Explicit solvation thermodynamics in ionic solution: extending grid inhomogeneous solvation theory to solvation free energy of salt–water mixtures

Hydration thermodynamics play a fundamental role in fields ranging from the pharmaceutical industry to environmental research. Numerous methods exist to predict solvation thermodynamics of compounds ranging from small molecules to large biomolecules. Arguably the most precise methods are those based on molecular dynamics (MD) simulations in explicit solvent. One theory that has seen increased use is inhomogeneous solvation theory (IST). However, while many applications require accurate description of salt–water mixtures, no implementation of IST is currently able to estimate solvation properties involving more than one solvent species. Here, we present an extension to grid inhomogeneous solvation theory (GIST) that can take salt contributions into account. At the example of carbazole in 1 M NaCl solution, we compute the solvation energy as well as first and second order entropies. While the effect of the first order ion entropy is small, both the water–water and water–ion entropies contribute strongly. We show that the water–ion entropies are efficiently approximated using the Kirkwood superposition approximation. However, this approach cannot be applied to the water–water entropy. Furthermore, we test the quantitative validity of our method by computing salting-out coefficients and comparing them to experimental data. We find a good correlation to experimental salting-out constants, while the absolute values are overpredicted due to the approximate second order entropy. Since ions are frequently used in MD, either to neutralize the system or as a part of the investigated process, our method greatly extends the applicability of GIST. The use-cases range from biopharmaceuticals, where many assays require high salt concentrations, to environmental research, where solubility in sea water is important to model the fate of organic substances.

Predicting Solvation Thermodynamics in Water and Ionic Liquids using the Multi-Scale Solvation Layer Interface Condition (SLIC)

We highlight the most recent developments of the solvation-layer interface condition (SLIC) continuum dielectric model in predicting solvation thermodynamics of neutral small molecules in water and multiple ionic liquids. We demonstrate that a simple temperature-dependent solvent-accessible-surface-area (SASA) correlation and a cavity-dispersion-combinatorial (CDC) theory, combined with the SLIC electrostatics model, provide highly accurate predictions of Gibbs solvation energies, solvation entropies, and solvation heat capacities. The SLIC/SASA model parameters are temperature dependent, whereas the SLIC/CDC parameters are constant. To address the lack of experimental data pertaining to the accuracy of the models, we conducted an extensive literature search and data compilation to obtain credible experimental solvation data. This yielded 159 and 123 data points for hydration entropies and heat capacities of neutral small molecules, respectively. Compared to experimental data, the SLIC/SASA and SLIC/CDC models, respectively, achieve an RMS error 1.39 (1.24) and 1.15 (1.76) kcal/mol for hydration free energy (hydration entropy) predictions. Solvation heat capacities are predicted with RMS errors 24.42 and 46.17 cal/mol/K. Most remarkably, the SLIC/CDC predictions of solvation entropies and heat capacities are made without apriori knowledge of experimental solvation entropies. In addition, the SLIC/SASA predictions of Gibbs solvation energies (solvation entropies) of 12 amino acid side-chain analogs in seven (three) ionic liquids are compared to the available explicit-solvent simulation data from Paluch et al.~\cite{Paluch12} and Latif~\cite{Latif14} et al.

FORMAÇÃO DE AZEÓTROPOS DO PONTO DE VISTA DA TERMODINÂMICA DE SOLVATAÇÃO

FORMATION OF AZEOTROPES FROM THE STANDPOINT OF SOLVATION THERMODYNAMICS. The formation of azeotropes is related to the deviation of the ideality of liquid mixtures. This deviation is expressed by the activity coefficient of each component. However, the physical origin of this behavior is not well quantified in terms of molecular interactions. In this work, a regular solution model was used, relating the β parameter to the solvation free energy of pure liquids in themselves and in the other component. A mathematical expression was derived that indicates when an azeotrope is formed. This equation shows that the greater the difference in vapour pressure between components, the greater the solvation difference of each liquid in itself and in the other component is needed to form the azeotrope. A set of 10 mixtures were randomly chosen and investigated as a test, and the equation worked in all cases.