Why the partition coefficient of ionic liquids is concentration-dependent.

The partition coefficient of a substance measures its solubility in octanol compared with water and is widely used to estimate toxicity. If a substance is hardly soluble in octanol, then it is practically impossible for it to enter (human) cells and therefore is less likely to be toxic. For novel drugs it might be important to penetrate the cell through the membrane or even integrate into it. While for most simple substances the partition coefficient is concentration-independent at low concentrations, this is not true for a few important classes of complex molecules, such as ionic liquids or tensides. We present a simple association-dissociation model for concentration dependence of the partition coefficient of ionic liquids. Atomistic computer simulations serve to parametrize our model by calculating solvation free energies in water and octanol using thermodynamic integration. We demonstrate the validity of the method by reproducing the concentration-independent partition coefficients of small alcohols and the concentration-dependent partition coefficient of a commonly used ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [C4MIM][NTf2]. The concentration dependence is accurately predicted in a concentration range of several orders of magnitude.

Comparison of force fields on the basis of various model approaches--how to design the best model for the [CnMIM][NTf2] family of ionic liquids.

In this contribution, we present two new united-atom force fields (UA-FFs) for 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [C(n)MIM][NTf(2)] (n=1, 2, 4, 6, 8) ionic liquids (ILs). One is parametrized manually, and the other is developed with the gradient-based optimization workflow (GROW). By doing so, we wanted to perform a hard test to determine how researchers could benefit from semiautomated optimization procedures. As with our already published all-atom force field (AA-FF) for [C(n)MIM][NTf(2)] (T. Köddermann, D. Paschek, R. Ludwig, ChemPhysChem- 2007, 8, 2464), the new force fields were derived to fit experimental densities, self-diffusion coefficients, and NMR rotational correlation times for the IL cation and for water molecules dissolved in [C(2)MIM][NTf(2)]. In the manual force field, the alkyl chains of the cation and the CF3 groups of the anion were treated as united atoms. In the GROW force field, only the alkyl chains of the cation were united. All other parts of the structures of the ions remained unchanged to prevent any loss of physical information. Structural, dynamic, and thermodynamic properties such as viscosity, cation rotational correlation times, and heats of vaporization calculated with the new force fields were compared with values simulated with the previous AA-FF and the experimental data. All simulated properties were in excellent agreement with the experimental values. Altogether, the UA-FFs are slightly superior for speed-up reasons. The UA-FF speeds up the simulation by about 100 % and reduces the demanded disk space by about 78 %. More importantly, real time and efforts to generate force fields could be significantly reduced by utilizing GROW. The real time for the GROW parametrization in this work was 2 months. Manual parametrization, in contrast, may take up to 12 months, and this is, therefore, a significant increase in speed, though it is difficult to estimate the duration of manual parametrization.

The effect of neutral ion aggregate formation on the electrical conductivity of an ionic liquid and its mixtures with chloroform.

We have studied the electrical conductivity of mixtures of the ionic liquid (IL) [C(2)mim][NTf(2)] with chloroform for various concentrations at a temperature of 303 K by both experiments and MD simulations. The molar conductivities exhibit an initial increase with decreasing IL concentration, which again sharply decreases in the region of highly diluted IL concentrations. This behavior is according to a competition between 1) the decreasing viscosity with increasing chloroform concentration due to fluidizing the mixture, and 2) the decreasing amount of charge carriers due to the formation of neutral IL aggregates. The simulated molar conductivities and their concentration dependence are found to be in reasonable agreement with the experimentally determined values, suggesting that essential correlations between the solvated ionic species in the solution are well represented. Both experiments and simulations show that the Nernst-Einstein relation drastically overestimates the conductivity of the solutions at low IL concentrations. According to our MD simulation data, this observation is due to the extensive formation of neutral aggregates in the low-concentration regime.

What far-infrared spectra can contribute to the development of force fields for ionic liquids used in molecular dynamics simulations.

Symbiosis: Far-infrared spectra can be used to check the quality of force fields for molecular dynamics simulations of ionic liquids. On the other hand, MD simulations can explain the molecular basis of measured properties for this new liquid material (see picture).

On the validity of Stokes-Einstein and Stokes-Einstein-Debye relations in ionic liquids and ionic-liquid mixtures.

Stokes-Einstein (SE) and Stokes-Einstein-Debye (SED) relations in the neat ionic liquid (IL) [C(2)mim][NTf(2)] and IL/chloroform mixtures are studied by means of molecular dynamics (MD) simulations. For this purpose, we simulate the translational diffusion coefficients of the cations and anions, the rotational correlation times of the C(2)--H bond in the cation C(2)mim(+), and the viscosities of the whole system. We find that the SE and SED relations are not valid for the pure ionic liquid, nor for IL/chloroform mixtures down to the miscibility gap (at 50 wt % IL). The deviations from both relations could be related to dynamical heterogeneities described by the non-Gaussian parameter alpha(t). If alpha(t) is close to zero, at a concentration of 1 wt % IL in chloroform, both relations become valid. Then, the effective radii and volumes calculated from the SE and SED equations can be related to the structures found in the MD simulations, such as aggregates of ion pairs. Overall, similarities are observed between the dynamical properties of supercooled water and those of ionic liquids.

Solvophobic solvation and interaction of small apolar particles in imidazolium-based ionic liquids.

We report results of molecular dynamics simulations characterizing the solvation and interaction of small apolar particles such as methane and xenon in imidazolium-based ionic liquids (ILs). The simulations are able to reproduce semiquantitatively the anomalous temperature dependence of the solubility of apolar particles in the infinite dilution regime. We observe that the "solvophobic solvation" of small apolar particles in ILs is governed by compensating entropic and enthalpic contributions, very much like the hydrophobic hydration of small apolar particles in liquid water. In addition, our simulations clearly indicate that the solvent mediated interaction of apolar particles dissolved in ILs is similarly driven by compensating enthalpic and entropic contributions, making the "solvophobic interaction" thermodynamically analogous to the hydrophobic interaction.

Ionic liquids: dissecting the enthalpies of vaporization.

We calculate the heats of vaporisation for imidazolium-based ionic liquids [C(n)mim][NTf(2)] with n=1, 2, 4, 6, 8 by means of molecular dynamics (MD) simulations and discuss their behavior with respect to temperature and the alkyl chain length. We use a force field developed recently. The different cohesive energies contributing to the overall heats of vaporisations are discussed in detail. With increasing alkyl chain length, the Coulomb contribution to the heat of vaporisation remains constant at around 80 kJ mol(-1), whereas the van der Waals interaction increases continuously. The calculated increase of about 4.7 kJ mol(-1) per CH(2)-group of the van der Waals contribution in the ionic liquid exactly coincides with the increase in the heats of vaporisation for n-alcohols and n-alkanes, respectively. The results support the importance of van der Waals interactions even in systems completely composed of ions.

Molecular dynamic simulations of ionic liquids: a reliable description of structure, thermodynamics and dynamics.

The parameterization of a new force-field and its validation for the liquid description of five imidazolium-based ionic liquids [C(n)mim][NTf2] (n=1,2,4,6,8) are described. The proposed force-field is derived to reproduce densities, self-diffusion coefficients for cations and ions as well as NMR rotational correlation times for cations and water molecules in [C(2)mim][NTf2]. The temperature dependence and the cation chain-length dependence of these properties is described well. Very good agreement between simulated and experimental values for the heats of vaporization, shear viscosities and NMR rotational correlation times is also achieved. All properties are crucial for understanding the nature and interaction of ionic liquids. The good performance of the new force-field suggests that the Lennard-Jones interactions previously were strongly overestimated. The given force-field now allows us to investigate other important properties of this class of ionic liquids such as the micro segregation of ionic liquids, ion pair formation, lifetimes of ion pairs and the solvent dependency of these properties.

Ion-pair formation in the ionic liquid 1-ethyl-3-methylimidazolium bis(triflyl)imide as a function of temperature and concentration.

The structures and ion-pair formation in the ionic liquid (IL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide are studied by a combination of FTIR measurements and DFT calculations. We could clearly distinguish imidazolium cations that are completely H-bonded to anions from those that are single H-bonded in ion pairs. Ion-pair formation already occurs in the neat IL and rises with temperature. Ion-pair formation is strongly promoted by dilution of the IL in chloroform. In these weakly polar environments ion pairs H-bonded via C(2)H are strongly favored over those H-bonded via C(4,5)H. This finding is in agreement with DFT (gas phase) calculations, which show a preference for ion pairs H-bonded via C(2)H as a result of the acidic C(2)H bond.