Preferential Solvation Parameters Research Articles

Solubility of atenolol in aqueous propylene glycol mixtures revisited: IKBI preferential solvation analysis

ABSTRACT The preferential solvation parameters of atenolol in aqueous binary mixtures of propylene glycol (PG) were derived from reported molar solubility values after conversion to mole fractions by using the inverse Kirkwood–Buff integrals method. This drug is sensitive to preferential solvation effects in this binary system. The preferential solvation parameter by PG (δx 1,3) is negative in water-rich mixtures but positive in mixtures of 0.20 < x 1 < 1.00. It is conjecturable that hydrophobic hydration around the non-polar methyl and phenylene groups of this drug observable in water-rich mixtures could play a relevant role in drug solvation. Otherwise, in mixtures of 0.20 < x 1 < 1.00, the preferential solvation by PG could be due to the acidic behaviour of atenolol.

The Preferential Solvation of Methyl Red in Various Binary Aqueous Solutions: Solvatochromism, Preferential Solvation Parameters, Microheterogeneity of Solvents and Polarity Scale.

The solvatochromic characteristics of methyl red were examined in several aqueous solutions from pure water, with methanol, ethanol, propanol, acetonitrile, and dioxane. In order to explain the preferred solvation of the probe azo dye in the binary mixed solvents, the solvent exchange model of Bosch and Roses was used to evaluate the association between the empirical solvent polarity scale (ET) values of MR and solvent composition. Non-linear solvatochromism of methyl red was noted in all aqueous mixtures containing methanol, ethanol, propanol, acetonitrile, and dioxane. In addition to calculating the local mole fraction of each solvent composition in the cybotactic area of the probe, the impact of the solvating shell composition on the preferential solvation of the solute dye was examined in terms of both solvent-solvent and solute-solvent interactions. The local mole fraction of each solvent composition in the cybotactic region of the probe was also calculated. The results indicated that the MR solvation shell was thoroughly saturated with the solvent complex S12 in the following order: dioxane > ethanol > methanol > acetonitrile > propanol. Data from the binary systems were analyzed with KAT parameters using a multi-model; in aqueous methanol and ethanol solutions, the hydrogen acidity was more responsible for the spectral shift, whereas in aqueous acetonitrile and dioxane solutions, the basicity has a greater influence.

Preferential Solvation in Binary Liquid Mixtures with Norbornadiene

Norbornadiene has been found useful in organic and polymer synthesis and recently its mixtures have been found useful in solar energy storage. Structure factors S(0) help to identify structure and binding at microscopic level and also play a significant role in understanding and characterizing exchanges in liquid systems. Preferential solvation Parameter δij provides information about deviation from ideal behavior for the solvent. In this work structure factors S(0) and preferential solvation Parameter δij were evaluated of binary Liquid Mixtures of Norbornadiene with Benzene, Cyclohexane, Decane, and Carbon Tetrachloride using Kirkwood Buff formalism. For the said binary mixtures experimental data pertaining to the calculations were taken from literature. Obtained results indicate that molecules which tend to form dipole interactions or hydrogen bonds form favorable interactions as seen in Norbornadiene + carbon tetrachloride where the small molecule of CCl4 is not sterically hindered to approach the polar Norbornadiene molecule. Long chain and ring structure of carbon have a negative influence on hetero interactions. Studying these parameters will develop predictive techniques to determine the right composition for optimum performance of the liquid mixture.

Prediction of cosolvent effect on solvation free energies and analysis of intermolecular forces of tizanidine hydrochloride in ethyl acetate + methanol / ethanol mixtures

The solubility of small molecule drug in solvents can be dramatically affected by addition of a suitable cosolvent, which makes the screening of the best-suited cosolvent an important task for the purification and preparation. The present work aims to improve the fundamental understanding of tizanidine hydrochloride (TIZ HC) solvation by cosolvent. Solubility experimental data from TIZ HCl in mixtures of ethyl acetate + alcohols were obtained at different temperatures with the method of isothermal equilibrium. In the system of ethyl acetate + methanol, the solubility data increased firstly and then decreased with an increase in ethyl acetate content, however, the strictly monotonic decreasing of solubility in ethyl acetate + ethanol mixtures was observed. The solubility correlation fitting was performed with the Jouyban-Acree model and CNIBS/R-K model. The solvent effect analysis indicates that the hydrogen bond acidity, the polarity / polarizability and the cohesive forces of the solvent have a greater influence on the solubility, which was further validated by the local quantitative molecular surface analysis results of electrostatic potential (ESP). The dissolution process of TIZ HCl in systems with different solvent compositions was analyzed in the form of preferential solvation parameters, it was found that methanol is the preferred solvent in the solvation shell of TIZ HCl in methanol-rich and ethyl acetate-rich mixtures but the ethanol is preferred in intermediate compositions and ethyl acetate-rich mixtures. Moreover, the types of intermolecular solute–solvent interactions were discussed on the basis of the structural characteristics of TIZ HCl. The solvation free energy is a key parameter describing solvent effects, which is extremely important for understanding solution chemistry. For this part, with the aid of density functional theory (DFT) and molecular dynamics (MD) simulations, it was found that the cosolvent effect is consistent with the prediction trend of solvation free energy of TIZ HCl in each systems. The effect of the cavity formed by the solvent molecules and dipole moment of solute was calculated accordingly by the solvation model based on density (SMD) for explaining the former behavior.

Research on sulfenone in four aqueous cosolvent systems at (278.15–323.15) K: solubility, modelling, hansen solubility parameter, preferential solvation and thermodynamic properties

The equilibrium solubility of sulfenone in various aqueous cosolvent systems was determined by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. Four cosolvents (methanol, ethanol, isopropanol and n-propanol) exhibited different power in dissolving. The specific performance was that in the saturated state, the content of sulfenone in n-propanol + water was the most and in methanol + water was the least. The Jouyban-Acree (J-A), van’t Hoff-Jouyban-Acree (V-J-A) and Apelblat-Jouyban-Acree (A-J-A) models were utilized to correlate the obtained solubility data of sulfenone. The maximum of relative average deviation (RAD) and root-mean-square deviation (RMSD) were 1.47 × 10−2 (from A-J-A) and 6.07 × 10−5 (from V-J-A). In addition, the difference in dissolution was explained from a microscopic point of view through the acquisition of hansen solubility parameters (HSPs). The preferential solvation parameter δx1,3 was calculated by Inverse Kirkwood-Buff Integrals (IKBI) method, the change trend of δx1,3 presented in the entire concentration range was non-linear. The apparent thermodynamic parameters were calculated by van’t Hoff plots and the results indicated that the dissolution process of sulfenone is an endothermic and entropy increment process.

Study on 2-amino-4-chloro-6-methoxypyrimidine in four binary solvent mixtures: Solubility measurement, calculation, preferential solvation and extended Hildebrand solubility parameter approach analysis

Equilibrium mole fraction solubility of 2-amino-4-chloro-6-methoxypyrimidine in methanol/ethanol/acetone/N,N-Dimethylformamide (DMF) plus water was experimentally measured by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. The mixed solvents with low moisture and high temperature played a supportive role in the dissolution of 2-amino-4-chloro-6-methoxypyrimidine. The amount of 2-amino-4-chloro-6-methoxypyrimidine dissolved in DMF + water was more than that in other three systems and the ranges of values for the solubility (mole fraction) of 2-amino-4-chloro-6-methoxypyrimidine in methanol/ethanol/acetone/DMF + water were 0.0002046–0.009616, 0.0002046–0.01060, 0.0002046–0.04918 and 0.0002046–0.1197, respectively. The Jouyban-Acree (JA), Apelblat-Jouyban-Acree (AJA) and van’t Hoff-Jouyban-Acree (VJA) model were applied to calculate the solubility data of 2-amino-4-chloro-6-methoxypyrimidine in mixtures. The preferential solvation parameter δx1,3 > 0 in 0.32 < xmethanol < 1, 0.24 < xethanol < 1, 0.21 < xacetone < 1 and 0.19 < xDMF < 1, the 2-amino-4-chloro-6-methoxypyrimidine was preferentially dissolved by cosolvents and the 2-amino-4-chloro-6-methoxypyrimidine was dissolved preferentially by water within δx1,3 < 0. What’s more, the interaction between solute - solvent molecules and the internal interaction of molecules was analyzed by extend Hildebrand solubility approach (EHSA) and in the concentration range with W > δ1+2δ3, the hydrophobic groups in the 2-amino-4-chloro-6-methoxypyrimidine played a dominant role, while in other ranges self associations of solute, solvent or both were observed. The dissolution thermodynamic properties were obtained by van’t Hoff plots and the ranges of values for ΔsolHo (kJ∙mol−1)/ ΔsolGo (kJ∙mol−1)/ ΔsolSo (J∙mol−1) were 9.74 – 31.12, −17.84 – 4.96 and 33.79 – 161.89.

Solubility measurement of syringic acid, trans-cinnamic acid, p-coumaric acid, and vanillin constituent of Deverra DC. genus in (ethyl acetate + ethyl alcohol) mixtures: Thermodynamic modeling and preferential solvation

This work aims firstly to measure the solubility of four natural phenolic compounds (syringic acid, trans-cinnamic acid, p-coumaric acid, and vanillin) present in Deverra DC. Genus in (ethyl alcohol + ethyl acetate) using the gravimetric method from 283.15 to 323.15 K at normal pressure and then to analyze the solubility using the Jouyban-Acree and van't Hoff-Jouyban-Acree models. Secondly, based on the obtained solubility data, the preferential solvation parameters (δx1,3) of four natural phenolic compounds (PhC) in double solvent mixtures of ethyl alcohol (1) + ethyl acetate (2) were calculated using the inverse Kirkwood-Buff integrals method. The δx1,3 numbers differ indirectly with the co-solvent (1) fraction in all the binary mixtures. For the ethyl alcohol (1) + ethyl acetate (2) systems, the δx1,3 values are negative in ethyl acetate-rich mixtures and positive in constituents (x1) ranging from 0.59 to 1 for syringic acid, 0.51 to 0.63 trans-cinnamic acid, and 0.48 to 0.63 for vanillin in the mole fraction of ethyl alcohol. However, for the ethyl alcohol (1) + ethyl acetate (2) +p-coumaric acid (3) mixtures comprising 0 <x1 < 0.63, the values of δx1,3 are positive. This indicates that the co-solvent preferentially dissolved p-coumaric acid. The positive amounts of δx1,3 obtained are because the phenolic molecules that interact with the hydrogen acceptor groups existing in the co-solvent have higher acidic properties.

Equilibrium solubility, solvation and dissolution thermodynamics, and DFT study of 18β-glycyrrhetinic acid in solutions of 1,4-dioxane/N,N-dimethylformamide/ethanol/isopropanol + water

This study investigated the solubility, solvation behavior, dissolution thermodynamics, and intermolecular interactions of 18β-glycyrrhetinic acid (GA) in binary aqueous blends of 1,4-dioxane, N,N-dimethylformamide (DMF), ethanol and isopropanol. The solubility experiments were performed using the shake-flask technique at 101.0 kPa and temperatures ranging from 278.15 to 323.15 K. The lowest and highest GA solubility was observed in water and neat organic solvent, respectively. Experiments based on XRD analysis revealed no crystal transition or solvation. Modified van't Hoff–Jouyban–Acree and Jouyban–Acree models connected the solubility with relative average deviations (RAD) not exceeding 3.63 %. The extended Hildebrand solubility parameter method was utilized here to examine the equilibrium solubility at 298.15 K, yielding a RAD of 3.95 %. According to the linear solvation energy relationship examination, the dipolarity-polarizability and solubility parameter of solutions significantly influence the solubility variation. Using the inverse Kirkwood–Buff integrals, the preferential solvation of GA by organic solvents and water was investigated quantitatively. Positive preferential solvation parameter for organic solvents in rich and moderate organic solvent blends indicated that GA was preferentially solvated by the organic solvents. GA is a Lewis acid with respect to the cosolvent molecules. Thermodynamic investigation of dissolution characteristics and enthalpy–entropy compensation revealed an endothermic process and enthalpy-driven mechanism for dissolving GA in various blends. Finally, microscopic quantitative examination of molecular surface was used to highlight the electrostatic properties of acidity/basicity of GA. The –C = O, OH, and > COOH groups are the main targets of electrophilic and nucleophilic attack. The weak interactions between GA and solvent were visually examined using an independent gradient model based on Hirshfeld partition analysis.

Investigation on florasulam in aqueous blends including solubility, preferential solvation, thermodynamic properties and enthalpy–entropy compensation

The equilibrium solubility of florasulam in solvent mixtures (methanol/ethanol /n-propanol/propylene glycol (PG) + water) was determined experimentally by isothermal saturation method at 278.15 K to 323.15 K under 101.2 kPa. Both high temperature and low water content of solvent promoted the dissolution of florasulam. Under given conditions, the mole fraction of florasulam was greater in (n-propanol + water) than other three solvent mixtures. Besides, the solubility of florasulam was correlated with the Jouyban-Acree (J-A) model and van’t Hoff-Jouyban-Acree (V-J-A) model. The obtained average relative deviations (RAD) and root mean square deviations (RMSD) were no >4.04 % and 1.73 × 10-4. The calculated preferential solvation parameter δx1,3 was used to analyze the preferential dissolution of florasulam between water and alcohols from the molecular perspective. The result is that in the intervals 1 > xmethanol > 0.32, 1 > xethanol > 0.23 and 1 > xn-propanol > 0.19, the florasulam was preferentially dissolved by methanol/ethanol/n-propanol. In other concentration ranges, the florasulam was preferentially dissolved by water. The reason for the special existence of PG + water is that |δx1,3| < 1 × 10-2 and the dissolution of florasulam in it conformed to the uncertainty propagation rather than preferential solvation theory. The parameters (ΔsolHo, ΔsolGo, ΔsolSo, ΔtrGo, ΔtrHo and ΔtrSo) that could reflect the apparent and transfer thermodynamic properties were obtained. It was concluded that the solubility change of florasulam was dominated by entropy and the transfer of florasulam from pure water to mixtures was an exothermic process. Finally, the enthalpy–entropy compensation analysis further studied the mechanism of enthalpy and entropy in the dissolution process.

3,4,5-Trimethoxycinnamic acid in aqueous co-solvent solutions of isopropanol/acetone/methanol/ethanol: Solubility, preferential solvation and intermolecular interactions

Quantitative analysis of molecular surface was applied at the microscopic level to emphasize the electrostatic characteristics of acidity/basicity of 3,4,5-trimethoxycinnamic acid (TMCA). The primary sites of electrophilic and nucleophilic assault are the –C=O and >OH groups owing to global maximum and lowest electrostatic potentials of −155.5 kJmol−1 and +185.8 kJmol−1, respectively. Using the independent gradient model based on Hirshfeld partition analysis, the weak interactions between TMCA and solvent were visually inspected. The solubility of TMCA in four co-solvent blends, namely isopropanol + water, methanol + water, acetone + water and ethanol + water, was determined under 101.2 kPa by the isothermal shake-flask technique. As the temperature increased from 278.15 to 323.15 K, the TMCA solubility in neat methanol increased from 66.20 × 10−4 to 942.9 × 10−4; while in neat acetone, it increased from 175.1 × 10−4 to 555.1 × 10−4. Two solubility curves intersect at about 305.8 K. According to the research based on KAT- linear solvation energy relationships, the solvent–solvent interactions are mostly responsible for the solubility fluctuation. The relationship between solubility and experimental conditions was established using three models: the Jouyban–Acree model, the modified Wilson model, and the modified Jouyban–Acree-van't Hoff model, yielding the highest relative average deviation of 9.56 %. A technique based on inverse Kirkwood–Buff integrals was used to investigate the preferential solvation of TMCA at 298.15 K. The preferential solvation parameters of TMCA showed positive values in isopropanol/acetone/methanol/ethanol -medium and -rich compositions, indicating that isopropanol/acetone/methanol/ethanol preferentially solvated TMCA. Dissolution of TMCA in these aqueous cosolvent solutions was an endothermic process.

Ursolic Acid and Oleanolic Acid Dissolved in Methanol/Acetone + Water Blends: Thermodynamic Solubility, Intermolecular Interactions, and Solvation Behavior

With the purpose of qualitative characterization of the electrostatic properties of the acidity and basicity of ursolic acid (UA) and oleanolic acid (OA), quantitative analyses of the molecular surface were employed in this contribution. The −OH and −COOH groups on the molecules of OA and UA took precedence over establishing hydrogen bonds with the solvents acetone/methanol/water. In addition, the intermolecular interactions of OA and UA with acetone/methanol/water were investigated using an independent gradient model based on the Hirshfeld partition of molecular density. In solutions of OA/UA dissolved in methanol/acetone/water, attractive interactions, including the hydrogen-bond force and van der Waals (vdW) force, occur. The shake-flask technique was applied to evaluate the equilibrium solubility of UA and OA in acetone + water and methanol + water at 101.2 kPa and elevated temperatures covering from 278.15 to 323.15 K. Solvent–solvent interactions accounted by the solubility parameter of solutions had a significant domination in the variability of solubility magnitudes. The van’t Hoff–Jouyban–Acree, Apelblat, and Jouyban–Acree models revealed a good correlation for the measured solubility, with a relative mean deviation of no more than 7.73%. The Kirkwood–Buff integral approach was utilized to determine the preferred solvation of UA and OA by solvent species. In both the rich- and intermediate-composition regions of methanol/acetone, UA or OA is preferentially solvated with positive preferential solvation parameters by methanol/acetone.

Solubility determination, hansen solubility parameter, solvent effect and preferential solvation of thenalidine in four aqueous binary mixtures

The equilibrium solubility of thenalidine in four solvent mixtures (ethanol + water, n-propanol + water, isopropanol + water, and N,N-dimethylformamide (DMF) + water) was studied using the isothermal saturation method at temperatures ranging from 278.15 to 323.15 K under 101.2 kPa. For the mixed systems, the increase in temperature was positively correlated with an increase in solute dissolution. Besides, the water content in the solvent was also a variable that cannot be ignored in the dissolution results. The solubility data in mixed solvents were correlated and calculated by Jouyban-Acree model (J-A), van’t Hoff-Jouyban-Acree model (V-J-A) and Modified Apelblat-Jouyban-Acree model (A-J-A). The largest values of the relative average deviation (RAD) and the root-mean-square deviation (RMSD) were 4.75 × 10−2 and 0.79 × 10−4, respectively. These values were obtained upon using n-propanol + water and DMF + water, respectively. The Hansen solubility parameter was effective for exploring the dissolution behavior of thenalidine in different solvents considering the interaction between solvent and solute molecules. Furthermore, the solvent effect related to thenalidine dissolution was evaluated through the KAT-LSER model, which indicated that the solute–solvent molecule interactions were critical. Finally, the derivation of the preferential solvation parameters (δx1,3) of thenalidine was achieved by the method of inverse Kirkwood–Buff integrals. For ethanol/n-propanol/isopropanol + water, the thenalidine was preferentially dissolved in ethanol/n-propanol/isopropanol within intervals of 1 > x1 > 0.24, 1 > x1 > 0.19 and 1 > x1 > 0.13, respectively. In contrast, thenalidine dissolved preferentially in water in other intervals. However, for DMF + water, |δx1,3| was less than 1 × 10−2, thus, the preferential solvation theory was not applicable for this system.

Solubility of Biocompounds 2,5-Furandicarboxylic Acid and 5-Formylfuran-2-Carboxylic Acid in Binary Solvent Mixtures of Water and 1,4-Dioxane

The solubility of 2,5-furandicarboxylic acid (FDCA) and its synthetic intermediates (e.g., 5-formylfuran-2-carboxylic acid, FFCA) provides fundamental information for the preparation and purification of the value-added biocompound FDCA. We measured the solubility of FDCA and FFCA in binary water + 1,4-dioxane mixtures with different mixing ratios at 303.15 K–342.15 K. The obtained solubility values were correlated with the Jouyban-Acree-van’t Hoff model, and the preferential solvation theory was used to study the microscopic dissolution mechanism. The solubility of FDCA/FFCA increases with increasing temperature, and pure 1,4-dioxane dissolves more solutes than pure water. FFCA shows higher solubility than FDCA. In the binary solvent mixtures, the phenomenon of co-solvency exists for both FDCA and FFCA, i.e., at a 1,4-dioxane mole fraction of about 0.60, FDCA and FFCA dissolve the most. Acceptable mean percentage deviations (MPD) (5.5% and 6.9%) are obtained for FDCA and FFCA (Jouyban-Acree-van’t Hoff model). The calculated preferential solvation parameters show different dissolution mechanisms at different solvent compositions. When the 1,4-dioxane mole fraction is 0.17~0.62/0.63, FDCA/FFCA are preferentially solvated by 1,4-dioxane. Otherwise, they are preferentially solvated by water. A trend similar to the “co-solvency phenomenon” is observed in the differences in solubility of FFCA and FDCA. This study gives important guidance for the use of binary water and 1,4-dioxane solvents in practical FDCA purification.

Solubility Profile and Intermolecular Force Analysis of Nimesulide (Form I) in Mono- and Mixed Solvents at Several Temperatures

The solubility data of nimesulide (form I) in different mono- and mixed solvents over the temperature range from 273.15 to 318.15 K are determined. In this work, it is further studied to improve the solubility data of nimesulide (form I) and analyze the intermolecular force. The solubility profiles in mono- and mixed solvents are correlated by some thermodynamic models. The results of statistical analysis show that all selected models could provide a good correlation of the dissolution profile for nimesulide in selected solvents at all investigated temperatures. At 318.15 K, the largest solubility in mole fraction is obtained in acetone (7.812 × 10–2), followed by 2-butanone (6.334 × 10–2), cyclohexanone (4.977 × 10–2), ethyl acetate (3.803 × 10–2), tetrahydrofuran (3.651 × 10–2), acetonitrile (2.975 × 10–2), ethanol (2.169 × 10–3), toluene (1.788 × 10–3), isobutanol (1.348 × 10–3), isopropanol (1.201 × 10–3), and propylene glycol (PG, 6.764 × 10–4). However, in mixtures of (ethyl acetate + isopropanol), the solubility data increase with the increase of the mass fraction of ethyl acetate at a given temperature. The effect of solute–solvent interactions on the solid–liquid phase equilibrium of the solute is discussed with the solvent properties. The calculation of preferential solvation parameters shows that solute molecules are preferentially solvated by isopropanol in isopropanol-rich regions and as the mass fraction of ethyl acetate increases, nimesulide is preferentially solvated by ethyl acetate. Studying the dissolution process of nimesulide is of great practical significance for its purification.

Effect of N-Methyl-pyrrolidone (NMP) on the Equilibrium Solubility of Meloxicam in Aqueous Media: Correlation, Dissolution Thermodynamics, and Preferential Solvation.

Meloxicam is an analgesic and anti-inflammatory drug widely prescribed in current therapeutics that exhibits very low solubility in water. Thus, this physicochemical property has been studied in N-methyl-pyrrolidone (NMP)–aqueous mixtures at several temperatures to expand the solubility database about pharmaceutical compounds in aqueous–mixed solvents. The flask-shake method and UV–vis spectrophotometry were used for meloxicam solubility determination as a function of temperature and mixture composition. Several cosolvency models, including the Jouyban–Acree model, were challenged for equilibrium solubility correlation and/or prediction. The van’t Hoff and Gibbs equations were employed here to calculate the apparent standard thermodynamic quantities for the dissolution and mixing processes of this drug in these aqueous mixtures. Inverse Kirkwood–Buff integrals were employed to calculate the preferential solvation parameters of meloxicam by NMP in all mixtures. Meloxicam equilibrium solubility increased with increasing temperature, and maximal solubilities were observed in neat NMP at all temperatures. The mole fraction solubility of meloxicam increased from 1.137 × 10–6 in neat water to 3.639 × 10–3 in neat NMP at 298.15 K. The Jouyban–Acree model correlated the meloxicam solubility in these mixtures very well. Dissolution processes were endothermic and entropy-driven in all cases, except in neat water, where nonenthalpy- nor entropy-driven was observed. Apparent Gibbs energies of dissolution varied from 34.35 kJ·mol–1 in pure water to 7.99 kJ·mol–1 in pure NMP at a mean harmonic temperature of 303.0 K. A nonlinear enthalpy–entropy relationship was observed in the plot of dissolution enthalpy vs dissolution Gibbs energy. Meloxicam is preferentially hydrated in water-rich mixtures but preferentially solvated by NMP in the composition interval of 0.16 < x1 < 1.00.

Solubility, solvent effect, preferential solvation and DFT computations of 5-nitrosalicylic acid in several aqueous blends

The purpose of this contribution was to investigate the solubility, computational techniques, solvent effect, and preferential solvation of 5-nitrosalicylic acid in blended solvents of acetonitrile/N,N-dimethylformamide(DMF)/methanol/n-propanol + water. Visualizing regions of weak contact between 5-nitrosalicylic acid and solvent using an independent gradient model based on Hirshfeld partitioning (IGMH), and providing a quantitative study for the molecule’s electrostatic characteristics using a molecular surface research and Hirshfeld surface analysis were carried out. All equilibrium solubility measurements were performed using a shake-flask technique at temperatures from 278.15 to 323.15 K and pressure of 101.2 kPa. For each blends studied, the lowest solubility was observed at 278.15 K in water and the highest at 323.15 K in pure organic solvent. Using linear solvation energy relationships, the effect of molecular interactions on solubility variation was studied, revealing that the solubility parameter and dipolarity-polarizability played a substantial impact in solubility variation. By correlating the derived equilibrium solubilities with the Jouyban-Acree, modified Apelblat-Jouyban-Acree, and van't Hoff–Jouyban–Acree models, a maximum relative average deviation of 4.01 percent was obtained. Quantitative investigation of the solvation behavior of 5-nitrosalicylic acid by solvent species was conducted using the method of inverse Kirkwood–Buff integrals. Positive values of the preferential solvation parameter in acetonitrile/DMF/methanol/n-propanol-middle and -rich blended systems indicated that acetonitrile/DMF/methanol/n-propanol solvated 5-nitrosalicylic acid preferentially. In the above composition ranges, it is hypothesized that 5-nitrosalicylic acid interacts with nearby methanol/DMF/n-propanol molecules as a Lewis acid, whereas solvation by acetonitrile is due to the polarization effect.

Nitazoxanide in aqueous co-solvent solutions of isopropanol/DMF/NMP: Solubility, solvation thermodynamics and intermolecular interactions

At the microscopic level, quantitative surface analysis was utilized to highlight the electrostatic features of acidity and basicity, respectively. The groups of –NO2 and > NH are the principal sites of electrophilic and nucleophilic attack, respectively, on the nitazoxanide (NTZ) molecule. The weak interaction regions between NTZ and solvent were visually examined through the IGMH method. The solubility of NTZ in three co-solvent blends, namely isopropanol + water, DMF + water, and NMP + water, was determined over a temperature range of 278.15 to 323.15 K. The isothermal saturation method was used to obtain the results, which were carried out under a pressure of 101.2 kPa. No evidence of crystal transition or solvate production was observed in the experiments conducted. Under the same investigational conditions, such as the same temperature and composition of isopropanol (DMF or NMP), the NTZ solubility in mole fraction was significantly greater in aprotic DMF/NMP + water blends than in protic isopropanol + water blends. Five models were used to relate solubility data: the Jouyban–Acree model, the extended Hildebrand solubility model, the modified Jouyban–Acree-van't Hoff model, the NRTL model and the UNIQUAC model. Under the conditions of 298.15 K, an investigation into the preferential solvation of NTZ was carried out using a technique based on inverse Kirkwood–Buff integrals. With isopropanol/DMF/NMP-medium and -rich composition areas, the preferential solvation parameters of NTZ showed positive values, indicating that the co-solvents were preferentially solvating the drug.

Increasing the Equilibrium Solubility of Meloxicam in Aqueous Media by Using Dimethyl Sulfoxide as a Cosolvent: Correlation, Dissolution Thermodynamics and Preferential Solvation

Meloxicam is widely prescribed as an analgesic and anti-inflammatory drug in human therapeutics. Owing the very low aqueous solubility of meloxicam, this property has been studied in dimethyl sulfoxide (DMSO)-aqueous solvent systems at several temperatures from 273.15 to 313.15 K to expand the solubility database about analgesic drugs in mixed solvents. The flask shake method followed by ultraviolet-visible (UV-vis) spectrophotometry analysis were used for meloxicam solubility determinations. A number of cosolvency models, including the Jouyban–Acree model, were challenged for solubility correlation/prediction of this drug in these mixtures. The van’t Hoff and Gibbs equations were employed to calculate the apparent standard thermodynamic quantities relative to dissolution and mixing processes. The inverse Kirkwood–Buff integral method was employed for calculating the preferential solvation parameters of meloxicam by DMSO in the mixtures. Meloxicam solubility increases with increasing temperature and maximum solubilities are observed in neat DMSO at all temperatures studied. Dissolution processes were endothermic in all cases and entropy-driven in the composition interval of 0.40 ≤ x1 ≤ 1.00. A nonlinear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy for drug transfer processes. Meloxicam is preferentially solvated by water in water-rich mixtures but preferentially solvated by DMSO in the composition interval of 0.21 &lt; x1 &lt; 1.00.

Spectroscopic investigation of preferential solvation of N-confused tetraphenylporphyrinin binary mixtures of dichloromethane with organic cosolvents

Spectroscopic behaviour of porphyrin is known to be sensitive to the choice of the solvent and has been used to probe solvation phenomena. The UV–visible spectra of N-confused tetraphenylporphyrin are observed in a series of binary solvent mixtures – (dichloromethane + diethyl ether), (dichloromethane + chlorobenzene) and (dichloromethane + ethyl acetate). The resulting ET scale for NCTPP solvation indicates nonlinear behaviour and preferential solvation by a solvent–solvent complex in all the three solvents – with the dichloromethane + ethyl acetate system showing the largest deviation from ideality. The data is fitted to the model based on solvent exchange equilibria for determining the preferential solvation parameters which are specific to the probe as well as the identity of solvents in the binary mixture. Further analysis using polarity parameters from literature indicate that the solvation of NCTPP in the (dichloromethane + ethyl acetate) mixture is dependent on the hydrogen bond accepting capacity and polarizability of the medium. Excess spectra derived from ATR-FTIR measurement of dichloromethane + ethyl acetate solutions lead to important inferences about the structure and role of solvent–solvent interactions responsible for the preferential solvation.

Preferential solvation of 5,7-dihydroxyflavone (chrysin) in aqueous co-solvent mixtures of methanol and ethanol

ABSTRACT The inverse Kirkwood-Buff integrals were used to calculate the preferential solvation parameters of the natural polyphenolic compound chrysin in binary mixtures of ethanol (1) + water (2) and methanol (1) + water (2) as a function of their thermodynamic properties. At temperatures between 298.15 K and 318.15 K, chrysin is extremely sensitive to specific solvation effects; therefore, the negative values of were found in the water-rich range of 0 < x1 < 0.30 for methanol (1) + water (2) and 0 < x1 < 0.25 for ethanol (1) + water (2) which suggested that water (2) preferentially dissolves chrysin (3). In co-solvent-rich regions, the values of were positive, and the co-solvents preferentially dissolve chrysin (3). The solvation of drugs in water-rich mixtures is likely to be facilitated by hydrophobic hydration around aromatic rings or groups.