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.

Solvatochromism, Preferential Solvation and Multiparametric Approach to the Spectral Shift of Methyl Orange in Aqueous Cosolvent Mixtures.

In this study, the solvatochromic behavior of Methyl orange was studied visible spectrophotometrically in seven aqueous binary systems from water with methanol, ethanol, propanol, DMF, DMSO, acetone and dioxane solvents. The spectral data was interpreted in terms of solute-solvent and solvent-solvent interactions. The deviation from linearity in the plots of νmax versus x2 due to preferential solvation of the Methyl orange by one component of the mixed solvent and due to solvent microheterogeneity. The preferential solvation parameters local mole fraction X2L, solvation index δs2 and exchange constant K12 were evaluated. The preference of solute to be solvated by one of the solvating species relative to others was explained. All values of K12 were less than unity that indicates the preferential solvation of Methyl orange by water, except in case the water-propanol mixture where K12 was higher than unity. The preferential solvation index δs2 values were calculated and interpreted for each binary mixture. The magnitude of preferential solvation index was highest in water-DMSO mixtures than in the all other solvent mixtures. The energy of electronic transition in maximum absorption (ET) was calculated in each binary mixture. The extent and importance of each solute-solvent interactions to ET were analyzed by the linear solvation energy relationships using the Kamlet-Taft strategy.

Effect of the Temperature on the Process of Preferential Solvation of 1,4-Dioxane, 12-Crown-4, 15-Crown-5 and 18-Crown-6 Ethers in the Mixture of N-Methylformamide with Water: Composition of the Solvation Shell of the Cyclic Ethers.

The aim of the work was to analyze the preferential solvation process, and determine the composition of the solvation shell of cyclic ethers using the calorimetric method. The heat of solution of 1,4-dioxane, 12-crown-4, 15-crown-5 and 18-crown-6 ethers in the mixture of N-methylformamide with water was measured at four temperatures, 293.15 K, 298.15 K, 303.15 K, and 308.15 K, and the standard partial molar heat capacity of cyclic ethers has been discussed. 18-crown-6 (18C6) molecules can form complexes with NMF molecules through the hydrogen bonds between -CH3 group of NMF and the oxygen atoms of 18C6. Using the model of preferential solvation, the cyclic ethers were observed to be preferentially solvated by NMF molecules. It has been proved that the molar fraction of NMF in the solvation shell of cyclic ethers is higher than that in the mixed solvent. The exothermic, enthalpic effect of preferential solvation of cyclic ethers increases with increasing ring size and temperature. The increase in the negative effect of the structural properties of the mixed solvent with increase in the ring size in the process of preferential solvation of the cyclic ethers indicates an increasing disturbance of the mixed solvent structure, which is reflected in the influence of the energetic properties of the mixed solvent.

Composition of the Solvation Shell of the Selected Cyclic Ethers (1,4-Dioxane, 12-Crown-4, 15-Crown-5 and 18-Crown-6) in a Mixture of Formamide with Water at Four Temperatures.

The solution enthalpy of 15-crown-5 and 18-crown-6 ethers in the mixture of formamide (F) and water (W) was measured at four temperatures: 293.15 K, 298.15 K, 303.15 K, 308.15 K. The standard molar enthalpy of solution, ΔsolHo, depends on the size of cyclic ethers molecules and the temperature. With increasing temperature, the values of ΔsolHo become less negative. The values of the standard partial molar heat capacity Cp,2o of cyclic ethers at 298.15 K have been calculated. The Cp,2o=f(xW) curve shape indicates the hydrophobic hydration process of cyclic ethers in the range of a high-water content in the mixture with formamide. The enthalpic effect of preferential solvation of cyclic ethers was calculated and the effect of temperature on the preferential solvation process was discussed. The process of complex formation between 18C6 molecules and formamide molecules is observed. The cyclic ethers molecules are preferentially solvated by formamide molecules. The mole fraction of formamide in the solvation sphere of cyclic ethers has been calculated.

Does Urea Preferentially Interact with Amide Moieties or Nonpolar Sidechains? A Question Answered Through a Judicious Selection of Model Systems.

The transfer model suggests that urea unfolds proteins mainly by increasing the solubility of the amide backbone, probably through urea-induced increase in hydrogen bonding. Other studies suggest that urea addition increases the magnitude of solvent-solute van der Waals interactions, which increases the solubility of nonpolar sidechains. More recent analyses hypothesize that urea has a similar effect in increasing the solubility of backbone and sidechain groups. In this work, we compare the effects of urea addition on the solvation of amides and alkyl groups. At first, we study the effects of urea addition upon solvent hydrogen bonding acidity and basicity through the perturbation in the fluorescence spectrum of probes 1-AN and 1-DMAN. Our results demonstrate that the solvent's hydrogen bonding properties are minimally affected by urea addition. Subsequently, we show that urea addition does not perturb the intra-molecular hydrogen bonding in salicylic acid significantly. Finally, we investigate how urea preferentially interacts with amide and alkyl groups moieties in water by comparing the effects of urea addition upon the solubility of acetaminophen and 4-tertbutylphenol. We show that urea affects amide and t-butyl solubility (lowers the transfer free energy of both amide (backbone) and alkyl (sidechain) groups) in a similar fashion. In other words, preferential interaction of urea with both moieties contributes to protein denaturation.

Absolute molar mass determination in mixed solvents. 2. SEC/MALS/DRI in a mix of two "nearly-isovirial" solvents.

The accurate determination of polymer molar mass (M) averages and distributions via size-based separation methods employing mixed solvents remains one of the great macromolecular characterization challenges. This is due to the possibility for preferential solvation, whereby the region in the immediate vicinity of the polymer in solution becomes enriched in one of the solvents as compared to this solvent's fractional amount in the mix. In such cases, the chromatographic baselines of differential detectors such as light scattering photometers and differential refractometers no longer provide a quantitative reflection of the solvents' contribution to the heights of individual peak slices, thereby introducing error into molar mass calculations. The problem is addressed here through the use of a "nearly-isovirial" solvent pair. The second virial coefficient (A2) of both solvents being nearly equal for the polymers analyzed means that preferential solvation is obviated. The accuracy of this approach is shown via analysis by size-exclusion chromatography with on-line multi-angle static light scattering and differential refractometry detection (SEC/MALS/DRI), for a trio of narrow-dispersity polystyrene (PS) standards covering a nearly 40-fold range in M. In a mix of two nearly isovirial solvents, namely tetrahydrofuran (THF) and toluene, calculated molar mass averages and distributions are shown to be essentially identical across the range of solvent ratios. Polymer size is likewise shown to be constant with solvent ratio in this scenario. This is contrasted with the same polymers dissolved in a mix of the non-isovirial, non-isorefractive solvents THF and dimethylformamide (DMF). Results from this latter set of experiments show the large error in calculated M that results from preferential solvation, which can be as high as ≈ 1 × 105 g mol-1 for an 8 × 105 g mol-1 narrow-dispersity polystyrene. It is determined that, for a 25:75 THF:DMF mix, the solvent ratio in the immediate vicinity of the polymers examined "flips" to ≈75:25 THF:DMF due to preferential solvation.

Dissolution thermodynamics and preferential solvation of genistein in some (ethanol + water) mixtures at different temperatures.

The solubility of genistein was measured in the binary system of ethanol and water at temperatures ranging from 288.2 to 328.2 K. The obtained data were correlated with the modified Apelblat model, Yalkowsky model, λh model, CNIBS/R-K model, Jouyban-Acree-van't Hoff model, and modified Wilson model and their prediction accuracy was evaluated by calculating the mean relative deviation. The thermodynamic functions, Gibbs energy, enthalpy, and entropy of solution were determined using van't Hoff equation. Moreover, the preferential solvation was analyzed by using the solubility data at 298.2 K. The solubility of genistein in the system increased with an increase in temperature and mole fraction of ethanol in the solvent mixtures. The values for solubility of genistein are ranging from 0.47 obtained in neat water at T = 288.2 K to 5.02 obtained in absolute ethanol at T = 328.2 K. The values of ΔsolnG,0 ΔsolnH0 and ΔsolnH0 for the dissolution of genistein in mixtures are positive, whereas the values of ΔsolnH0 in neat water and absolute ethanol are negative. The thermodynamic properties of dissolution suggest that the dissolution process is non-spontaneous and endergonic. The modified Apelblat model can provide more accurate predictive solubility of genistein in the water and ethanol mixtures, whereas Yalkowsky model calculates solubility of genistein with large deviations. Genistein is preferentially solvated by water in water-rich mixtures (0 < x2 < 0.24) but preferential solvation by ethanol in the region of 0.24 < x2 < 1. Overall, this work could be applied for designing and optimizing the extraction, purification, and crystallization process of genistein.

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.

3-aminoquinoline: a turn-on fluorescent probe for preferential solvation in binary solvent mixtures.

3-Aminoquinoline (3AQ) has been used as a fluorescent probe for preferential solvation in hexane-ethanol solvent mixtures. Results of the present experiment have been put into context by comparison with prior observations with 5-aminoquinoline (5AQ) as the probe. 3AQ exhibits a relatively small change of dipole moment (Δµ= 2.2 D) upon photoexcitation, compared to 5AQ (Δµ= 6.1D), which might appear to be a hindrance in the way of its use as a solvation probe. Indeed, the values of parameters like spectral shifts are smaller for the present experiment with 3AQ. At the smallest concentration of alcohol used, its local mole fraction around the probe is significantly lower than in the previous experiments with 5AQ. However, these apparent disadvantages are outweighed by the significant increase in fluorescence intensity and lifetime observed with increasing concentration of ethanol in the solvent mixture, as opposed to the drastic fluorescence quenching that occurs for 5AQ. This is a marked advantage in the use of 3AQ in studies like the present one. The local mole fraction of ethanol and preferential solvation index experienced by 3AQ are in line with those reported for 5AQ. The disadvantage of the smaller magnitude of Δµpersists in the time resolved fluorescence experiments, for solvent mixtures with very low ethanol content. Negligible wavelength dependence of fluorescence transients of 3AQ is observed forxp= 0.002,. However, this effect is outweighed at higher alcohol concentrations, for which nanosecond dynamics of preferential solvation is observed.

Poly(vinyl pyridine) and Its Quaternized Derivatives: Understanding Their Solvation and Solid State Properties.

A series of N-methyl quaternized derivatives of poly(4-vinylpyridine) (PVP) were synthesized in high yields with different degrees of quaternization, obtained by varying the methyl iodide molar ratio and affording products with unexplored optical and solvation properties. The impact of quaternization on the physicochemical properties of the copolymers, and notably the solvation properties, was further studied. The structure of the synthesized polymers and the quaternization degrees were determined by infrared and nuclear magnetic spectroscopies, while their thermal characteristics were studied by differential scanning calorimetry and their thermal stability and degradation by thermogravimetric analysis (TG-DTA). Attention was given to their optical properties, where UV-Vis and diffuse reflectance spectroscopy (DRS) measurements were carried out. The optical band gap of the polymers was calculated and correlated with the degree of quaternization. The study was further orientated towards the solvation properties of the polymers in binary solvent mixtures that strongly depend on the degree of quaternization, enabling a better understanding of the key polymer (solute)-solvent interactions. The assessment of the underlying solvation phenomena was performed in a system of different ratios of DMSO/H2O and the solvatochromic indicator used was Reichardt's dye. Solvent polarity parameters have a significant effect on the visible spectra of the nitrogen quaternization of PVP studied in this work and a detailed path towards this assessment is presented.

Solubility of Sulfamethazine in the Binary Mixture of Acetonitrile + Methanol from 278.15 to 318.15 K: Measurement, Dissolution Thermodynamics, Preferential Solvation, and Correlation.

Solubility of sulfamethazine (SMT) in acetonitrile (MeCN) + methanol (MeOH) cosolvents was determined at nine temperatures between 278.15 and 318.15 K. From the solubility data expressed in molar fraction, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van 't Hoff equations; on the other hand, the solubility data were modeled according to the Wilson models and NRTL. The solubility of SMT is thermo-dependent and is influenced by the solubility parameter of the cosolvent mixtures. In this case, the maximum solubility was achieved in the cosolvent mixture w0.40 at 318.15 K and the minimum in pure MeOH at 278.15 K. According to the thermodynamic functions, the SMT solution process is endothermic in addition to being favored by the entropic factor, and as for the preferential solvation parameter, SMT tends to be preferentially solvated by MeOH in all cosolvent systems; however, δx3,1<0.01, so the results are not conclusive. Finally, according to mean relative deviations (MRD%), the two models could be very useful tools for calculating the solubility of SMT in cosolvent mixtures and temperatures different from those reported in this research.

Anion solvation enhanced by positive supercharging mutations preserves thermal stability of an antibody in a wide pH range.

Proteins function through interactions with other molecules. In protein engineering, scientists often engineer proteins by mutating their amino acid sequences on the protein surface to improve various physicochemical properties. "Supercharging" is a method to design proteins by mutating surface residues with charged amino acids. Previous studies demonstrated that supercharging mutations conferred better thermal resistance, solubility, and cell penetration to proteins. Likewise, antibodies recognize antigens through the antigen-binding site on the surface. The genetic and structural diversity of antibodies leads to high specificity and affinity toward antigens, enabling antibodies to be versatile tools in various applications. When assessing therapeutic antibodies, surface charge is an important factor to consider because the isoelectric point plays a role in protein clearance inside the body. In this study, we explored how supercharging mutations affect physicochemical properties of antibodies. Starting from a crystal structure of an antibody with the net charge of -4, we computationally designed a supercharged variant possessing the net charge of +10. The positive-supercharged antibody exhibited marginal improvement in thermal stability, but the secondary structure and the binding affinity to the antigen (net charge of +8) were preserved. We also used physicochemical measurements and molecular dynamics simulations to analyze the effects of supercharging mutations in sodium phosphate buffer with different pH and ion concentrations, which revealed preferential solvation of phosphate ions to the supercharged surface relative to the wild-type surface. These results suggest that supercharging would be a useful approach to preserving thermal stability of antibodies in a wide range of pH, which may enable further diversification of antibody repertoires beyond natural evolution.

Thermodynamic analysis and preferential solvation of gatifloxacin in DMF + methanol cosolvent mixtures / Análisis termodinâmico y solvatación preferencial de gatifloxacina en mezclas cosolventes DMF + metanol

SUMMARY This paper presents the thermodynamic analysis of solubility of gatifloxacin in the N,N-Dimethylformamide (DMF) + methanol (MeOH) cosolvent system at 10 temperatures. From the solubility data, the thermodynamic functions of solution, mixing, and transfers are calculated and analyzed using the Perlovich graphical method. On the other hand, an enthalpy-entropy compensation analysis is performed and the preferential solvation parameters are calculated using the inverse Kirkwood-Buff integral (IKBI) method. The result of the performed calculations indicates that the gatifloxacin solution process is endothermic with entropic favor, where the addition of DMF has a positive cosolvent effect in all cases. Regarding preferential solvation, the results are not entirely conclusive, since in all cases the values of the preferential solvation parameter are less than 0.01, so that, negligible preferential solvation takes place.

RESUMEN Este artículo presenta el análisis termodinâmico de la solubilidad de gatifloxacina en el sistema cosolvente de A,A-Dimetilformamida (DMF) + metanol (MeOH) a 10 temperaturas. A partir de los datos de solubilidad se calculan las funciones termodinámicas de solución, mezcla y transferencia. Para el análisis además se utiliza el método gráfico Perlovich. Por otro lado, se realiza un análisis de compensación entalpía-entropía y se calculan los parámetros de solvatación preferencial utilizando el método de las integrales inversas de Kirkwood-BufF (IIKB). Los resultados del análisis termodinámico indican que el proceso de solución de gatifloxacina es endotérmica con favorecimiento entrópico, donde la adición de DMF tiene un efecto cosolvente positivo en todos los casos. En cuanto a la solvatación preferencial, los resultados no son del todo concluyentes, debido a que en todos los casos los valores del parámetro de solvatación preferencial son menores a 0,01 indicando una solvatación insignificante.

Approaches to Understanding the Solution-State Organization of Spray-Dried Dispersion Feed Solutions and Its Translation to the Solid State.

It is well established that polymers adopt a range of conformations and solution-state organization in response to varying solution environments, although very little work has been done to understand how these effects might impact the physical stability and bioavailability of spray-dried amorphous dispersions (SDDs). Potentially relevant solution-state polymer-solvent/cosolute interactions include preferential solvation, hydrodynamic size (i.e., polymer swelling or collapse), and solvent quality effects (i.e., attractive or repulsive self-interactions). Of particular interest is the investigation of preferential solvation, defined as the relative attraction or rejection of a cosolvent and/or cosolute from the local environment of a solvated macromolecule, which often occurs in multicomponent macromolecular solutions. As spray drying and other solvent-based dispersion processing necessitates the use of complex media consisting of at least three or more components (drug, polymer, solvent(s), and other possible excipients), the prevalence of this phenomenon is likely. This work characterizes largely unexplored solution-state properties in model spray-dried dispersion feed solutions using light scattering and viscometric techniques to add greater context and guidance in studying these information-rich materials. These systems are found to exhibit complex non-intuitive behavior, which serves to highlight the potential utility of preferential solvation in spray-dried dispersion processing and stability. It is hypothesized that solution-state organization of the liquid feed can be engineered and translated to the solid-state for the optimization of SDD properties.

Conformational dynamics of [Formula: see text]-conotoxin PnIB in complex solvent systems.

Cone snails are slow-moving animals that secure survival by injecting to their prey a concoction of highly potent and stable neurotoxic peptides called conotoxins. These small toxins (~ 10-30 AA) interact with ion channels and their diverse structures account for various variables such as the environment and the prey of preference. This study probed the conformational space of α-conotoxin PnIB from Conus pennaceus by performing all-atom molecular dynamics simulations on the conotoxin in complex solvent systems of water and octanol. Secondary structure analyses showed a uniform conformation for the pure (C100Oc, C100W) and minute (C95Oc, C5Oc) systems. In C50Oc, however, structural changes were observed. The original helices were converted to turns and were shown to happen simultaneously with the elongation of the helix and shortening of end-to-end distance. The transitions complement the orientation of the peptide at the interface. The shift to the broken helix conformation is marked by the rearrangement of solvent molecules to a framework that favors the accumulation of water molecules at residues 6-11 of the H2 region. This promotes specific protein-solvent interactions that facilitate secondary structure transitions. As PnIB has shown favorable binding toward neuronal nicotinic acetylcholine receptors, this study may provide insights on this conotoxin's therapeutic potential. Description: Structural changes in PnIB are accompanied by a simultaneous change in solvent density.

Preferential Ion Microsolvation in Mixed-Modifier Environments Observed Using Differential Mobility Spectrometry.

The preferential solvation behavior for eight different derivatives of protonated quinoline was measured in a tandem differential mobility spectrometer mass spectrometer (DMS-MS). Ion-solvent cluster formation was induced in the DMS by the addition of chemical modifiers (i.e., solvent vapors) to the N2 buffer gas. To determine the effect of more than one modifier in the DMS environment, we performed DMS experiments with varying mixtures of water, acetonitrile, and isopropyl alcohol solvent vapors. The results show that doping the buffer gas with a binary mixture of modifiers leads to the ions binding preferentially to one modifier over another. We used density functional theory to calculate the ion-solvent binding energies, and in all cases, calculations show that the quinolinium ions bind most strongly with acetonitrile, then isopropyl alcohol, and most weakly with water. Computational results support the hypothesis that the quinolinium ions bind exclusively to whichever solvent they have the strongest interaction with, regardless of the presence of other modifier gases.

Effect of preferential solvation and bimolecular quenching reactions on 3OCE in acetonitrile and 1,4-dioxane binary mixtures by optical absorption and fluorescence studies.

Fluorescence quenching and preferential solvation of a coumarin derivative, namely 3-[2-oxo-2-(2-oxo-2H-chromen-3-yl)-ethylidene]-1,3-dihydro-indol-2-one (3OCE), with aniline used as a quencher in solvent mixtures of acetonitrile (AN) and 1,4-dioxane (DX) was carried out at steady state. Suppan's theory of dielectric enrichment was used to understand the nonideality and dielectric enrichment in AN-DX solvent mixtures. The effect of viscosity and dielectric constant variation at room temperature were analyzed. Quenching was characterized using Stern-Volmer plots with an upward curvature. It was found that 3OCE underwent combined static and dynamic quenching that was evident from the quenching rate parameters.

Activation of Electrophile/Nucleophile Pair by a Nucleophilic and Electrophilic Solvation in a SNAr Reaction.

Nucleophilic aromatic substitution reactions of 4-chloroquinazoline toward aniline and hydrazine were used as a model system to experimentally show that a substrate bearing heteroatoms on the aromatic ring as substituent is able to establish intramolecular hydrogen bond which may be activated by the reaction media and/or the nature of the nucleophile.

Preferential solvation of tricin in {ethanol (1) + water (2)} mixtures at several temperatures / Solvatación preferencial de tricin en mezclas etanol + agua a varias temperaturas

SUMMARY The preferential solvation parameters of tricin in {ethanol (1) + water (2)} binary mixtures were obtained from their thermodynamic properties by means of the inverse Kirkwood-Buff integrals method. Tricin is very sensitive to specific solvation effects, so the preferential solvation parameter by ethanol (1), δx 1,3 is negative in the water-rich mixtures but positive in all the other compositions at temperatures from 293.15, to 313.15 K. It is conjecturable that in water-rich mixtures the hydrophobic hydration around the aromatic and methyl groups of the drug plays a relevant role in the solvation. The higher drug solvation by ethanol in mixtures of similar solvent proportions and in ethanol-rich mixtures could be due mainly to polarity effects. In these mixtures, the drug would be acting as Lewis acid with the ethanol molecules because this co-solvent is more basic than water.

RESUMEN Los parámetros de solvatación preferencial del tricina en mezclas {etanol (1) + agua (2)} se obtuvieron a partir de las propiedades termodinámicas de solución, mediante el método de las integrales inversas de Kirkwood-Buff. La tricina es muy sensible a los efectos de solvatación específicos, por lo que el parámetro de solvatación preferencial, δx 1,3 es negativo en las mezclas ricas en agua, pero positivo en todas las otras composiciones a temperaturas desde 293,15 hasta 313,15 K. Se puede establecer que en mezclas ricas en agua la hidratación hidrofóbica alrededor de los grupos aromáticos y metilo del fármaco tiene un papel relevante en la solvatación. La mayor solvatación del fármaco por etanol se presenta en mezclas de proporción intermedia y en mezclas ricas en etanol, esto podría deberse principalmente a los efectos de la polaridad. En estas mezclas, el fármaco actuaría como ácido de Lewis con las moléculas de etanol, puesto que este codisolvente es más básico que el agua.

Preferential solvation bromophenol blue in water-alcohol binary mixture.

In this study, the perichromic behavior of bromophenol blue (BPB) in various binary solvent mixtures was investigated. The binary mixtures considered were comprised of water and methanol (MeOH), ethanol (EtOH), n-propanol (n-PrOH), isopropanol (iso-PrOH) or t-butanol (t-BuOH). The investigation of a preferential solvation model that considers the addition of small quantities of alcohol to water in the presence of bromophenol blue (BPB) is described in this paper. The data obtained were employed to study the preferential solvation (PS) of the probe. It was observed that with increases in the molar fraction of water the spontaneity of the system decreases. This can be explained by the high solubility of BPB in ethanol, with ∆G > 0 at higher wavelengths (region rich in water with violet solution) and ∆G < 0 at lower wavelengths (region rich in alcohol with yellow solution). The pK of the binary mixture changed in all solvents and for all ratios, and the higher the water ratio is the lower the pKIn will be. In binary mixture, an increase in the hydrogen bond acceptor (HBA) nature of the solvents tested resulted in a bathochromic effect on the absorption band of BPB (Δλ = 12 nm). All of the data obtained showed a good nonlinear fit with the mathematical model (SD ≤ 6.6 × 10-3), suggesting that BPB has other potential applications besides its use as a pH indicator.