Schreinemakers Method for Experimental Analysis of Mixed-Solvent Electrolyte Systems

A method based on Schreinemakers’s tie-line theory of 1893 is derived for determining the composition and phase amounts in solubility experiments for multi-solvent electrolyte systems. The method uses the lever rule in reverse compared to Schreinemakers’s wet residue method, and is therefore called the reverse Schreinemakers (RS) method. The method is based on simple mass balance principles similar to the wet residues method. It allows for accurate determination of the mixed-solvent phase composition even though part of the solvent may precipitate as complexes between solvent and salt. Discrepancies from determining the composition of salt mixtures by pH titration are discussed, and the derived method significantly improves the obtained result from titration. Furthermore, the method reduces the required experimental work needed for analysis of phase composition. The method is applicable to multi-solvent systems and may be used for the determination of solid-phase compositions, similar to Schreinemakers’s original “rest” method. An example calculation is presented for the Na2CO3-NaHCO3-MEG-H2O system.

A differential approach to calculating osmotic equilibrium for multisolvent systems

A differential approach to the calculation of osmotic pressure of multisolvent systems within the Lewis–Randall framework is presented in this paper. Exact differential equations relating the osmotic pressure and the system composition along paths of constant solvent chemical potential are obtained and numerically solved. Although even for the simple case of an ideal solution no analytic expression for the osmotic pressure can be obtained, the system of differential equations does not pose numerical difficulties to be solved. Examples of the use of the proposed methodology are presented using the two-suffix Margules and Flory–Huggins equations, allowing an assessment of the influence of liquid-phase non-ideality on the performance of the method, and showing that it can be applied even for systems wherein liquid–liquid phase equilibrium occurs.

Lung DNA Adducts Detected in Human Smokers Are Unrelated to Typical Polyaromatic Carcinogens

Several studies have reported the presence of DNA adducts derived from benzo(a)pyrene and other polyaromatics by 32P-postlabeling/TLC by measuring diagonal radioactive zones (DRZs) in lung tissues of human smokers. However, our experimental studies in rodent models, which used modified chromatographic conditions to obtain distinct adduct spots, suggested that cigarette smoke-related lipophilic DNA adducts may not be derived from polycyclic aromatic hydrocarbons (PAHs) or aromatic amines. In the present study, we have performed similar analysis of human lung tissues to study the chemical nature of DNA adducts. Fifty human lung tissues from cancer patients (ages 42-83 years) with active, ex-, or never-smoking status were analyzed for highly lipophilic DNA adducts by nuclease P1- and n-butanol enrichment-mediated 32P-postlabeling assay. All DNA samples yielded low to highly intense adduct DRZs when adducts were resolved by PEI-cellulose TLC in standard high-salt, high-urea solvents. Adduct burden ranged from 6.6 to 2930 per 10(10) nucleotides. However, when adducts were resolved in a different solvent system comprising of high-salt, high-urea in direction 3 and dilute ammonium hydroxide in direction 4, which retained adducts derived from PAHs and aromatic amines on the chromatograms, this yielded no detectable adducts from human lung DNAs. Furthermore, analysis of human lung DNAs mixed with reference adducted DNAs in multisolvent systems confirmed an absence of PAH- and aromatic amine-derived adducts in human smoker lung DNA. To determine the origin of cigarette smoke-associated DNA adducts, calf thymus DNA was incubated with formaldehyde and acetaldehyde, which are known to be present in cigarette smoke in significant quantities. Analysis of purified DNAs by 32P-postlabeling resulted in adduct DRZs in the aldehyde-modified DNAs when adducts were resolved in standard urea-containing solvents, but no adducts were detected when the ammonium hydroxide-based solvent was used, suggesting that even nonpolyaromatic electrophiles can result in adduct DRZs on the chromatograms similar to those from PAH metabolites. Taken together, our data demonstrate that cigarette smoke-associated lung DNA adducts appear on chromatograms as DRZs, consistent with the literature, but they are not related to PAHs and aromatic amines.

A Four-Component Study for Estimating Solubilities of a Poorly Soluble Compound in Multisolvent Systems Using a Scheffé-Type Model

AbstractThe equilibrium solubility of GF1209184, a poorly soluble compound with potential use as a multidrug resistance (MDR) inhibitor of P-glycoprotein, was studied at 25°C in multisolvent systems containing polyethylene glycol 300, polysorbate 80, ethanol, and water. The objective was to determine the feasibility, with respect to solubility, of formulating a concentrated formulation for product presentation in an ampule or vial. Data were fit to a quadratic Scheffe-type model with excellent correlation between the experimentally determined and fitted equilibrium solubilities (R2 = 0.9875, slope = 1.043). Solubilities greater than 4 mg base/mL at 25°C were determined for mixtures in this study, making it feasible, with regard to solubility, to formulate a concentrated vial or ampule formulation. Maximum solubility, however, was dependent on the ability to adjust the apparent pH to ≤3.5 in the cosolvent/surfactant systems studied.

Optimization of a multisolvent composition in RPHPLC: Generalization to non- ideal peaks

When samples contain solutes at very different concentrations, the use of the classical resolution function to express the quality of the separation does not provide a true measure of peak overlap and is therefore unsuitable for optimization. Apart from this case, the validity of the optimum is highly dependent on the accuracy of the predicted retention surfaces and it is essential to restrict the parameter space in which optimum performance is sought. As a result, most interpretive optimization procedures become unreliable for optimizing the composition of multisolvent systems in RPHPLC, particularly for non-ideal peaks. These difficulties can be overcome by the method proposed here: the ability, by means of a criterion, called CRIT, to select a restricted range of composition in order to enhance the accuracy of the response surface is developed for non-ideal peaks. The best composition within this selected range is then determined by using a modified resolution function. The performance of this procedure is discussed with some illustrative examples.

Optimization of a multisolvent composition in RP-HPLC: Convenient criterion for preliminary search for the best eluent strength

Interpretive methods are very commonly used to direct the search for the optimum solvent composition. For multisolvent systems, the composition search space is often reduced to one straight line (ternary systems with two organic modifiers), three straight lines (three ternary systems with each possible pair of the organic modifiers of the tetrahedron) — or a plane delimited by a triangle (quaternary systems inside the solvent tetrahedron). In each case, the space is restricted by binary compositions of equal solvent strength, in such a way that through it, the analysis time remains approximately constant. This restricted space is defined without taking into account any selectivity criterion between peaks, and consequently, if a given pair of peaks is badly resolved with the considered binary solvents, the probability of any mixture of them improving the peak selectivity will be very low. The ability to calculate the retention models in a binary solvent system from two linear gradient runs, allows the prediction of the selectivity for each pair of solutes into each binary solvent system (ACN/Water, MeOH/Water, THF/Water) from six preliminary linear gradient runs, and then, to determine and eliminate all the sets of isoeluotropic binary compositions that will offer little hope of giving useful separation conditions with multisolvent systems and, at the same time, to select the most promising set of binary compositions. The selectivity and the total time of the chromatogram are the two parameters that are considered for this search. When several possiblities are found, priority is given to the simplest solvent system (binary rather than ternary and ternary rather than quaternary). Reducing the number of preliminary experiments and improving the accuracy of the predicted optimum are the two objectives of this approach. Its practical interest is discussed by comparing the results obtained for an illustrative separation to those obtained with another existing method.

The fitting of scheffé-type models for estimating solubilities of multisolvent systems

In pharmaceutical studies it is often necessary to dissolve a slightly polar drug in a mixture of water and one or more cosolvents, such as ethanol, glycerol, and propylene glycol, to increase the drug's solubility. It is also of interest to know whether a maximum in the solubility profile of the drug exists in the mixture of solvents and if so, where. Scheffé-type models are particular forms of polynomial equations that can be used with variables that are expressed as proportions of the total mixture. These models are simple in form, yet are extremely versatile in terms of modeling the linear and nonlinear blending properties of the constituents in the mixtures. Several data sets are presented to illustrate the fitting of the Scheffé-type models for modeling the solubility of multisolvent systems.

A molecular approach to electrolyte solutions: Phase behavior and activity coefficients for mixed-salt and multisolvent systems

A molecular formulation based on modern liquid state theory is applied to the properties and phase behavior of electrolyte systems involving volatile species. The theory goes beyond the usual Debye-Hückel and Pitzer correlations for treating concentrated solutions. The optimized random phase resummation of the cluster diagrams as exemplified in the EXP theory for the cation-cation, cation-anion, and anion-anion distributions is used for the ionic species. This theory represents an improvement over the MSA approach. Electrolyte solutions such as water-salt, ammonia-salt, mixed salts, and mixed-solvent systems are investigated. The usual salt properties, such as osmotic and mean activity coefficients and other thermodynamic properties, are calculated. The predictions are accurate to saturation limits.