Water Cosolvent Mixtures Research Articles

Correlation of the solubility of isoniazid in some aqueous cosolvent mixtures using different mathematical models

AbstractSolubility is one of the most important physicochemical properties, because it is related to some industrial processes such as: formulation, preformulation, purification and quantification. The experimental determination of solubility requires rigorous processes that involve a significant amount of resources. In this context, mathematical models allow estimating solubility under conditions different from the experimental ones from a limited number of data. The objective of this research was to evaluate the pertinence of 10 mathematical models (Extended Hildebrand, van’t Hoff, Two-parameter Weibull, Buchowski–Ksiazczak $$\lambda h$$ λ h , van’t Hoff-Yaws, Apelblat, Wilson, NRTL, Modified Wilson and van’t Hoff-Modified Wilson) in the calculation of the solubility of isoniazid in PEG 200 (1) + Water (2) cosolvent mixtures, the parameters of each model were calculated using Python, Pandas and the NumPy and SciPy library. Once each model was evaluated, two models were defined as the best alternatives based on their predictive power and mathematical simplicity. Thus, the van’t Hoff and Modified Wilson models were combined to obtain an equation that allows the calculation of solubility as a function of temperature and cosolvent composition, obtaining MRD% less than 3.0. In conclusion, mathematical models represent a good prediction tool being a potential alternative in relation to the optimization of some industrial processes related to solubility.

PERFORMANCE OF THE JOUYBAN-ACREEAND YALKOWSKY-ROSEMAN MODELSFOR ESTIMATING THE SOLUBILITY OFINDOMETHACIN IN ETHANOL + WATERMIXTURES

Indomethacin (IMC) is an anti-inflammatory drug whose physiochemical properties in aqueous solutions have not been studied thoroughly. For this reason, in this work the validity of the Jouyban-Acree and Yalkowsky-Roseman models is evaluated to predict the solubility of this compound in ethanol + water cosolvent mixtures. The solubility estimation is studied as a function of temperature and cosolvent composition. Both models require only the experimental solubility values in the pure solvents at all the temperatures evaluated. The solubility calculated values by using both models deviate notoriously from experimental values in several cases.

THERMODYNAMIC MAGNITUDES OF MIXING AND SOLVATION OF ACETAMINOPHEN IN ETHANOL + WATER COSOLVENT MIXTURES.

Based on van't Hoff and Gibbs equations the thermodynamic functions free energy, enthalpy, and entropy of solution, mixing and solvation of acetaminophen in ethanol + water cosolvent mixtures, were evaluated from solubility data determined at several temperatures. The solubility was greater at 90% m/m of ethanol at all temperatures studied. This result shows clearly the cosolvent effect present in this system. The solvation of this drug in the mixtures increases as the ethanol proportion is also increased. By means of enthalpy-entropy compensation analysis, a more complex behavior for solution was found with respect to that exposed previously in literature. From 0% up to 10% m/m of ethanol and from 90% up to 100% of ethanol, entropy driving was found, while from 20% up to 60% of ethanol, enthalpy driving was found. These facts would be explained in terms of a losing of water-structure in addition to a diminishing in the energy required for cavity formation in the solvent for mixtures from 20% up to 60% of ethanol. Nevertheless in the ethanol-rich mixtures the intermolecular mechanisms involved in the solution process should be more complex including other physicochemical considerations.

Thermodynamic Assessment of Triclocarban Dissolution Process in N-Methyl-2-pyrrolidone + Water Cosolvent Mixtures.

Solubility is one of the most important physicochemical properties due to its involvement in physiological (bioavailability), industrial (design) and environmental (biotoxicity) processes, and in this regard, cosolvency is one of the best strategies to increase the solubility of poorly soluble drugs in aqueous systems. Thus, the aim of this research is to thermodynamically evaluate the dissolution process of triclocarban (TCC) in cosolvent mixtures of {N-methyl-2-pyrrolidone (NMP) + water (W)} at seven temperatures (288.15, 293.15, 298.15, 303.15, 308.15, 313.15 and 318.15 K). Solubility is determined by UV/vis spectrophotometry using the flask-shaking method. The dissolution process of the TCC is endothermic and strongly dependent on the cosolvent composition, achieving the minimum solubility in pure water and the maximum solubility in NMP. The activity coefficient decreases from pure water to NMP, reaching values less than one, demonstrating the excellent positive cosolvent effect of NMP, which is corroborated by the negative values of the Gibbs energy of transfer. In general terms, the dissolution process is endothermic, and the increase in TCC solubility may be due to the affinity of TCC with NMP, in addition to the water de-structuring capacity of NMP generating a higher number of free water molecules.

Thermodynamic Analysis of the Solubility of Propylparaben in Acetonitrile–Water Cosolvent Mixtures

Parabens are substances used in the food, pharmaceutical and cosmetic industries. Recent studies have indicated that these substances have toxic potential, cause endocrine disruption and can easily bioaccumulate; therefore, their physicochemical properties are of industrial, biological and environmental interest. Due to their potential use in the development of more efficient and cleaner processes, the design of environmental recovery strategies and more reasonable designs for solubility in cosolvent mixtures, studies of thermodynamic analysis and mathematical modeling are of great interest. This research studies the solubility of propylparaben in acetonitrile + water cosolvent mixtures at nine temperatures by UV/Vis spectrophotometry, analyzing the solid phase by differential scanning calorimetry to evaluate possible polymorphic changes. The solubility of propylparaben is an endothermic process, where phase separation occurs at intermediate mixtures, reaching its minimum solubility in pure water at 278.15 K and the maximum solubility in pure acetonitrile at 315.15 K. The experimental data are well-correlated with the va not Hoff, Apelblat and Buchowski–Ksiazaczak models. The results revealed that possible microheterogeneity of the MeCN + W mixture can generate phase separation in intermediate mixtures, possibly due to the formation of solvates or hydrates.

Chiral and Morphological Anisotropy of Supramolecular Polymers Shaped by a Singularity in Solvent Composition.

Understanding the role of solvent in translating molecular anisotropy to supramolecular polymers is in the early stages. A solvent's influence on the strength of different noncovalent interactions can explain anisotropic growth in some cases, but its effect on cooperative processes, particularly in mixed solvents, remains obscure. We report the self-assembly of a series of chiral perylene bisimides in water-cosolvent mixtures, and the results highlight the fascinating influence of solvent-solute interactions on supramolecular anisotropy, both chiral and morphological. The initial assembly is agnostic to solvent composition, resulting in weakly chiral, spherical nanostructures. In an extremely narrow solvent composition range, the nanospheres transform into long, prominently chiral supramolecular polymers. Further, chirality can be fully reversed by changing the good (achiral) cosolvent. We elucidate how solvent modulates specific noncovalent interactions and governs the kinetics and thermodynamics of key processes, such as spontaneous phase segregation, secondary nucleation, and cooperative growth. In the context of supramolecular polymerization, our results encourage one to steer the focus away from the physical attributes of a solvent (polarity, phase diagram, etc.) and toward the complexities of solvent-solute interactions.

Re-Entrant Conformation Transition in Hydrogels.

Hydrogels are attractive materials not only for their tremendous applications but also for theoretical studies as they provide macroscopic monitoring of the conformation change of polymer chains. The pioneering theoretical work of Dusek predicting the discontinuous volume phase transition in gels followed by the experimental observation of Tanaka opened up a new area, called smart hydrogels, in the gel science. Many ionic hydrogels exhibit a discontinuous volume phase transition due to the change of the polymer–solvent interaction parameter χ depending on the external stimuli such as temperature, pH, composition of the solvent, etc. The observation of a discontinuous volume phase transition in nonionic hydrogels or organogels is still a challenging task as it requires a polymer–solvent system with a strong polymer concentration dependent χ parameter. Such an observation may open up the use of organogels as smart and hydrophobic soft materials. The re-entrant phenomenon first observed by Tanaka is another characteristic of stimuli responsive hydrogels in which they are frustrated between the swollen and collapsed states in a given solvent mixture. Thus, the hydrogel first collapses and then reswells if an environmental parameter is continuously increased. The re-entrant phenomenon of hydrogels in water–cosolvent mixtures is due to the competitive hydrogen-bonding and hydrophobic interactions leading to flow-in and flow-out of the cosolvent molecules through the hydrogel moving boundary as the composition of the solvent mixture is varied. The experimental results reviewed here show that a re-entrant conformation transition in hydrogels requires a hydrophobically modified hydrophilic network, and a moderate hydrogen-bonding cosolvent having competitive attractions with water and polymer. The re-entrant phenomenon may widen the applications of the hydrogels in mechanochemical transducers, switches, memories, and sensors.

Experimental Solubility of Ketoconazole, Validation Models, and In vivo Prediction in Human Based on GastroPlus.

The study aimed to identify a suitable cosolvent + water mixture for subcutaneous (sub-Q) delivery of ketoconazole (KETO). The solubility was assessed for several dimethyl acetamide (DMA) + water mixtures at T = 293.2 to 318.2 K and pressure P = 0.1 MPa. The experimental solubility (xe) was validated using the Van 't Hoff and Yalkowsky models and functional thermodynamic parameters (enthalpy ΔsolH°, entropy ΔsolS°, and Gibbs free energy ΔsolG°). The in vitro drug release study was performed at physiological pH, and the data served as the input to GastroPlus, which predicted the in vivo performance of KETO dissolved in a DMA + water cosolvent mixture for sub-Q delivery in human. The maximum solubility (mole fraction) of KETO (9.81 × 10-1) was obtained for neat DMA at 318.2 K whereas the lowest value (1.7 × 10-5) was for pure water at 293.2 K. An apparent thermodynamic analysis based on xe gave positive values for the functional parameters. KETO dissolution requires energy, as evidenced by the high positive values of ΔsolH° and ΔsolG°. Interestingly, ΔsolG° progressively decreased with increasing concentration of DMA in the DMA + water mixture, suggesting that the DMA-based molecular interaction improved the solubilization. Positive values of ΔsolG° and ΔsolS° for each DMA + water cosolvent mixture corroborated the endothermic and entropy-driven dissolution. GastroPlus predicted better absorption of KETO through sub-Q delivery than oral delivery. Hence, the DMA + water mixture may be a promising system for sub-Q delivery of KETO to control topical and systemic fungal infections.

Solution thermodynamics and preferential solvation of sulfamethazine in ethylene glycol + water mixtures

The solubility of sulfamethazine (SMT) in ethylene glycol (EG) + water (W) cosolvent mixtures was determined at nine temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, 313.15 and 318.15 K) by means of the stirring method. From the solubility data, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van´t Hoff equations. On the other hand, the preferential solvation parameters of SMT were determined by means of the method of the inverse integrals of Kirkwood-Buff (IKBI). In general terms, the solubility of SMT is favored by the increase in temperature and the decrease in the polarity of the cosolvent system, thus the maximum solubility is reached in pure EG at 318.15 K and the minimum in pure water at 278.15 K. Gibbs energy is positive in all cases, with a higher contribution from the energy component (enthalpy of solution). Regarding enthalpy-entropic compensation, the process is driven in all cases by the enthalpy of solution. Finally, SMT is preferentially solvated by water in mixtures with higher polarity and by EG in less polar mixtures.

Extraction of lipids from New Zealand fern fronds using near-critical dimethyl ether and dimethyl ether–water–ethanol mixtures

Dimethyl ether (DME), under near-critical conditions, can be used to extract lipids containing valuable fatty acids from wet biomass. In this work, DME, and a mixture of DME with a water–ethanol co-solvent, are used to extract fronds of the fern Cyathea dealbata, and the fatty acid composition of the extract was compared with the fern total lipids obtained by chloroform–methanol extraction. Extraction was carried out by circulating DME through a packed bed of milled undried fern material at pressure of 4.0 MPa, temperature of 58 °C, flow rate of 13.6 kg per kg undried fern material per hour, for 60 min followed by extraction using DME with addition of 5 wt% of a 70% ethanol in water co-solvent mixture until 572 g of co-solvent had been introduced. The total combined yield of DME and DME–ethanol–water extracts was 6.3 wt% of the fronds with the recovery of 88–93% of the major fatty acids (18:3n-3, 16:0, 18:2n-6, 18:1n-9). The remaining residue contained<7% of the fern total lipids. The extracts were slightly enriched in eicosapentaenoic acid (EPA, 95% recovery), while a significant portion of arachidonic acid (ARA, 19%) remained in the residue. The DME and DME–ethanol–water extracts contained 6.9 and 6.1 mg/g of ARA, and 13.4 and 14.2 mg/g of EPA, respectively.

Solubilization, Hansen solubility parameters and apparent thermodynamic parameters of Osimertinib in (propylene glycol + water) cosolvent mixtures

Abstract The solubilization, Hansen solubility parameters (HSPs) and apparent thermodynamic parameters of a novel anticancer medicine osimertinib (OMT) in binary propylene glycol (P) + water (W) cosolvent mixtures were evaluated. The mole fraction solubility (x e) of OMT in various (P + W) cosolvent mixtures including neat P and neat W was determined at T = 298.2–318.2 K and p = 0.1 MPa by applying a saturation shake flask method. HSPs of OMT, neat P, neat W and (P + W) cosolvent compositions free of OMT were also estimated. The x e values of OMT were regressed with Van’t Hoff, modified Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van’t Hoff models with an average errors of &lt;3.0 %. The highest and lowest x e value of OMT was estimated in neat P (2.70 × 10−3 at T = 318.2 K) and neat W (1.81 × 10−5 at T = 298.2 K), respectively. Moreover, HSP of OMT was found to be closed with that of neat P. The solubility of OMT was found to be increased significantly with an increase in temperature and P mass fraction in all (P + W) cosolvent compositions including neat P and neat W. The results of activity coefficients suggested higher molecular interactions in OMT-P combination compared with OMT-W combination. The results of thermodynamic studies indicated an endothermic and entropy-driven dissolution of OMT in all (P + W) cosolvent compositions including neat P and neat W.

Co-solvent exfoliation of layered titanium diboride into few-layer-thick nanosheets

In this work, we present an approach to nanoscale titanium diboride (TiB2), a layered ceramic from the metal diboride family, by investigating its interaction with a co-solvent containing water and isopropanol (IPA). It is gradually being established that layered metal diborides can be exfoliated in liquid phase to yield 2D counterparts. However, these reports have not yet systematically investigated the suitability of a solvent to exfoliate these ionic layered materials. Such a prospect is primarily limited by the fact that the theories available to rationally select exfoliating solvents are applicable only for van der Waals (vdW) layered materials. We show that it is possible to identify an optimal exfoliating medium for TiB2 by using co-solvents. We tested the exfoliation of TiB2 in isopropanol (IPA)-water co-solvent mixtures at different IPA concentrations, and established that a 10% isopropanol-water co-solvent results in optimal exfoliation. The resultant nanosheets are extremely thin (~3–5 nm) and exhibit a mild degree of oxy-functionalization. We observed that the original structural integrity of nanosheets (TiB2 lattice) is maintained to a large extent after exfoliation. We also validated the findings by using Surface Tension Component Matching (STCM) and studied the exfoliation of TiB2 in acetonitrile (ACN). This resulted in a lower degree of exfoliation as expected, but led us to obtain nearly pristine TiB2 nanosheets. The new physical insights presented in this work can serve as a guide to predict the exfoliation of TiB2 in other prospective solvents.

Enhanced Solubility of Modafinil via Solubilization Techniques

<!DOCTYPE html> <html> <head> </head> <body> <p style="text-align: justify;"><strong>Objectives:</strong> The objective of the study was to compare solubilization approaches, namely cosolvency, micelle solubilization, complexation, pH adjustment and hydrotrophy, on BCS class II drug modafinil solubility. <strong>Methods: </strong>Altered solubility study of modafinil was carried out in numerous water-cosolvent mixtures. Similar type of study was performed using different ionic and non-ionic surfactants using phase solubility analysis. Furthermore, solubility behavior with two cyclodextrins namely beta cyclodextrin and maltodextrin were examined. Solubility studies were conducted in buffers of different pH ranging from 1.2 to 8 at different temperatures (25&deg;C and 37&deg;C). The effect of hydrotrophy on the solubility of modafinil was also studied. <strong>Results:</strong> Outcomes showed that ethanol is depicted to enhance solubility by greater height. It is found that ionic surfactants were better solubilizers than non-ionic surfactants. The capacity of solubilization is depicted to enhance with rise in hydrocarbon chain length of surfactant, denoting that hydrocarbon core of micelles as the center of solubilization. Highest solubility and binding constants were achieved with use of beta cyclodextrins followed by maltodextrins. The buffers of pH 2 and pH 3 have shown highest solubility when compared to others. Sodium thiocyanate salt had shown highest solubility of the drug. <strong>Conclusion: </strong>As a consequence, the study provides dataset so as to contrast effects of numerous solubilizers on modafinil solubility and also gives an insight of the mode of solubilization by aforementioned techniques. <p style="text-align: justify;"><strong>Key words: </strong>Modafinil, Complexation, Cosolvency, Hydrotrophy, Solubility, Surfactants. </body> </html>

Fast predictions of liquid-phase acid-catalyzed reaction rates using molecular dynamics simulations and convolutional neural networks.

The rates of liquid-phase, acid-catalyzed reactions relevant to the upgrading of biomass into high-value chemicals are highly sensitive to solvent composition and identifying suitable solvent mixtures is theoretically and experimentally challenging. We show that the complex atomistic configurations of reactant–solvent environments generated by classical molecular dynamics simulations can be exploited by 3D convolutional neural networks to enable accurate predictions of Brønsted acid-catalyzed reaction rates for model biomass compounds. We develop a 3D convolutional neural network, which we call SolventNet, and train it to predict acid-catalyzed reaction rates using experimental reaction data and corresponding molecular dynamics simulation data for seven biomass-derived oxygenates in water–cosolvent mixtures. We show that SolventNet can predict reaction rates for additional reactants and solvent systems an order of magnitude faster than prior simulation methods. This combination of machine learning with molecular dynamics enables the rapid, high-throughput screening of solvent systems and identification of improved biomass conversion conditions.

Thermodynamic analysis and preferential solvation of sulfamethazine in acetonitrile + water cosolvent mixtures

This paper presents the solubility of sulfamethazine (SMT) in the acetonitrile (MeCN) + water (W) cosolvent system at nine temperatures. From the solubility experimental 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 Kirkwood-Buff (IKBI) inverse integral method. The result of the performed calculations indicates that the SMT solution process is endothermic with entropic favor, where the addition of MeCN has a positive cosolvent effect between pure water and the mixture with w1 = 0.90. As for the preferential solvation, the SMT molecule is preferentially surrounded by water in water- and MeCN-rich mixtures, and in intermediate mixtures, the SMT molecule tends to be surrounded by MeCN.

Thermodynamic study of the solubility of ethylparaben in acetonitrile + water cosolvent mixtures at different temperatures

The thermodynamic analysis of the solubility of ethylparaben (1) in acetonitrile (1) + water (2) cosolvent mixtures at 9 temperatures, 10 cosolvent mixtures and the 2 pure solvents, water and acetonitrile, is reported herein. The solution thermodynamic functions were calculated from the experimental solubility data, using the van't Hoff and Gibbs equations, following the approach proposed by Krug et al. Thus, the solubility of ethylparaben is thermo-dependent, reaching its minimum value in pure water at 278.15 K and its maximum value in the cosolvent mixture w1 = 0.90 at 318.18 K. The enthalpy of solution is positive in all cases, which is an indication of the endothermic process, with an enthalpy-driven mixing process in mixtures rich in water and by entropy mixtures rich in acetonitrile.

The Dependence of Temperature and Composition on the Equilibrium Solubility and Thermodynamic Studies of Bioactive N-(9-Fluorenylmethoxycarbonyloxy)succinimide in Various Water–Cosolvent Mixtures

The equilibrium solubility of N-(9-fluorenylmethoxycarbonyloxy)succinimide in {dimethyl sulfoxide (DMSO), ethanol, ethylene glycol (EG), N,N-dimethylformamide (DMF)} plus water were determined by means of the isothermal equilibrium method at (283.15–328.15) K under atmosphere pressure. The measured values of N-(9-fluorenylmethoxycarbonyloxy)succinimide are positively increased with the increase of temperature in a certain cosolvent composition; however, that decreased when the content of water was gradually increasing and the largest solubility data was observed in pure DMF (0.04989 in mole fraction, 328.15 K). The mole fraction solubility in monosolvents ranked as DMF (9.693 × 10–3, 298.15 K) > DMSO (6.406 × 10–3, 298.15 K) > ethanol (8.237 × 10–4, 298.15 K) > EG (3.136 × 10–4, 298.15 K) > water (7.378 × 10–6). Under conditions of the same temperature and cosolvent composition, the solubility maximum of N-(9-fluorenylmethoxycarbonyloxy)succinimide was found in (DMF + water, 9.693 × 10–3 in mole fraction ...

Solubility of Genistin in Ethanol/Acetone + Water and Daidzein in Ethanol + Water Co-solvent Mixtures Revisited: IBKI Preferential Solvation Method

The preferential solvation parameters (δx1,3) of genistin in ethanol/acetone (1) + water (2) and daidzein in ethanol (1) + water (2) co-solvent mixtures at elevated temperatures were derived from available solubility data using the inverse Kirkwood–Buff integral method. The values of δx1,3 varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. For the three co-solvent mixtures, the values of δx1,3 were negative in water-rich mixtures, which indicated that daidzein or genistin was preferentially solvated by water and can act as Lewis bases to establish hydrogen bonds with the proton-donor functional groups of water (1). The same behavior was also observed for daidzein in ethanol (1) + water (2) and acetone (1) + water (2) mixtures with co-solvent-rich composition. For daidzein in ethanol (1) + water (2) mixtures with composition 0.24 < x1 < 1, and genistin in ethanol (1) + water (2) and acetone (1) + water (2) mixtures with intermediate compositions, the local mole fractions of ethanol or acetone were higher than those of the mixtures and therefore the δx1,3 values were positive, which indicated that genistin and daidzein were preferentially solvated by the co-solvent. In these regions, daidzein and genistin were acting as a Lewis acid with ethanol or acetone molecules.

Solubility of cetilistat in neat solvents and preferential solvation in (acetone, isopropanol or acetonitrile) + water co-solvent mixtures

The solubility of cetilistat in neat solvents of acetone, isopropanol, acetonitrile and water were determined experimentally by using the isothermal dissolution equilibrium method within the temperature range from (278.15 to 323.15) K under atmospheric pressure of 101.1kPa. At the fixed temperature, the mole fraction solubility of cetilistat was greater in acetone than in the other three neat solvents. They ranked as acetone>isopropanol>acetonitrile>water. The obtained solubilities were correlated with Apelblat equation. The largest value of relative average deviation was 0.86×10−2, and of root-mean-square deviation, 15.55×10−4. Furthermore, the preferential solvation parameters (δx1,3) of cetilistat in co-solvent mixtures of acetone (1)+water (2), isopropanol (1)+water (2) and acetonitrile (1)+water (2) were derived from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. The values of δx1,3 varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. The preferential solvation parameter was negative in water-rich mixtures but positive in intermediate composition and co-solvent-rich mixtures. In the latter case, it was conjecturable that cetilistat was acting as a Lewis acid with co-solvent molecules. The co-solvent action might be related to the breaking of the ordered structure of water around the polar moieties of cetilistat which increased the solvation of this drug. The solubility data and thermodynamic study expanded the physicochemical information about cetilistat in binary solvent mixtures, which was required in the pharmaceutical and chemical industries to save time and money in the optimization of the solubilization and/or crystallization process designs.

Predicting solvation free energies and thermodynamics in polar solvents and mixtures using a solvation-layer interface condition

We demonstrate that with two small modifications, the popular dielectric continuum model is capable of predicting, with high accuracy, ion solvation thermodynamics (Gibbs free energies, entropies, and heat capacities) in numerous polar solvents. We are also able to predict ion solvation free energies in water–co-solvent mixtures over available concentration series. The first modification to the classical dielectric Poisson model is a perturbation of the macroscopic dielectric-flux interface condition at the solute–solvent interface: we add a nonlinear function of the local electric field, giving what we have called a solvation-layer interface condition (SLIC). The second modification is including the microscopic interface potential (static potential) in our model. We show that the resulting model exhibits high accuracy without the need for fitting solute atom radii in a state-dependent fashion. Compared to experimental results in nine water–co-solvent mixtures, SLIC predicts transfer free energies to within 2.5 kJ/mol. The co-solvents include both protic and aprotic species, as well as biologically relevant denaturants such as urea and dimethylformamide. Furthermore, our results indicate that the interface potential is essential to reproduce entropies and heat capacities. These and previous tests of the SLIC model indicate that it is a promising dielectric continuum model for accurate predictions in a wide range of conditions.