Phase Equilibria In Solutions Research Articles

Method for direct measuring antibody affinity in biological sample.

We are reporting a new method to measure the affinity of specific antibodies in biological sample without the need of purification, or direct labeling. It was used to measure the affinity of anti-RBD (SARS-CoV2) IgG in plasma from Covid-19 recovered patient and vaccinated populations. Among the vaccinated population, we also measured the affinities of vaccine-induced antibodies against the RBD of the ancestral SARS-Cov-2 virus and the Omicron variants. The method has provided a quantitative way to evaluate antibodies produced by vaccination. The new method involves a classical Solution phase Equilibrium Titration step and an Imaging based Detection step (SET-ID). In the Solution phase Titration step, the antibody was kept at constant concentration (lower than the expected KD value) and mixed with various concentrations of antigen solution; In the Imaging Detection step, the amount of free antibody (not bound to antigen) at each antigen concentration was probed with small amount of microparticles coated with antigen and then the labeled secondary antibody. In this presentation, we will discuss the critical experimental condition, validation, and limitations. For verification, the binding curves of an antibody were compared using a well-established fluorescence spectroscopic-based method and the SET-ID method. The incubation time and the number of microparticles used in the second step were evaluated experimentally and theoretically to ensure minimal perturbation to the solution phase equilibrium, while the fraction of free antibody presented in the solution can still be measured by the signal on the microparticles.

Determination of Anti-drug Antibody Affinity in Clinical Study Samples Provides a Tool for Evaluation of Immune Response Maturation

Characterization of clinical anti-drug antibody (ADA) responses to biotherapeutics can be important to understanding the consequences of immunogenicity. ADA are expected to be polyclonal, with composition and affinities that evolve over time. Measuring ADA binding affinity can be complicated by the polyclonal nature of response, residual drug in sample, and low ADA levels. We developed a novel workflow to determine the apparent ADA affinity (KD) against a monoclonal antibody biotherapeutic, PF-06480605. An affinity capture elution pre-treatment step was used to isolate ADA and remove residual drug interference from samples. Solution-phase equilibrium incubation was performed using drug and sample ADA as variable and fixed binding interactants, respectively. Unbound ADA concentration was measured using a Singulex Erenna ligand-binding assay (LBA) method. Apparent ADA KD values were calculated using a custom R Shiny algorithm. KD values determined for ADA positive samples showed good correlation with other immunogenicity parameters, including titers and neutralizing antibody (NAb) activity with a general increase in affinity over time, indicative of a maturing immune response. Time of onset of high affinity responses (KD < 100 pM) varied between patients, ranging from 16 to 24 weeks. Antibody responses appeared monophasic at earlier time points, trending towards a biphasic response with a variable transition time and general increase in proportion of high affinity ADA over time. Herein, we provide a novel, sensitive bioanalytical method to determine the KD of ADA in clinical samples. The observed decrease in ADA KD is consistent with evidence of a maturing immune response.Graphical

Comprehensive operational parameter analysis of cross-flow hollow fiber membrane humidifier for humidification dehumidification desalination

Experimental results show that the cross-flow hollow fiber membrane contactor is the controlling component of the humidification dehumidification desalination system performance. Three sets of main operating conditions sensitivity analyses are performed numerically, including solution conditions (temperature, salinity, flow rate), air conditions (temperature, relative humidity, flow rate) and dimensionless parameters (number of heat transfer units, flow rate ratio of solution to air). Increasing flow rate ratio can effectively promote freshwater production rate before flow rate ratio reaches a critical value of 6.0. It is useful to improve moisture effectiveness by increasing number of heat transfer units. Solution inlet temperature has an exponential promoting effect on membrane flux, which is consistent with the exponential upward trend of the solution phase equilibrium humidity. Membrane flux increases dramatically at first and then slowly after solution flow rate exceeds 228 kg/h and air flow rate exceeds 57 kg/h. Ambient air with high temperature and relative humidity as well as the high salinity of the solution will slightly degrade the membrane flux.

Reversible C–H Activation in Zirconaaziridine Species: Characterization and Bonding of a Bridging (Amino)alkylidene Complex Active in Alkyne Hydroaminoalkylation

Efforts to synthesize a low-coordinate zirconaaziridine complex supported by a bis(ureate) ligand resulted in the formation of bridging aminoalkylidene 2. Complex 2 is a rare example of an aminoalkylidene complex featuring a μ(η2:η2)-N,C binding mode. This complex was fully characterized by single-crystal X-ray diffraction, NMR spectroscopy, and LIFDI-MS. Analysis of the natural localized molecular orbitals (NLMOs) showed a σ-bonding interaction between the alkylidene carbon and each zirconium center with significant delocalization of the Zr1–C1 σ bond into Zr2, thereby explaining the significant differences in the Zr–C bond lengths observed in the solid state. A solution-phase equilibrium between complex 2 and the putative zirconaaziridine species was supported by evaluating the reactivity of 2 in alkyne hydroaminoalkylation. The reaction of diphenylacetylene with complex 2 produced a five-membered metallacycle product, a key intermediate in alkyne hydroaminoalkylation. This reaction was greatly accelerated in the presence of pyridine, suggesting that the presence of neutral donors is essential to favor the formation of reactive zirconaaziridine complexes. In addition, the catalytic activity of complex 2 in the benchmark hydroaminoalkylation reaction of diphenylacetylene with N-benzylaniline was established.

The surface site interaction point approach to non-covalent interactions.

The functional properties of molecular systems are generally determined by the sum of many weak non-covalent interactions, and therefore methods for predicting the relative magnitudes of these interactions is fundamental to understanding the relationship between function and structure in chemistry, biology and materials science. This review focuses on the Surface Site Interaction Point (SSIP) approach which describes molecules as a set of points that capture the properties of all possible non-covalent interactions that the molecule might make with another molecule. The first half of the review focuses on the empirical non-covalent interaction parameters, α and β, and provides simple rules of thumb to estimate free energy changes for interactions between different types of functional group. These parameters have been used to have been used to establish a quantitative understanding of the role of solvent in solution phase equilibria, and to describe non-covalent interactions at the interface between macroscopic surfaces as well as in the solid state. The second half of the review focuses on a computational approach for obtaining SSIPs and applications in multi-component systems where many different interactions compete. Ab initio calculation of the Molecular Electrostatic Potential (MEP) surface is used to derive an SSIP description of a molecule, where each SSIP is assigned a value equivalent to the corresponding empirical parameter, α or β. By considering the free energies of all possible pairing interactions between all SSIPs in a molecular ensemble, it is possible to calculate the speciation of all intermolecular interactions and hence predict thermodynamic properties using the SSIMPLE algorithm. SSIPs have been used to describe both the solution phase and the solid state and provide accurate predictions of partition coefficients, solvent effects on association constants for formation of intermolecular complexes, and the probability of cocrystal formation. SSIPs represent a simple and intuitive tool for describing the relationship between chemical structure and non-covalent interactions with sufficient accuracy to understand and predict the properties of complex molecular ensembles without the need for computationally expensive simulations.

Convenient and accurate insight into solution-phase equilibria from FlowNMR titrations

Solution phase titrations are made easy by multi-nuclear FlowNMR spectroscopy with automated, continuous titre addition to give accurate insights into Brønsted acid/base, hydrogen bonding, Lewis acid/base and metal/ligand binding equilibria under native conditions.

A Modification of UNIQUAC Model for Electrolyte Solutions Based on the Local Composition Concept

In the present study, a thermodynamic model is developed to predict the phase equilibrium of electrolyte solutions. In this model the Pitzer–Debye–Huckel equation was used to calculate the long-range contribution of the activity coefficient. To take into account the short-rang part of activity coefficient a new modified UNIQUAC-based model was developed. The model was applied for 18 binary electrolyte solutions. Results show that the model presented reproduces the osmotic coefficients of electrolyte solutions accurately to high concentration levels of salt. Comparison of standard deviation of the model and E-NRTL and E-UNIQUAC-NRF models was performed in the manuscript.

Multiphase Behavior of Tetraphenylethylene Derivatives with Different Polarities at High Pressures.

Although both pressure and temperature are essential parameters governing thermodynamics, the effects of the pressure on solution-phase equilibria have not been well studied compared to those of temperature. Here, we demonstrate the interesting pressure-dependent behavior of tetraphenylethylene (TPE) derivatives in multiphase systems composed of an organic phase and an aqueous phase in the presence and absence of γ-cyclodextrin (γ-CD). In this system, tetraphenylethylene monocarboxylic acid (TPE1H) and its dicarboxylic acid (TPE2H2) are distributed in the aqueous phase and dissociated into the corresponding anions, that is, TPE1- and TPE22-, when the pH is sufficiently high. The distribution ratios of TPE1H/TPE1- and TPE2H/TPE22- show opposing pressure dependencies: the distribution of the former in the organic phase increases with increasing pressure, whereas that of the latter decreases. The 1:1 complexation constants of TPE1- and TPE22- with γ-CD, which can be determined from the distribution ratios in the presence of γ-CD, also show opposing pressure dependencies: the former shows a positive pressure dependence, but the latter exhibits a negative one. These pressure effects on the distribution and complexation of TPE derivatives can be interpreted based on the differences in the molecular polarity of these solutes. The water permittivity is enhanced at high pressure, thus stabilizing the more polar TPE22- in the aqueous phase to a larger extent than TPE1- and, as a result, reducing its distribution in the organic phase, as well as its complexation with γ-CD. Fluorescence spectra in the aqueous phase suggest that the TPE derivatives form aggregates with γ-CD molecules, as detected by the specific fluorescence. In addition, the fluorescence intensities of the γ-CD complexes are enhanced at high pressures because of the restricted rotation of the phenyl rings in the TPE molecules. This study provides new perspectives for multiphase partitioning and an attractive alternative to conventional extraction methods.

Predicting phase equilibrium of aqueous sugar solutions and industrial juices using COSMO-SAC

COSMO-SAC model was used to predict bubble point pressure, bubble point temperature, water activity, freezing point depression and solubility of sugars in aqueous solutions. COSMO-SAC is based on quantum chemistry computations and has a high predictive character, not requiring a specific parameter calibration for each application. For most systems studied, the results obtained were close to experimental data, with relative mean errors varying from 0.1% to 6.4% for vapor–liquid equilibrium. Solubility results with COSMO-SAC presented the same tendency observed in experimental data, but with higher deviations, probably due to the fact that the loss of crystalline structure in sugars is a kinetic process more than a thermodynamic melting, and does not occur at a single temperature with a constant enthalpy value. COSMO-SAC model was also used to predict industrial juices water activity, bubble point temperature, and freezing point depression. Very low deviations from experimental data were observed for COSMO-SAC calculations, similar to those found for simpler sugar solutions.

Measurement, correlation and modelling of high-pressure phase equilibrium of PLGA solutions in CO2

Poly (lactic-co-glycolic acid) (PLGA) is a copolymer used as drug carrier in controlled release systems as microparticles or scaffolds. Foamed structures are industrially obtained by injecting gas at temperatures above the melting point of the polymer that may promote PLGA degradation. High temperatures are avoidable in this foaming process if a polymer dissolution is used. Ethyl acetate and ethyl lactate are suitable solvents for the PLGA since the polymer is easily solubilised, is environmentally friendly and highly recommendable for medical purposes. CO2 is proposed as antisolvent because is environmentally benign, non-flammable and non-toxic. The knowledge of the solubility of these solvents in CO2 is essential to find the most appropriate working conditions for the foaming process. In this work, the solubility of ethyl acetate and ethyl lactate in CO2 in the presence of different initial concentrations of PLGA has been studied at 298.15 K and at pressures up to 150 bar using a high-pressure variable volume view cell.

Thermodynamic analysis of phase equilibrium and surface tension of ternary polymer solutions

AbstractThe liquid–liquid equilibrium (LLE) and surface behavior of polymer solutions were investigated. Systems of poly vinyl methyl ether (PVME)/water and polystyrene (PS)/cyclohexane were chosen as model systems because they show different types of LLE and surface behavior. Ternary polymer solutions of PVME/water/alcohol and PS/cyclohexane/alcohol were also studied. The cloud points of given systems were determined by thermo‐optical analysis method. For surface tension measurements at the air/polymer solution interface, the well‐known plate method was utilized. The investigated polymer solutions exhibit various types of LLE and surface behavior depending on the type of solvent and temperature. The modified double lattice model with chain length dependence is used for description of the phase equilibrium. To improve the interpretation of the surface behavior of the polymer solution, we developed a new thermodynamic frame work based on density gradient theory. Thermodynamic analysis was also conducted using the proposed model to provide understanding of the surface behavior. The surface energy difference and interchange energy had an important role in the driving force of the surface behavior. Utilizing the predetermined model parameters from the phase equilibrium calculation, the proposed model provides satisfactory agreement with measured surface tension data, with less than 5% error.

Single Cell Titration-Type Assay for Plasma Membrane Cholesterol Chemical Potential.

In this paper, a titration-type assay is described that determines the minimum concentration of cholesterol in solution that is required to drive net influx of cholesterol to the plasma membrane and thus increase the cholesterol concentration. The increase in cholesterol in the plasma membrane is detected by cholesterol diffusion at the site of contact by a cholesterol oxidase-modified microelectrode. In the presented thermodynamic model, the minimum solution phase cholesterol concentration that drives influx to the plasma membrane is a close approximation of the true solution-phase equilibrium concentration of cholesterol produced from cellular cholesterol efflux and as such it is a quantitative measure of the chemical potential of cholesterol in the cellular plasma membrane. This assay provides a measure of cholesterol chemical potential in the living cellular plasma membrane through reference to a solution concentration which avoids invoking classic kinetic theory to relate a rate to a specific thermodynamic activity and which avoids uncertainty associated with mass transfer phenomena.

Insight into thermal, crystallization kinetics, and phase behaviors of palm kernel oil and its olein/stearin by differential scanning calorimetry

ABSTRACTThe fractionation of oils has received considerable research attention, aiming at the modification of the properties of oils. The thermal and crystallization properties of palm kernel oil (PKO) and its olein/stearin (PKOL/PKST) were systematically investigated using differential scanning calorimetry (DSC). Based on the isothermal DSC results, crystallization temperature exerted critical effect on co-crystallization of PKOL and PKST. Moreover, it is reported that PKOL could be further separated by controlling the crystallization temperature, while PKST is hard to be further separated. The PKOL/PKST mixtures with different compositions were prepared and subjected to dynamic DSC analysis. The results illustrated that PKO meets the phase equilibrium of quasi-solid solutions.

Phase Equilibrium and Interfacial Tension of Binary and Ternary Polymer Solutions

The liquid–liquid equilibrium (LLE) and interfacial tensions of binary and ternary polymer solutions of polystyrene in cyclohexane and methylcyclohexane are investigated. The chain length dependent modified double lattice model (MDL-CL) is applied to describe experimental phase diagrams measured by thermo-optical analysis. The proposed model is also combined with the modified density gradient theory to calculate interfacial tension between two coexisting liquid phases of the investigated systems. The calculated results of LLE and interfacial tensions using the MDL-CL model combined with the modified density gradient theory show good agreement with experimental data. The interfacial tension of the ternary system (polystyrene + cyclohexane + methylcyclohexane) is described with the parameters obtained from the binary subsystems (polystyrene + cyclohexane and polystyrene + methylcyclohexane). A comparison of experimental and theoretical phase behaviors and interfacial tensions demonstrates that the theoretic...

Relationship between Individual and Competitive Adsorption Isotherms on Molecularly Imprinted Polymers

Molecularly imprinted polymers (MIP) are a new generation of selective adsorbents. In practical applications of MIPs simultaneous adsorption of at least two compounds occurs. Simultaneous (typically competitive) adsorption on MIPs has not yet been quantitatively analyzed. This paper shows that with a typical type of MIP the individual isotherms of two compounds coincide with their competitive isotherms in the logD-logq isotherm plot, where D is the distribution coefficient and q is the adsorbed concentration. Based on this observation the usual competitive isotherm, i.e., the (c 1 ,c 2 ) to (q 1 ,q 2 ) mapping can be established from the two individual isotherms. (The c-s are the respective solution phase equilibrium concentrations.) Batch separation experiments can be easily designed and the selectivity of the MIPs is also easily determined without the tedious measurement of the full competitive isotherm.

Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations.

Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein–ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein–ligand complex over free protein and minimize the protein–ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein–ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5′-guanosine monophosphate (GMP) and 5′-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.Graphical ᅟElectronic supplementary materialThe online version of this article (doi:10.1007/s13361-016-1417-x) contains supplementary material, which is available to authorized users.

Effects of polydispersity on liquid–liquid equilibrium of polymeric fluids

The effects of polymer polydispersity on the liquid–liquid equilibrium (LLE) of polymer solutions were investigated for the simple case of polydisperse polymer solutions: mixtures composed of a solvent and two monodisperse polymers of different molecular weights. Various quasi-binary cloud point curves including the upper critical solution temperature (UCST), lower critical solution temperature (LCST), both UCST and LCST, and closed loop miscibility were determined from thermal optical analysis (TOA). To describe the phase equilibrium of polydisperse polymer solutions, we extended the chain length contribution term in the modified double lattice chain length dependent model (extended MDL-CL). Phase equilibrium calculations were conducted for several ternary systems including hypothetical hourglass type LLE. The extended MDL-CL model appropriately described the effect of polymer polydispersity on the LLE of polymer solutions and the calculated results were in satisfactory agreement with the experimental data.

Non-equilibrium reaction and relaxation dynamics in a strongly interacting explicit solvent: F + CD3CN treated with a parallel multi-state EVB model.

We describe a parallelized linear-scaling computational framework developed to implement arbitrarily large multi-state empirical valence bond (MS-EVB) calculations within CHARMM and TINKER. Forces are obtained using the Hellmann-Feynman relationship, giving continuous gradients, and good energy conservation. Utilizing multi-dimensional Gaussian coupling elements fit to explicitly correlated coupled cluster theory, we built a 64-state MS-EVB model designed to study the F + CD3CN → DF + CD2CN reaction in CD3CN solvent (recently reported in Dunning et al. [Science 347(6221), 530 (2015)]). This approach allows us to build a reactive potential energy surface whose balanced accuracy and efficiency considerably surpass what we could achieve otherwise. We ran molecular dynamics simulations to examine a range of observables which follow in the wake of the reactive event: energy deposition in the nascent reaction products, vibrational relaxation rates of excited DF in CD3CN solvent, equilibrium power spectra of DF in CD3CN, and time dependent spectral shifts associated with relaxation of the nascent DF. Many of our results are in good agreement with time-resolved experimental observations, providing evidence for the accuracy of our MS-EVB framework in treating both the solute and solute/solvent interactions. The simulations provide additional insight into the dynamics at sub-picosecond time scales that are difficult to resolve experimentally. In particular, the simulations show that (immediately following deuterium abstraction) the nascent DF finds itself in a non-equilibrium regime in two different respects: (1) it is highly vibrationally excited, with ∼23 kcal mol(-1) localized in the stretch and (2) its post-reaction solvation environment, in which it is not yet hydrogen-bonded to CD3CN solvent molecules, is intermediate between the non-interacting gas-phase limit and the solution-phase equilibrium limit. Vibrational relaxation of the nascent DF results in a spectral blue shift, while relaxation of the post-reaction solvation environment results in a red shift. These two competing effects mean that the post-reaction relaxation profile is distinct from what is observed when Franck-Condon vibrational excitation of DF occurs within a microsolvation environment initially at equilibrium. Our conclusions, along with the theoretical and parallel software framework presented in this paper, should be more broadly applicable to a range of complex reactive systems.

Phase liquid-vapor equilibria and thermodynamic properties of solutions of n-propanol-aliphatic ketones

The boiling points of solutions of five binary systems are measured using the ebulliometric method in the pressure range of 4.4–101.3 kPa. Compositions of the equilibrium vapor phases of systems are calculated, based on the constructed pressure isotherms of saturated vapor. The values of excess Gibbs energy and the enthalpy and entropy of solutions are calculated from the data on the liquid-vapor equilibrium. The patterns of change in the phase equilibria and thermodynamic properties of the solutions are established, based on the composition and temperature of the systems. The liquid-vapor equilibrium of systems is described using the equations of Wilson and the NRTL (Non-Random Two-Liquid model).

Experimental measurement and thermodynamic modelling of phase equilibria of semi-clathrate hydrates of (CO2 + tetra-n-butyl-ammonium bromide) aqueous solution

Comprehensive studies on semi-clathrate hydrates phase equilibria are still required to better understand characteristics of this type of clathrates. In this communication, new experimental data on the dissociation conditions of semi-clathrate hydrates of {carbon dioxide+tetra-n-butyl-ammonium bromide (TBAB)} aqueous solution are first reported in a wide range of TBAB concentrations and at different pressures and temperatures. A thermodynamic model is then proposed to predict the dissociation conditions of the semi-clathrate hydrates for the latter system. The (hydrate+TBAB) aqueous solution (H+Lw) phase equilibrium prediction is considered based on Gibbs free energy minimization approach. A modified van der Waals–Platteeuw solid solution theory developed based on the (H+Lw) equilibrium information is employed to predict the dissociation conditions of semi-clathrate hydrates of carbon dioxide+TBAB. The properties of the aqueous solution are estimated using the AMSA-NRTL electrolyte model (considering the association and hydration of ions). The Peng–Robinson equation of state is used for estimating the gas/vapour phase properties. Results show that the proposed model satisfactorily predicts the experimental values with an average absolute relative deviation of approximately 13%.