Gibbs Free Energies Of Transfer Research Articles

Prediction of the bubble point pressure for the binary mixture of ethanol and 1,1,1,2,3,3,3-heptafluoropropane from Gibbs ensemble Monte Carlo simulations using the TraPPE force field

Configurational-bias Monte Carlo simulations in the Gibbs ensemble using the TraPPE force field were carried out to predict the pressure–composition diagrams for the binary mixture of ethanol and 1,1,1,2,3,3,3-heptafluoropropane at 283.17 and 343.13 K. A new approach is introduced that allows one to scale predictions at one temperature based on the differences in Gibbs free energies of transfer between experiment and simulation obtained at another temperature. A detailed analysis of the molecular structure and hydrogen bonding for this fluid mixture is provided.

Solvation of Ions in Aqueous Hydrophilic Polymer Solutions

We indicated, in our previous work, that tetraethylammonium (Et4N+) ion is solvated in an aqueous polymer solution in a similar fashion to in water, and the Et4N+ electrode can be used for a reference for the determination of transfer thermodynamic values. On the basis of this finding, we have evaluated the Gibbs free energy of transfer of selected ions from water to aqueous hydrophilic polymer solutions such as poly (ethylene glycol) and poly (acrylic acid) . X-ray absorption fine structure (XAF) measurements have allowed us to discuss the structural aspects of ions in the aqueous polymer solutions.

Investigation of aqueous biphasic systems formed from solutions of chaotropic salts with kosmotropic salts (salt–salt ABS)

A study of salt–salt aqueous biphasic systems (ABS) was conducted to increase our understanding of solutions of kosmotropic vs. chaotropic salts, especially since most ionic liquids (ILs) fall within the latter class. The salting-out strength of the kosmotropic salts follows the well established Hofmeister series, as observed in polymer–salt ABS, and can be directly related to the ions' Gibbs free energies of hydration (ΔGhyd). Most currently studied ILs are designed to have chaotropic cations and are thus salted-out by kosmotropic salts. Here, we describe the phase diagrams for imidazolium-, pyridium-, and quaternary ammonium- and phosphonium-based chloride salts (all chaotropic salts) salted-out by K3PO4, K2HPO4, K2CO3, KOH, and (NH4)2SO4 (all kosmotropic salts). The Gibbs free energy of methylene transfer (ΔGCH2) was also determined for 1-butyl-3-methylimidazolium chloride ([C4mim]Cl)/K3PO4, K2HPO4, and K2CO3 ABS. The latter results are in the range of an ethanol–water to a chloroform–water system, and can be controlled predominately by the system composition.

Physicochemical Characterization and Dissolution Study of Solid Dispersions of Lovastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to‐carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Lovastatin compared with tablets containing Lovastatin without PEG or PVP.

Temperature and salt addition effects on the solubility behaviour of some phenolic compounds in water

Solubility-temperature dependence data for six phenolic compounds (PhC), contained in olive mill wastewater (OMWW), in water and in some chloride salts (KCl, NaCl, and LiCl) aqueous solutions have been presented and solution standard molar enthalpies (Δ sol H ∘) were determined using Van’t Hoff plots. The temperature was varied from 293.15 K to 318.15 K. Solubility data were estimated using a thermostated reactor and HPLC analysis. It has been observed that solubility, in pure water and in aqueous chloride solutions, increases with increasing temperature. The salting-out LiCl > NaCl > KCl order obtained at 298.15 K is confirmed. Results were interpreted in terms of the salt hydration shells and the ability of the solute to form hydrogen-bond with water. The standard molar Gibbs free energies of transfer of PhC (Δ tr G ∘) from pure water to aqueous solutions of the chloride salts have been calculated from the solubility data. In order to estimate the contribution of enthalpic and entropic terms, standard molar enthalpies (Δ tr H ∘) and entropies (Δ tr S ∘) of transfer have also been calculated. The decrease in solubility is correlated to the positive Δ tr G ∘ value which is mainly of enthalpic origin.

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire® 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol® F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed A L type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug–poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Solvation of Ions in Hydrophilic Layer of Polyoxyethylated Nonionic Micelle. Cooperative Approach by Electrophoresis and Ion-Transfer Voltammetry

Electrophoretic measurements of micellar mobility have revealed that polyoxyethylated nonionic surfactant micelles have negative zeta potential in various electrolytes, indicating that the partition of anions into the micelle dominates the entire electrolyte partition and the induced surface potential of the micelle. Although an excess of a negative charge is thus revealed in the micelle, it is uncertain whether anions are preferably solvated in the micelles or cations are expelled from the micelles. To determine the solvation energies of single ions in the hydrophilic layer of the micelle, we have performed ion transfer voltammetric measurements at microinterfaces between nitrobenzene and aqueous tetraethyleneglycol solution, which acts as a model for the palisade layer of the micelles. The cooperative utilization of these different methods has allowed us to determine the Gibbs free energy of transfer of a single ion without an extrathermodynamic assumption. On the basis of the resulting values, the partition of ions and the zeta potential induced by the imbalance of anionic and cationic partition have been quantitatively explained.

Retention in gas–liquid chromatography with a polyethylene oxide stationary phase: Molecular simulation and experiment

Configurational-bias Monte Carlo simulations in the isobaric–isothermal Gibbs ensemble were carried out to investigate the partitioning of normal alkanes, primary and secondary alcohols, symmetric alkyl ethers and arenes between a helium vapor phase and a polyethylene oxide stationary phase ( M W = 382 g mol −1). The united-atom version of the transferable potentials for phase equilibria force field was used to model all solutes, polyethylene oxide and helium. The Gibbs free energies of transfer and Kovats retention indices of the solutes were calculated directly from the partition constants at two different temperatures, 353 and 393 K. Chromatographic experiments on a Carbowax 20M retentive phase were performed for the same set of solutes and temperatures ranging from 333 to 413 K. The predicted retention indices for alcohols, ethers and arenes are overestimated by about 120, 70 and 20 retention index units, respectively, pointing to an overestimation of the first-order electrostatic interactions in the model system. Molecular-level analysis shows that hydrogen-bonding and dipole–dipole interactions lead to orientational ordering for the alcohol and ether analytes, whereas the weaker dipole–quadrupole interactions for the arene solutes are not sufficient to induce orientational ordering. The retention indices of alcohols and ethers decrease with increasing temperature because of the large entropic cost of hydrogen-bonding and orientational ordering. In contrast, the retention indices for arenes increase with increasing temperature because the entropic cost of cavity formation is smaller for arenes than for comparable alkanes.

Phase behavior of fatty acid/oil/water systems: Effect of the alkyl length chain acid

AbstractThe phase behavior of different fatty acids (FA) in pseudo‐ternary mixtures [(water)/(FA) + (alcohol)/(oil)] was studied. The Winsor I‐III‐II transitions of ionized compounds were attained by varying the FA composition through the formulation scan. The middle‐phase volume, the pH of the optimum system, and the partition coefficient increased with the chain length of FA. Conversely, the acid partition coefficient allows calculation of the Gibbs free energy of transfer of a CH2 group from oil to water, which is found to be +0.87 J/mol.

Efficient molecular simulations for environmentally benign processes

An efficient sampling technique namely the Hammersley sequence sampling (HSS) technique based on quasi-random numbers is applied to molecular simulations to increase computational efficiency and reduce the error in property calculations for efficient and environmentally friendly product and process design. Due to its k-dimensional uniformity properties, this sampling technique reduces the computational intensity and converges faster as compared to conventional Monte Carlo (MC) method based on pseudo-random numbers. Two case studies are presented in order to show the effect of the sampling technique on molecular simulations. The first case study involves the computation of equation of state (EOS) for a Lennard Jones fluid and the second case study concerns the prediction of Gibbs free energies of transfer for the calculation of octanol–water partition coefficients. The results show that the HSS technique provides about 3-fold gain in efficiency and reduces the number of cycles required to reach equilibration. Furthermore, the errors in property calculations are reduced for both of the case studies.

Direct calculation of Henry’s law constants from Gibbs ensemble Monte Carlo simulations: nitrogen, oxygen, carbon dioxide and methane in ethanol

Configurational-bias Monte Carlo simulations in the Gibbs ensemble were used to calculate Henry’s law constants, Ostwald solubilities, and Gibbs free energies of transfer for oxygen, nitrogen, methane, and carbon dioxide in ethanol at 323 and 373 K. These three solubility descriptors can be expressed as functions of mechanical properties that are directly observable in the Gibbs ensemble approach, thereby allowing for very precise determination of the descriptors. Additionally, the Henry’s law constants of multiple solutes can be computed from a single simulation. Most of the simulations were carried out for systems containing 1,000 solvent and up to 8 solute molecules, and further simulations using either 500 or 2,000 solvent molecules point to negligible system size effects. A comparison with experimental data shows that the united-atom version of the transferable potential for phase equilibria force field yields Henry’s law constants that reproduce well the differences between the four solutes and the changes upon increase of the temperature.

Bioavailability Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine, a Polyhydroxy Base, as a Novel Ternary Component

The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-β-cyclodextrin (HPβCD). The molecular inclusion of DRF-4367 with HPβCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPβCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubility enhancement were investigated by using phase solubility and thermodynamic parameters. The complexation of DRF-4367 with HPβCD is thermodynamically favored because the Gibbs free energies of transfer of the drug to the cyclodextrin cavity are negative. The solubilization efficiency and stability were further improved while retaining the favorable Gibbs free energies of transfer with the addition of meglumine. Inclusion ternary complex of DRF-4367 with HPβCD and meglumine showed significant improvement in dissolution compared with uncomplexed drug and binary system. Moreover, the phenomena of reprecipitation observed with binary system during dissolution could be avoided with meglumine as an enabling ternary component. This improved physicochemical behavior of ternary complex with the novel inclusion of a polyhydroxy base translated into an enhanced oral bioavailability of DRF-4367 compared with either uncomplexed drug or nanosuspension.

Enhancement of aqueous solubility of itraconazole by complexation with cyclodextrins using supercritical carbon dioxide

The formation of inclusion complexes between itraconazole, a highly hydrophobic drug, and α-, β-, γ-, and hydroxylpropyl-β-cyclodextrin (HP-β-CD) were assessed using phase-solubility techniques. The solubility of itraconazole increased as a function of cyclodextrin concentration showing an AL phase diagram indicating the formation of soluble complexes with 1:1 stoichiometry. The Gibbs free energies of transfer of the drug from aqueous solution to the cavity of cyclodextrin are negative and increase in magnitude with increasing cyclodextrin concentration. The solubility of itraconazole, as well as the stability constant of its complex with HP-β-CD, are found to be affected by the pH of the medium. The HP-β-CD cavity was found to have a greater affinity for the unionized itraconazole than the protonated one. It was found that the interaction between the drug and the cyclodextrin is weakened as the medium becomes more apolar by the addition of methanol. Also, the size of the cavity of the cyclodextrins plays an important role in the association process. Furthermore, the thermodynamic parameters of the complexation process were calculated, by monitoring the isothermic solubility diagrams of itraconazole–HP-β-CD and itraconazole–β-CD at various temperatures, to gain information on the driving forces for the formation of inclusion complexes. Drug formulations of itraconazole were prepared by complexation of the drug into different cyclodextrins using supercritical carbon dioxide in a static mode. The effects of cyclodextrins on the prepared inclusion complexes were studied and characterized by differential scanning calorimetry.Key words: cyclodextrin, itraconazole, inclusion complex, solubility, stability constant.

Electroactivity of redox-inactive proteins at liquid|liquid interface

We report on an observation of electroactivity of redox-inactive proteins at liquid|liquid interface. Since except for small polypeptide protamine, using ‘classic’ four-electrode setup it is impossible to facilitate a transfer of proteins across liquid|liquid interface, to observe protein electroactivity a carbon electrode shielded with thin layer of organic solvent was taken. Voltammograms of such shielded electrodes are sensitive to thermodynamics of anion re-solvation. To decrease Gibbs free energy of protein transfer from water to organic phase, and, thus, to record protein electroactivity at liquid|liquid interface, the reversed micelles of surfactants able to solubilise proteins in organic solvent were formed. Varying proteins and surfactants, as well as polarity of organic solvent, we proved that the observed raise in current of shielded electrodes, which in certain cases exceeds background by the two orders of magnitude, is indeed provided by the presence of proteins. Analytical parameters of shielded electrode are dependent on protein molecular weight and its interfacial properties. Electroactivity of redox-inactive proteins registered at liquid|liquid interface gives promise for wide application of electroanalytical chemistry in proteomics.

Ion-Association Analysis between Inorganic Anions and Symmetrical Tetraalkylammonium Ions in Aqueous-Acetonitrile Media by Capillary Zone Electrophoresis

Abstract Weak ion-association equilibrium was analyzed in a water-acetonitrile solution at 25 °C by capillary zone electrophoresis using an ordinary silica capillary. The ion associates examined were formed between some inorganic anions and symmetrical tetraalkylammonium ions, where a series of acetonitrile compositions up to 62.2% (m/m) were investigated. Ion-association constants, Kass, were determined by analyzing the changes in the electrophoretic mobility; the Kass values for most of the anions increased up to about 47% (m/m) acetonitrile, beyond which they remained constant, or decreased slightly. The ion-association equilibrium between tetramethylammonium and bromide ions in aqueous-acetonitrile and in aqueous-ethanol media were compared through the Gibbs free energy of transfer, which revealed that the extent of the equilibrium in aqueous-acetonitrile media is dependent mainly on the increasing instability of Br−. On the other hand, those in aqueous-ethanol media depend on the instabilities of both tetramethylammonium and bromide ions.

Temperature Dependence of Hydrogen Bonding: An Investigation of the Retention of Primary and Secondary Alcohols in Gas−Liquid Chromatography

Configurational-bias Monte Carlo simulations in the Gibbs Ensemble were carried out to investigate the analyte partitioning of n-pentane, n-hexane, n-heptane, 1-propanol, and 2-propanol into a dioctyl ether retentive (stationary) phase used in gas-liquid chromatography. The united-atom version of the TraPPE (transferable potentials for phase equilibria) force field was used to model all analytes and the solvent. The analyte partition coefficients, Gibbs free energies of transfer, and Kovats retention indexes were calculated at four different temperatures ranging from 303.15 to 348.15 K. Although hydrogen bonding is a major contributor to the retention of the alcohol analytes over the entire temperature range, its importance for the separation factor between the primary and secondary alcohol decreases substantially with increasing temperature. The enthalpies and entropies for hydrogen bond formation were also estimated from the temperature dependence of the corresponding equilibrium constants. In agreement with experimental measurements, it is observed that the hydrogen bond involving 1-propanol is enthalpically favored, but entropically disfavored compared to 2-propanol.

Non-linear Effects of Temperature and Urea on the Thermodynamics and Kinetics of Folding and Unfolding of Hisactophilin

Extensive measurements and analysis of thermodynamic stability and kinetics of urea-induced unfolding and folding of hisactophilin are reported for 5-50 degrees C, at pH 6.7. Under these conditions hisactophilin has moderate thermodynamic stability, and equilibrium and kinetic data are well fit by a two-state transition between the native and the denatured states. Equilibrium and kinetic m values decrease with increasing temperature, and decrease with increasing denaturant concentration. The betaF values at different temperatures and urea concentrations are quite constant, however, at about 0.7. This suggests that the transition state for hisactophilin unfolding is native-like and changes little with changing solution conditions, consistent with a narrow free energy profile for the transition state. The activation enthalpy and entropy of unfolding are unusually low for hisactophilin, as is also the case for the corresponding equilibrium parameters. Conventional Arrhenius and Eyring plots for both folding and unfolding are markedly non-linear, but these plots become linear for constant DeltaG/T contours. The Gibbs free energy changes for structural changes in hisactophilin have a non-linear denaturant dependence that is comparable to non-linearities observed for many other proteins. These non-linearities can be fit for many proteins using a variation of the Tanford model, incorporating empirical quadratic denaturant dependencies for Gibbs free energies of transfer of amino acid constituents from water to urea, and changes in fractional solvent accessible surface area of protein constituents based on the known protein structures. Noteworthy exceptions that are not well fit include amyloidogenic proteins and large proteins, which may form intermediates. The model is easily implemented and should be widely applicable to analysis of urea-induced structural transitions in proteins.

Thermodynamic properties of hydrochloric acid in mixed solvents HCl(mA)+NaCl(mB) in (1−x)H2O+xD-fructose at T=(278.15 to 318.15) K

The thermodynamic properties of system (HCl + NaCl + C6H12O6 + H2O) were studied by e.m.f. measurement in the cells without liquid junction: (A)Pt,H2(p=101.325kPa)|HCl(0.01000mol·kg-1)|AgCl–Ag (B)Pt,H2(p=101.325kPa)|HCl(m),C6H12O6(w),H2O(1-w)|AgCl–Ag (C)Pt,H2(p=101.325kPa)|HCl(mA),NaCl(mB),C6H12O6(w),H2O(1-w)|AgCl–Ag At constant total ionic strength (0.5, 1.0, 1.5, and 2.0) mol · kg−1, from (5 to 45) °C, where mA and mB are the molalities of HCl and NaCl, respectively, and w is the mass fraction of fructose in the mixed solvent, which is w = 0.1 during all the measurements. The standard electrode potential of Ag|AgCl in the pure water and mixed solvent has been determined from cells (A), (B). The activity coefficients lg γA of HCl in the mixed solvent system have been determined from cell (C).The results show that the activity coefficients of HCl in (HCl + NaCl) solutions still obey Harned’s Rule. The standard transfer Gibbs free energies, entropy and enthalpy of HCl have been calculated. The primary, secondary and total medium effect of HCl have been calculated and discussed.

Thermodynamic properties of hydrochloric acid in mixed solvents: {HCl( mA) + NaCl( mB)} in {(1 − x)H 2O + xd-fructose} at T = (278.15 to 318.15) K

The thermodynamic properties of system (HCl + NaCl + C 6H 12O 6 + H 2O) were studied by e.m.f. measurement in the cells without liquid junction: (A) Pt , H 2 ( p = 101.325 kPa ) | HCl ( 0.01000 mol · kg - 1 ) | AgCl – Ag (B) Pt , H 2 ( p = 101.325 kPa ) | HCl ( m ) , C 6 H 12 O 6 ( w ) , H 2 O ( 1 - w ) | AgCl – Ag (C) Pt , H 2 ( p = 101.325 kPa ) | HCl ( m A ) , NaCl ( m B ) , C 6 H 12 O 6 ( w ) , H 2 O ( 1 - w ) | AgCl – Ag At constant total ionic strength (0.5, 1.0, 1.5, and 2.0) mol · kg −1, from (5 to 45) °C, where m A and m B are the molalities of HCl and NaCl, respectively, and w is the mass fraction of fructose in the mixed solvent, which is w = 0.1 during all the measurements. The standard electrode potential of Ag | AgCl in the pure water and mixed solvent has been determined from cells (A) and (B). The activity coefficients lg γ A of HCl in the mixed solvent system have been determined from cell (C).The results show that the activity coefficients of HCl in (HCl + NaCl) solutions still obey Harned’s Rule. The standard transfer Gibbs free energies, entropy and enthalpy of HCl have been calculated. The primary, secondary and total medium effect of HCl have been calculated and discussed.

An Investigation of Weak Ion Association Equilibria between Inorganic Anions and Tetraalkylammonium Ions in Ethanol–Aqueous Media Using Capillary Zone Electrophoresis

Abstract Weak ion association equilibria between inorganic anions, ranging in charge from −1 to −4, and symmetrical tetraalkylammonium ions, R4N+ (R = Me, Et, Pr, Bu, n-Am), were investigated in formate buffer solutions containing a variable composition of ethanol (0–62.9% (m/m)). The individual effective mobilities of the inorganic anions in a series of tetraalkylammonium chloride solutions were measured using an ordinary silica capillary maintained at 25.0 ± 0.1 °C under a negative potential (−10 kV) and direct UV detection (λ = 220 nm). Under the stated experimental conditions, the association constants, Kass, showed a modest increase as the amount of ethanol in the buffer was increased. The concepts of medium effect and Gibbs free energy of transfer were applied to weak ion equilibria in order to investigate changes in association constant as the ethanol content in the buffer solutions was increased. The above treatment on selected associations revealed that the increased instability of the inorganic anion in mixed ethanolic solutions is responsible for the observed increase in Kass.