Effect of K+ Force Fields on Ionic Conductivity and Charge Dynamics of KOH in Ethylene Glycol.

Predicting ionic conductivity is crucial for developing efficient electrolytes for energy storage and conversion and other electrochemical applications. An accurate estimate of ionic conductivity requires understanding complex ion-ion and ion-solvent interactions governing the charge transport at the molecular level. Molecular simulations can provide key insights into the spatial and temporal behavior of electrolyte constituents. However, such insights depend on the ability of force fields to describe the underlying phenomena. In this work, molecular dynamics simulations were leveraged to delineate the impact of force field parameters on ionic conductivity predictions of potassium hydroxide (KOH) in ethylene glycol (EG). Four different force fields were used to represent the K+ ion. Diffusion-based Nernst-Einstein and correlation-based Einstein approaches were implemented to estimate the ionic conductivity, and the predicted values were compared with experimental measurements. The physical aspects, including ion-aggregation, charge distribution, cluster correlation, and cluster dynamics, were also examined. A force field was identified that provides reasonably accurate Einstein conductivity values and a physically coherent representation of the electrolyte at the molecular level.

Mapping the frontier orbital energies of imidazolium-based cations using machine learning.

The knowledge of the frontier orbital, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), energies is vital for studying chemical and electrochemical stability of compounds, their corrosion inhibition potential, reactivity, etc. Density functional theory (DFT) calculations provide a direct route to estimate these energies either in the gas-phase or condensed phase. However, the application of DFT methods becomes computationally intensive when hundreds of thousands of compounds are to be screened. Such is the case when all the isomers for the 1-alkyl-3-alkylimidazolium cation [CnCmim]+ (n = 1-10, m = 1-10) are considered. Enumerating the isomer space of [CnCmim]+ yields close to 386 000 cation structures. Calculating frontier orbital energies for each would be computationally very expensive and time-consuming using DFT. In this article, we develop a machine learning model based on the extreme gradient boosting method using a small subset of the isomer space and predict the HOMO and LUMO energies. Using the model, the HOMO energies are predicted with a mean absolute error (MAE) of 0.4 eV and the LUMO energies are predicted with a MAE of 0.2 eV. Inferences are also drawn on the type of the descriptors deemed important for the HOMO and LUMO energy estimates. Application of the machine learning model results in a drastic reduction in computational time required for such calculations.

Macroscopic Differentiators for Microscopic Structural Nonideality in Binary Ionic Liquid Mixtures.

Combining two ionic liquids to form a binary ionic liquid mixture is a simple yet effective strategy to not only expand the number of ionic liquids but also precisely control various physicochemical properties of resultant ionic liquid mixtures. From a fundamental thermodynamic point of view, it is not entirely clear whether such mixtures can be classified as ideal solutions. Given a large number of binary ionic liquid mixtures that emerge, the ability to predict the presence of nonideality in such mixtures a priori without the need for experimentation or molecular simulation-based calculations is immensely valuable for their rational design. In this research report, we demonstrate that the difference in the molar volumes (ΔV) of the pure ionic liquids and the difference in the hydrogen-bonding ability of anions (Δß) are the primary determinants of nonideal behavior of binary ionic liquid mixtures containing a common cation and two anions. Our conclusion is derived from a comparison of microscopic structural properties expressed in terms of radial, spatial, and angular distributions for binary mixtures and those of the corresponding pure ionic liquids. Molecular dynamics simulations of 16 binary ionic liquid mixtures, containing a common cation 1-n-butyl-3-methylimidazolium [C4mim]+ and combinations of (less basic) fluorinated {trifluoromethylacetate [TFA]-, trifluoromethanesulfonate [TFS]-, bis(trifluoromethanesulfonyl)imide [NTf2]-, and tris (pentafluoroethyl) trifluorophosphate [eFAP]-} versus (more basic) nonfluorinated {chloride Cl-, acetate [OAC]-, methylsulfate [MeSO4]-, and dimethylphosphate [Me2PO4]-} anions, were conducted. The large number of binary ionic liquid mixtures examined here enabled us to span a broad range of ΔV and Δß values. The results indicate that binary mixtures of two ionic liquids for which ΔV > 60 cm3/mol and Δß > 0.4 are expected to be microscopically nonideal. On the other hand, ΔV < 60 cm3/mol and Δß < 0.4 will lead to molecular structures that are not differentiated from those of their pure ionic liquid counterparts.

Elucidating the effect of the ionic liquid type and alkyl chain length on the stability of ionic liquid-iron porphyrin complexes.

The present study is motivated by the long-term objective of understanding how ionic liquids are biodegraded by cytochrome P450, which contains iron porphyrin (FeP) serving as the catalytic center. To this end, the current study is designed to elucidate the impact of types and conformations of ionic liquids on the binding energy with FeP, the key interactions that stabilize the ionic liquid-FeP complex, and how the electron uptake ability of FeP is altered in the presence of ionic liquids. Four classes of ionic liquids are considered: 1-alkyl-3-methylimidazolium, 1-alkyl-pyridinium, 1-alkylsulfonium, and N-methyl-N-alkylpyrrolidinium. The influence of linear alkyl chains of ethyl, butyl, hexyl, octyl, and decyl is examined on the favorable binding modes with FeP, considering two widely different conformations: tail up and tail down with respect to FeP. Electronic structure calculations are performed at the M06 level of theory with the 6-31G(d,p) basis set for C, H, and N atoms, while the Lanl2DZ basis set is employed for Fe. Donor-acceptor interactions contributing to the binding of ionic liquids to FeP are unraveled through the natural bond orbital analysis. The results from this study indicate that the binding energies are dependent not only on the class of ionic liquids but also on the conformations presented to FeP. The propensity of FeP to acquire an electron is significantly enhanced in the presence of ionic liquid cations, irrespective of the type and the alkyl chain length.

Mesoscale Organization and Dynamics in Binary Ionic Liquid Mixtures.

The impact of mesoscale organization on dynamics and ion transport in binary ionic liquid mixtures is investigated by broad-band dielectric spectroscopy, dynamic-mechanical spectroscopy, X-ray scattering, and molecular dynamics simulations. The mixtures are found to form distinct liquids with macroscopic properties that significantly deviate from weighted contributions of the neat components. For instance, it is shown that the mesoscale morphologies in ionic liquids can be tuned by mixing to enhance the static dielectric permittivity of the resulting liquid by as high as 100% relative to the neat ionic liquid components. This enhancement is attributed to the intricate role of interfacial dynamics associated with the changes in the mesoscopic aggregate morphologies in these systems. These results demonstrate the potential to design the physicochemical properties of ionic liquids through control of solvophobic aggregation.

Insight into conformationally-dependent binding of 1-n-alkyl-3-methylimidazolium cations to porphyrin molecules using quantum mechanical calculations.

The first step in the biodegradation of imidazolium-based ionic liquids involves the insertion of the -OH group into the alkyl side chain, and it is believed to be triggered by cytochrome P450. However, at present, there is a lack of fundamental understanding of why the hydroxylation process is observed only for longer alkyl chain analogues. As the initial step of the hydroxylation reaction involves the ionic liquid binding to Fe-porphyrin (FeP) - the catalytic center of cytochrome P450, the orientation of ionic liquids presented to FeP is expected to play a crucial role in eventual hydroxylation of the alkyl side chain. In order to elucidate the chain-length dependent binding preferences exhibited by the homologous series of 1-n-alkyl-3-methylimidazolium (n = 2, 4, 6, 8, and 10) [Cnmim]+ cations, a quantum mechanical treatment of the cations in the presence of free base porphyrin (FBP) and FeP is carried out at the B3LYP-D2 and M06 levels. The binding energy of different complexes with FBP and FeP is investigated by considering three vastly different starting relative orientations of the cations with respect to FBP and FeP: tail down, tail up, and interplanar. Our calculations of binding energies reveal that the cation orientations initiated from the tail down conformations (alkyl chain facing the porphyrin molecules) are progressively destabilized as the alkyl chain length increases. The decomposition of the binding energies into various energetic contributions shows that the interaction energy between the cations and porphyrin molecules varies with the cation geometries presented to porphyrin molecules and is the primary determinant of the magnitude of the binding energies. We further demonstrate that the propensity of the cation-FeP complexes to acquire an electron, the next step in the hydroxylation reaction cycle upon substrate binding, is favored independent of the cations and conformations, suggesting that this step is not the reason for the low biodegradability of short alkyl chain bearing cations. Furthermore, the weaker binding of the ionic liquid to FeP is anticipated to facilitate dioxygen binding to FeP, the step following the electron transfer reaction. Overall, the results of the present calculations indicate that the destabilization of the tail down conformations relative to the other two conformations correlates with the experimental results of the chain length-dependent biodegradation of imidazolium-based ionic liquids.

Molecular Origins of the Apparent Ideal CO2 Solubilities in Binary Ionic Liquid Mixtures.

Molecular dynamics (MD) simulations were conducted to investigate the variation of Henry's constant of CO2 in two binary ionic liquid mixtures. One of the mixtures is formed by pairing the cation 1- n-butyl-3-methylimidazolium [C4mim]+ with chloride Cl- and methylsulfate [MeSO4]-, whereas the other binary ionic liquid mixture contains [C4mim]+ in combination with the anions Cl- and bis(trifluoromethanesulfonyl)imide [NTf2]-. In order to provide a microscopic understanding of the behavior of the Henry's constant with the anion composition, MD simulations of ionic liquid mixtures with and without CO2 saturation were performed at 353 K and 10 bar. Our calculations indicate that the Henry's constant for CO2 follows a highly nonlinear, although expected based on ideal solubility, trend with respect to the increasing concentration of Cl- in [C4mim]Cl x[NTf2]1- x, whereas the Henry's constant is almost independent of the anion composition in the [C4mim]Cl x[MeSO4]1- x system. Structural analyses presented in terms of radial, spatial, and angular distribution functions point to significant structural reorganization of the anions around cations in the [C4mim]Cl x[NTf2]1- x system. Because of the weakly coordinating ability of the [NTf2]- anion with the cation, the [NTf2]- anion is displaced from the equatorial plane of the imidazolium ring and occupies positions above and below the ring, enabling enhanced CO2-[NTf2]- association. The rearrangement also weakens the cation π-π interactions, resulting in the formation of increased local free volume aiding CO2 accommodation. On the contrary, such structural transitions are absent in the [C4mim]Cl x[MeSO4]1- x mixture system.

Globular, Sponge-like to Layer-like Morphological Transition in 1-n-Alkyl-3-methylimidazolium Octylsulfate Ionic Liquid Homologous Series.

Segregation of polar and nonpolar domains in ionic liquids for which either the cation or anion is responsible for inducing nonpolar domains is well understood. On the other hand, information regarding the nanoscale heterogeneities originating due to the presence of nonpolar content on both the ions is rudimentary at this point. The present contribution is aimed at addressing this question and focuses on a molecular dynamics simulation study to probe nanoscale structural and aggregation features of the 1-n-alkyl-3-methylimidazolium [Cnmim] octylsulfate [C8SO4] ionic liquid homologous series (n = 2, 4, 6, 8, 10, and 12). The objective of this work is to determine the effect of increasing alkyl chain length in the cation on nonpolar domain formation, especially when the alkyl chain lengths from both the ions participate in defining such domains. The results indicate that all the ionic liquids form nonpolar domains, morphology of which gradually changes from globular, sponge-like to layer-like structure with increase in the cationic alkyl chain length. The length of the nonpolar domains calculated from the total structure factor for [C10mim][C8SO4] is considerably higher than that reported for other imidazolium-based ionic liquid containing smaller anions. The structure factor for [C12mim][C8SO4] ionic liquid contains multiple intermediate peaks separating the charge alternation peak and pre-peak, which points to nonpolar domains of varying lengths, an observation that remains to be validated. Analysis of the heterogeneous order parameters and orientational correlation functions of the alkyl chains further suggests an increase in the spatial heterogeneity and long-range order along the homologous series. The origin of rich diversity of structures obtained by introducing nonpolar content on both the ions is discussed.

Cassandra: An open source Monte Carlo package for molecular simulation.

Cassandra is an open source atomistic Monte Carlo software package that is effective in simulating the thermodynamic properties of fluids and solids. The different features and algorithms used in Cassandra are described, along with implementation details and theoretical underpinnings to various methods used. Benchmark and example calculations are shown, and information on how users can obtain the package and contribute to it are provided. © 2017 Wiley Periodicals, Inc.

Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach.

Ionic liquids (ILs) are salts that remain liquid down to low temperatures, and sometimes well below room temperature. ILs have been called "green solvents" because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy, and molecular simulations reveal that IL cations nucleate morphological defects in the microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in, and ultimately disrupt, the cell membrane.

Molecular dynamics simulation study of the association of lidocainium docusate and its derivatives in aqueous solution.

Ionic liquid active pharmaceutical ingredients (IL APIs) are novel materials in which the ions themselves are APIs, but the pure salt is a liquid under ambient conditions. It has been found that IL APIs can have superior performance relative to their conventional salt analogues, but the mechanism for this is unclear. We have used molecular simulations to estimate the aqueous phase association constants of the IL API lidocainium docusate and their sodium and chloride counterparts. Lidocainium is the cationic form of lidocaine, a local anesthetic, while the docusate anion is an emollient. From strongest to weakest, the calculated association constants are 10.1 M(-1) (lidocainium docusate); 0.77 M(-1) (sodium chloride); 0.086 M(-1) (sodium docusate); and 0.065 M(-1) (lidocainium chloride). These results suggest that the experimentally observed enhanced efficacy of lidocainium docusate relative to the traditional drug formulation as a lidocaine hydrochloride salt could result from association of the ions in aqueous solution and at the cell membrane, leading to a synergistic activity effect.

Amphiphilic interactions of ionic liquids with lipid biomembranes: a molecular simulation study.

Current bottlenecks in the large-scale commercial use of many ionic liquids (ILs) include their high costs, low biodegradability, and often unknown toxicities. As a proactive effort to better understand the molecular mechanisms of ionic liquid toxicities, the work herein presents a comprehensive molecular simulation study on the interactions of 1-n-alkyl-3-methylimidazolium-based ILs with a phosphatidylcholine (PC) lipid bilayer. We explore the effects of increasing alkyl chain length (n = 4, 8, and 12) in the cation and anion hydrophobicity on the interactions with the lipid bilayer. Bulk atomistic molecular dynamics (MD) simulations performed at millimolar (mM) IL concentrations show spontaneous insertion of cations into the lipid bilayer regardless of the alkyl chain length and a favorable orientational preference once a cation is inserted. Cations also exhibit the ability to "flip" inside the lipid bilayer (as is common for amphiphiles) if partially inserted with an unfavorable orientation. Moreover, structural analysis of the lipid bilayer show that cationic insertion induces roughening of the bilayer surface, which may be a precursor to bilayer disruption. To overcome the limitation in the timescale of our simulations, free energies for a single IL cation and anion insertion have been determined based on potential of mean force calculations. These results show a decrease in free energy in response to both short and long alkyl chain IL cation insertion, and likewise for a single hydrophobic anion insertion, but an increase in free energy for the insertion of a hydrophilic chloride anion. Both bulk MD simulations and free energy calculations suggest that toxicity mechanisms toward biological systems are likely caused by ILs behaving as ionic surfactants. [Yoo et al., Soft Matter, 2014].

State of hydrophobic and hydrophilic ionic liquids in aqueous solutions: are the ions fully dissociated?

Molecular dynamics simulations were performed for aqueous solutions of five ionic liquids (ILs): 1-ethyl-3-methylimidazolium ([C2mim]) bis(trifluoromethanesulfonyl) imide ([NTf2]), 1-n-butyl-3-methylimidazolium ([C4mim]) [NTf2], 1-n-hexyl-3-methylimidazolium ([C6mim]) [NTf2], [C2mim] ethylsulfate ([C2H5SO4]), and [C2mim] chloride (Cl) to determine whether the ions of these ILs are associated at relatively high dilutions and whether the association is governed by hydrophobicity/hydrophilicity of the ILs. The adaptive biasing force technique was applied to calculate the potential of mean force (PMF) for each IL ion pair. For all of the ILs, the PMF is characterized by two distinct contact minima in which the ions have different relative conformations. The hydrophobic ILs bearing the anion [NTf2](-) exist predominantly in the associative state; the strength of the association of these ILs increases with increase in the alkyl chain length. The most hydrophilic IL [C2mim] Cl was determined to be almost fully dissociated at the concentration examined in the study. [C2mim] [C2H5SO4] showed hydration behavior that was intermediate between that exhibited by the ILs in which the anion is substituted with either Cl(-) or [NTf2](-) paired with [C2mim](+). Association constants for these ILs were also computed. Radial distribution functions calculated by constraining the ions at the contact minima showed that hydration of the anion plays the dominant role in determining the microscopic behavior of these ILs in aqueous solutions.

A comparison of the solvation thermodynamics of amino acid analogues in water, 1-octanol and 1-n-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids by molecular simulation.

A computational approach is developed to quantitatively study the solvation thermodynamics of amino acid analogues in ionic liquids via molecular simulation. The solvation thermodynamics of amino acid analogues in ionic liquids is important for an understanding of protein-ionic liquid interactions, shedding insight into the structure and solubility of proteins, and the activity of enzymes in ionic liquids. This information is additionally key to developing novel extraction processes. As a result of the challenge of quantitatively describing the solvation behavior of ionic liquids, a key outcome of the present study is the development of a "hydrophobicity" scale to quantitatively describe the amino acid analogues. The scale allows one to separate the results of both the hydrophobic and hydrophillic analogues, simplifying an understanding of the observed trends. Equipped with the proposed hydrophobicity scale, one needs only perform conventional solvation free energy calculations of the amino acid analogues in the ionic liquids of interest. The necessary simulation tools are available in most open-source simulation software, facilitating the adoption of this approach by the simulation community at large. We have studied the case of varying the cation alkyl-chain length of a 1-n-alkyl-3-methylimidazolium cation paired with the bis(trifluoromethylsulfonyl)imide anion. The findings suggest that a judicious selection of both the cation and anion could potentially lead to a solvent for which the amino acid analogues have an affinity far greater than that for both water and a non-polar reference solvent.

Combined application of high-field diffusion NMR and molecular dynamics simulations to study dynamics in a mixture of carbon dioxide and an imidazolium-based ionic liquid.

Self-diffusion and related short-time dynamic and structural properties were investigated for mixtures of carbon dioxide and the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [bmim](+)[Tf2N](-) for a broad range of carbon dioxide molar fractions and at different temperatures. The studies were performed by a novel multinuclear pulsed field gradient (PFG) NMR technique, which combines the advantages of a high magnetic field (17.6 T) and a high magnetic field gradient (up to 30 T/m), in combination with molecular dynamics simulations. In general, a satisfactory agreement was observed between the experimental and simulation diffusion data. Under all conditions examined, the self-diffusion coefficients of carbon dioxide were found to be approximately an order of magnitude larger than the corresponding self-diffusion coefficients of the ions. It was observed that an increase in temperature and in the amount of carbon dioxide in the ionic liquid led to an increase in the ion self-diffusivities without changing the relationship between the self-diffusion coefficients of the cations and anions. An observation of a slightly higher diffusivity of the cations in comparison to that of the anions is attributed to the preferential mobility of the cations in the direction of the ring plane. The diffusion activation energies of the ions were found to decrease gradually with an increase of the carbon dioxide content in the ionic liquid. The activation energy of the carbon dioxide diffusion in all cases was found to be smaller than those of the ions.

A general and efficient Monte Carlo method for sampling intramolecular degrees of freedom of branched and cyclic molecules.

A simple and easily implemented Monte Carlo algorithm is described which enables configurational-bias sampling of molecules containing branch points and rings with endocyclic and exocyclic atoms. The method overcomes well-known problems associated with sequential configurational-bias sampling methods. A "reservoir" or "library" of fragments are generated with known probability distributions dependent on stiff intramolecular degrees of freedom. Configurational-bias moves assemble the fragments into whole molecules using the energy associated with the remaining degrees of freedom. The methods for generating the fragments are validated on models of propane, isobutane, neopentane, cyclohexane, and methylcyclohexane. It is shown how the sampling method is implemented in the Gibbs ensemble, and validation studies are performed in which the liquid coexistence curves of propane, isobutane, and 2,2-dimethylhexane are computed and shown to agree with accepted values. The method is general and can be used to sample conformational space for molecules of arbitrary complexity in both open and closed statistical mechanical ensembles.

Water coordination structures and the excess free energy of the liquid.

We assess the contribution of each coordination state to the hydration free energy of a distinguished water molecule, the solute water. We define a coordination sphere, the inner-shell, and separate the hydration free energy into packing, outer-shell, and local, solute-specific (chemical) contributions. The coordination state is defined by the number of solvent water molecules within the coordination sphere. The packing term accounts for the free energy of creating a solute-free coordination sphere in the liquid. The outer-shell contribution accounts for the interaction of the solute with the fluid outside the coordination sphere and it is accurately described by a Gaussian model of hydration for coordination radii greater than the minimum of the oxygen-oxygen pair-correlation function: theory helps identify the length scale to parse chemical contributions from bulk, nonspecific contributions. The chemical contribution is recast as a sum over coordination states. The nth term in this sum is given by the probability p(n) of observing n water molecules inside the coordination sphere in the absence of the solute water times a factor accounting for the free energy, W(n), of forming an n-water cluster around the solute. The p(n) factors thus reflect the intrinsic properties of the solvent while W(n) accounts for the interaction between the solute and inner-shell solvent ligands. We monitor the chemical contribution to the hydration free energy by progressively adding solvent ligands to the inner-shell and find that four-water molecules are needed to fully account for the chemical term. For a chemically meaningful coordination radius, we find that W(4) ≈ W(1) and thus the interaction contribution is principally accounted for by the free energy for forming a one-water cluster, and intrinsic occupancy factors alone account for over half of the chemical contribution. Our study emphasizes the need to acknowledge the intrinsic solvent properties in interpreting the hydration structure of any solute, with particular care in cases where the solute-solvent interaction strength is similar to that between the solvent molecules.

Efficient Solvation Free Energy Calculations of Amino Acid Analogs by Expanded Ensemble Molecular Simulation.

We present an efficient, automated expanded ensemble method to calculate the residual chemical potential or solvation free energy by molecular dynamics simulation. The methodology is validated by computing the residual chemical potential of 13 amino acid analogs in water at 300 K and 1 bar and comparing to reference simulation data. Overall agreement is good, with the methodology of the present study reaching limiting precisions of less than 0.1 kBT in half of the total simulation time of the reference simulation study which utilized Bennett's acceptance ratio method. The apparent difference in the efficiencies is a result of the inherent advantages of the expanded ensemble method, which creates an improved decorrelation of simulation data and improves the sampling of the important regions of the configurational phase space of each subensemble. The present adaptation utilizes histograms of proposed transition energies collected throughout the entire simulation, to make extremely precise calculations of the relative free energy between neighboring subensembles.

A method for computing the solubility limit of solids: application to sodium chloride in water and alcohols.

We present an adaptable method to compute the solubility limit of solids by molecular simulation, which avoids the difficulty of reference state calculations. In this way, the method is highly adaptable to molecules of complex topology. Results are shown for solubility calculations of sodium chloride in water and light alcohols at atmospheric conditions. The pseudosupercritical path integration method is used to calculate the free energy of the solid and gives results that are in good agreement with previous studies that reference the Einstein crystal. For the solution phase calculations, the self-adaptive Wang-Landau transition-matrix Monte Carlo method is used within the context of an expanded isothermal-isobaric ensemble. The method shows rapid convergence properties and the uncertainty in the calculated chemical potential was 1% or less for all cases. The present study underpredicts the solubility limit of sodium chloride in water, suggesting a shortcoming of the molecular models. Importantly, the proper trend for the chemical potential in various solvents was captured, suggesting that relative solubilities can be computed by the method.

1H NMR and molecular dynamics evidence for an unexpected interaction on the origin of salting-in/salting-out phenomena.

By employing (1)H NMR spectroscopy and molecular simulations, we provide an explanation for recent observations that the aqueous solubilities of ionic liquids exhibit salting-out to salting-in regimes upon addition of distinct inorganic salt ions. Using a typical ionic liquid [1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide], we observed the existence of preferential specific interactions between the low electrical charge density ("apolar moiety") parts of the ionic liquid cation and the inorganic salts. These a priori unexpected interactions become increasingly favorable as one moves from salting-out to salting-in effects. More specifically, this interpretation is validated by distinct aqueous solution (1)H NMR data shifts in the ionic liquid cation upon inorganic salt addition. These shifts, which are well noted in the terminal and preterminal hydrogens of the alkyl chain appended to the imidazolium ring, correlate quantitatively with solubility data, both for cases where the nature of inorganic salt is changed, at constant concentration, and for those where the concentration of a given inorganic salt is varied. Molecular simulations have also been performed permitting us to garner a broader picture of the underlying mechanism and structure of this complex solvation phenomenon. These findings can now be profitably used to anticipate solution behavior upon inorganic salt addition well beyond the specificity of the ionic liquid solutions, i.e., for a diversity of distinct solutes differing in chemical nature.