In this paper we have investigated via experimental and simulations techniques the transport properties, in terms of total ionic conductivity and ion diffusion coefficients, of ionic liquids and

Low concentrated aqueous ionic liquids (ILs) and their influence on protein structures have attracted a lot of interest over the last few years. This can be mostly attributed to the fact that aqueous ILs, depending on the ion species involved, can be used as protein protectants or protein denaturants. Atomistic molecular dynamics (MD) simulations are performed in order to study the influence of different aprotic ILs on the properties of a short hairpin peptide. Our results reveal distinct binding and denaturation effects for 1-ethyl-3-methylimidazolium (EMIM) in combination with different anions, namely, chloride (CL), tetrafluoroborate (BF4) and acetate (ACE). The simulation outcomes demonstrate that the studied ILs with larger anions reveal a more pronounced accumulation behavior of the individual ion species around the peptide, which is accomplished by a stronger dehydration effect. We can relate these findings to the implications of the Kirkwood-Buff theory, which provides a thermodynamic explanation for the denaturation strength in terms of the IL accumulation behavior. The results for the spatial distribution functions, the binding energies and the local/bulk partition coefficients are in good agreement with metadynamics simulations in order to determine the energetically most stable peptide conformations. The free energy landscapes indicate a decrease of the denaturation strength in the order EMIM/ACE, EMIM/BF4 and EMIM/CL, which coincides with a decreasing size of the anion species. An analysis of the potential binding energies reveals that this effect is mainly of enthalpic nature.

We studied the stability of a small β-hairpin peptide under the influence of an aqueous 1-ethyl-3-methylimidazolium acetate ([EMIM](+)[ACE](-)) solution via all-atom molecular dynamics simulations in combination with metadynamics. Our free energy results indicate a denaturation of the peptide structure in the presence of the ionic liquid which is validated by a significant broadening of the end-to-end distance. The radial distribution functions between the ions and the peptide were used for the calculation of the preferential binding coefficients in terms of the Kirkwood-Buff theory. A significant structure dependent binding behavior of acetate to the peptide was found which can be interpreted as the main reason for the denaturation of the native conformation. The outcomes of our simulations allow us to propose a simple mechanism to explain the unfolding of the peptide with regard to the specific properties of ionic liquids. Our results are in good agreement with experimental findings and demonstrate the benefits of ionic liquids as tunable co-solutes with regard to their influence on protein structural properties.

We study the solvation properties of the ionic liquid 1-ethyl-3-methylimidazolium acetate ([EMIM](+)[ACE](-)) and the resulting dynamic behavior for differently charged model solutes at room temperature via atomistic molecular dynamics (MD) simulations of 300 ns length and 200 ns equilibration time. The solutes are simple model spheres which are either positively or negatively charged with a valency of one, or uncharged. The numerical findings indicate a distinct solvation behavior with the occurrence of well-pronounced solvation shells whose composition significantly depends on the charge of the solute. All the results of our simulations evidence the existence of a long-range perturbation effect in presence of the solutes. Our findings validate the dominance of electrostatic interactions with regard to unfavorable entropic ordering effects which elucidates the enthalpic character of the solvation process in ionic liquids for charged solutes.

4,5-Dialkylated imidazolium lipid salts are a new class of lipid analogues showing distinct biological activities. The potential effects of the imidazolium lipids on artificial lipid membranes and the corresponding membrane interactions was analyzed. Therefore, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was employed to create an established lipid monolayer model and a bilayer membrane. Mixed monolayers of DPPC and 4,5-dialkylimidazolium lipids differing by their alkyl chain length (C, C, and C) were characterized by surface pressure-area (π-A) isotherms using a Wilhelmy film balance in combination with epifluorescence microscopy. Monolayer hysteresis for binary mixtures was examined by recording triplicate consecutive compression-expansion cycles. The lipid miscibility and membrane stability of DPPC/imidazolium lipids were subsequently evaluated by the excess mean molecular area (ΔA) and the excess Gibbs free energy (ΔG) of mixing. Furthermore, the thermotropic behavior of mixed liposomes of DPPC/imidazolium lipids was investigated by differential scanning calorimetry (DSC). The C-imidazolium lipid (C-IMe·HI) forms a thermodynamically favored and kinetically reversible Langmuir monolayer with DPPC and exhibits a rigidification effect on both DPPC monolayer and bilayer structures at low molar fractions (X ≤ 0.3). However, the incorporation of the C-imidazolium lipid (C-IMe·HI) causes the formation of an unstable and irreversible Langmuir-Gibbs monolayer with DPPC and disordered DPPC liposomes. The C-imidazolium lipid (C-IMe·HI) displays negligible membrane activity. To better understand these results on a molecular level, all-atom molecular dynamics (MD) simulations were performed. The simulations yield two opposing molecular mechanisms governing the different behavior of the three imidazolium lipids: a lateral ordering effect and a free volume/stretching effect. Overall, our study provides the first evidence that the membrane interaction of the C and C derivatives modulates the structural organization of lipid membranes. On the contrary, for the C derivative its membrane activity is too low to contribute to its earlier reported potent cytotoxicity.

The dynamical and structural properties in two ionic liquid electrolytes (ILEs) based on 1-ethyl-3-methylimidazolium bis-(trifluoromethanesulfonyl)-imide ([emim][TFSI]) and N-methyl-N-propylpyrrolidinium bis-(trifluoromethanesulfonyl)imide([pyr13][TFSI]) were compared as a function of lithium bis-(trifluoromethanesulfonyl)-imide (LiTFSI) salt concentrations using atomistic molecular dynamics (MD) simulations. The many-body polarizable APPLE&P force field has been utilized. The influence of anion polarization on the structure of the first coordination shell of Li(+) was examined. In particular, the reduction of the oxygen of the TFSI anion (OTFSI) polarizability from 1.36 Å(3) to 1.00 Å(3) resulted in an increased fraction of the TFSI anion bidentate coordination to the Li(+). While the overall dynamics in [pyr13][TFSI]-based ILEs was slower than in [emim][TFSI]-based ILEs, the exchange of TFSI anions in and out of the first coordination shell of Li(+) was found to be faster in pyr13-based systems. The Li(+) ion transference number is higher for these systems as well. These trends can be related to the difference in interaction of TFSI with the IL cation which is stronger for pyr13 than for emim.

Classical Molecular Dynamics simulations describing electrostatic interactions only by point charges can be augmented by the inclusion of atomic polarisabilities modelling charge flexibility. Two widely used models, Drude oscillators and induced point-dipoles, are compared in a systematic study using their respective implementations in CHARMM and AMBER. The question of necessity and importance of polarisable hydrogen atoms is raised and two implementations, in an implicit or explicit manner, are compared to the case of non-polarisable hydrogen atoms. For all these polarisability models, the strength of the respective atomic polarisabilities was incremented in steps of ten percent up to their full values. The influence of polarisability on the structure and dynamics of the ionic liquid EMIM(⊕)CF3SO, which is chosen as a test case, is studied thoroughly. Using appropriate model functions, the respective dynamical and structural data are fitted. Thus, a small set of parameters is deduced, which highlights the effect of polarisability. Generally, flexibility of the charge distribution leads to enhanced fluidity and less pronounced structure. As this usually occurs when adding a co-solvent to an ionic liquid, the inclusion of polarisability can be seen in much the same way in that it acts like an inner solvent.

The influence of urea on the conducting salt lithium bis-(trifluoromethanesulfonyl)-imide (LiTFSI) in terms of lithium ion coordination numbers and lithium ion transport properties is studied via atomistic molecular dynamics simulations. Our results indicate that the presence of urea favors the formation of a deep eutectic electrolyte with pronounced ion conductivities which can be explained by a competition between urea and TFSI in occupying the first coordination shell around lithium ions. All simulation findings verify that high urea concentrations lead to a significant increase of ionic diffusivities and an occurrence of relatively high lithium transference numbers in good agreement with experimental results. The outcomes of our study point at the possible application of deep eutectic electrolytes as ion conducting materials in lithium ion batteries.