A Computational and Spectroscopic Analysis of Solvate Ionic Liquids Containing Anions with Long and Short Perfluorinated Alkyl Chains.

Anion-driven, nanoscale polar-apolar structural organization is investigated in a solvate ionic liquid (SIL) setting by comparing sulfonate-based anions with long and short perfluorinated alkyl chains. Representative SILs are created from 1,2-bis(2-methoxyethoxy)ethane ("triglyme" or "G3"), lithium nonafluoro-1-butanesulfonate, and lithium trifluoromethanesulfonate. Molecular dynamics simulations, density functional theory computations, and vibrational spectroscopy provide insight into the overall liquid structure, cation-solvent interactions, and cation-anion association. Significant competition between G3 and anions for cation-binding sites characterizes the G3-LiC4F9SO3 mixtures. Only 50% of coordinating G3 molecules form tetradentate complexes with Li+ in [(G3)1Li][C4F9SO3]. Moreover, the SIL is characterized by extensive amounts of ion pairing. Based on these observations, [(G3)1Li][C4F9SO3] is classified as a "poor" SIL, similar to the analogous [(G3)1Li][CF3SO3] system. Even though the comparable basicity of the CF3SO3- and C4F9SO3- anions leads to similar SIL classifications, the hydrophobic fluorobutyl groups support extensive apolar domain formation. These apolar moieties permeate throughout [(G3)1Li][C4F9SO3] and persist even at relatively low dilution ratios of [(G3)10Li][C4F9SO3]. By way of comparison, the CF3 group is far too short to sustain polar-apolar segregation. This demonstrates how chemically modifying the anions to include hydrophobic groups can impart unique nanoscale organization to a SIL. Moreover, tuning these nano-segregated fluorinated domains could, in principle, control the presence of dimensionally ordered states in these mixtures without changing the coordination of the lithium ions.

Unraveling the Morphology of [CnC1Im]Cl Ionic Liquids Combining Cluster and Aggregation Analyses.

A characteristic feature of ionic liquids is their nanosegregation, resulting in the formation of polar and nonpolar domains. The influence of increasing the alkyl side chain on the morphology of ionic liquids has been the subject of many studies. Typically, the polar network (charged part of the cation and anion) constitutes a continuous subphase that partially breaks to allow the formation of a nonpolar domain with the increase of the alkyl chain. As the nonpolar network expands, the number of tails per aggregate increases until the ionic liquid percolates. In this work, we demonstrate how the complementary software packages TRAVIS and AGGREGATES can be employed in conjunction to gain insights into the size and morphology of the [CnC1Im]Cl family, with n ∈ {2, 4, 6, 8, 10, 12}. The combination of the two approaches rounds off the picture of the intricate arrangement and structural features of the alkyl chains.

Molecular Interactions between Ionic Liquid Lubricants and Silica Surfaces: An MD Simulation Study.

The unique physicochemical properties of ionic liquids (ILs) attracted interest in their application as lubricants of micro/nano-electromechanical systems. This work evaluates the feasibility of using the protic ionic liquids [4-picH][HSO4], [4-picH][CH3SO3], [MIMH][HSO4], and [MIMH][CH3SO3] and the aprotic ILs [C6mim][HSO4] and [C6mim][CH3SO3] as additives to model lubricant poly(ethylene glycol) (PEG200) to lubricate silicon surfaces. Additives based on the cation [4-picH]+ exhibited the best tribological performance, with the optimal value for 2% [4-picH][HSO4] in PEG200 (w/w). Molecular dynamics (MD) simulations of the first stages of adsorption of the ILs at the glass surface were performed to portray the molecular behavior of the ILs added to PEG200 and their interaction with the silica substrate. For the pure ILs at the solid substrates, the MD results indicated that weak specific interactions of the cation with the glass interface are lost to accommodate the larger anion in the first contact layer. For the PEG200 + 2% [4-picH][HSO4] system, the formation of a more compact protective film adsorbed at the glass surface is revealed by a larger trans population of the dihedral angle -O(R)-C-C-O(R)- in PEG200, in comparison to the same distribution for the pure model lubricant. Our findings suggest that the enhanced lubrication performance of PEG200 with [4-picH][HSO4] arises from synergistic interactions between the protic IL and PEG200 at the adsorbed layer.

Understanding the Liquid Structure in Mixtures of Ionic Liquids with Semiperfluoroalkyl or Alkyl Chains.

By mixing ionic liquids (ILs), it is possible to fine-tune their bulk and interfacial structure. This alters their physical properties and solvation behavior and is a simple way to prepare a collection of ILs whose properties can be tuned to optimize a specific application. In this study, mixtures of perfluorinated and alkylated ILs have been prepared, and links between composition, properties, and nanostructure have been investigated. These different classes of ILs vary substantially in the flexibility and polarizability of their chains. Thus, a range of useful structural and physical property variations are accessible through mixing that will expand the library of IL mixtures available in an area that to this point has received relatively little attention. In the experiments presented herein, the physical properties and bulk structure of mixtures of 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide [C8MIM][Tf2N] and 1-(1H,1H,2H,2H-perfluorooctyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [C8MIM-F13][Tf2N] have been prepared. The bulk liquid structure was investigated using a combination of small-angle X-ray and neutron scattering (SAXS and SANS, respectively) experiments in combination with atomistic molecular dynamics simulations and the measurement of density and viscosity. We observed that the addition of [C8MIM-F13][Tf2N] to [C8MIM][Tf2N] causes changes in the nanostructure of the IL mixtures that are dependent on composition so that variation in the characteristic short-range correlations is observed as a function of composition. Thus, while the length scales associated with the apolar regions (polar non-polar peak─PNPP) increase with the proportion of [C8MIM-F13][Tf2N] in the mixtures, perhaps surprisingly given the greater volume of the fluorocarbon chains, the length scale of the charge-ordering peak decreases. Interestingly, consideration of the contact peak shows that its origins are both in the direct anion···cation contact length scale and the nature (and hence volume) of the chains appended to the imidazolium cation.

The Nanostructure of Alkyl-Sulfonate Ionic Liquids: Two 1-Alkyl-3-methylimidazolium Alkyl-Sulfonate Homologous Series.

The functionalization of polymers with sulfonate groups has many important uses, ranging from biomedical applications to detergency properties used in oil-recovery processes. In this work, several ionic liquids (ILs) combining 1-alkyl-3-methylimidazolium cations [CnC1im]+ (4 ≤ n ≤ 8) with alkyl-sulfonate anions [CmSO3]- (4 ≤ m ≤ 8) have been studied using molecular dynamics simulations, totalizing nine ionic liquids belonging to two homologous series. The radial distribution functions, structure factors, aggregation analyses, and spatial distribution functions reveal that the increase in aliphatic chain length induces no significant change in the structure of the polar network of the ILs. However, for imidazolium cations and sulfonate anions with shorter alkyl chains, the nonpolar organization is conditioned by the forces acting on the polar domains, namely, electrostatic interactions and hydrogen bonding.

Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer's Disease.

Alzheimer's Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aß plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested ß-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility.

Ionic Liquids and Water: Hydrophobicity vs. Hydrophilicity.

Many chemical processes rely extensively on organic solvents posing safety and environmental concerns. For a successful transfer of some of those chemical processes and reactions to aqueous media, agents acting as solubilizers, or phase-modifiers, are of central importance. In the present work, the structure of aqueous solutions of several ionic liquid systems capable of forming multiple solubilizing environments were modeled by molecular dynamics simulations. The effect of small aliphatic chains on solutions of hydrophobic 1-alkyl-3-methylimidazolium bis(trifluoromethyl)sulfonylimide ionic liquids (with alkyl = propyl [C3C1im][NTf2], butyl [C4C1im][NTf2] and isobutyl [iC4C1im][NTf2]) are covered first. Next, we focus on the interactions of sulphonate- and carboxylate-based anions with different hydrogenated and perfluorinated alkyl side chains in solutions of [C2C1im][CnF2n+1SO3], [C2C1im][CnH2n+1SO3], [C2C1im][CF3CO2] and [C2C1im][CH3CO2] (n = 1, 4, 8). The last system considered is an ionic liquid completely miscible with water that combines the cation N-methyl-N,N,N-tris(2-hydroxyethyl)ammonium [N1 2OH 2OH 2OH]+, with high hydrogen-bonding capability, and the hydrophobic anion [NTf2]-. The interplay between short- and long-range interactions, clustering of alkyl and perfluoroalkyl tails, and hydrogen bonding enables a wealth of possibilities in tailoring an ionic liquid solution according to the needs.

The Solubility of Gases in Ionic Liquids: A Chemoinformatic Predictive and Interpretable Approach.

This work comprises the study of solubilities of gases in ionic liquids (ILs) using a chemoinformatic approach. It is based on the codification, of the atomic inter-component interactions, cation/gas and anion/gas, which are used to obtain a pattern of activation in a Kohonen Neural Network (MOLMAP descriptors). A robust predictive model has been obtained with the Random Forest algorithm and used the maximum proximity as a confidence measure of a given chemical system compared to the training set. The encoding method has been validated with molecular dynamics. This encoding approach is a valuable estimator of attractive/repulsive interactions of a generical chemical system IL+gas. This method has been used as a fast/visual form of identification of the reasons behind the differences observed between the solubility of CO2 and O2 in 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM PF6 ) at identical temperature and pressure (TP) conditions, The effect of variable cation and anion effect has been evaluated.

Tailoring amphotericin B as an ionic liquid: an upfront strategy to potentiate the biological activity of antifungal drugs.

Aspergillus species are the primary cause of invasive aspergillosis, which afflicts hundreds of thousands of patients yearly, with high mortality rates. Amphotericin B is considered the gold standard in antifungal drug therapy, due to its broad-spectrum activity and rarely reported resistance. However, low solubility and permeability, as well as considerable toxicity, challenge its administration. Lipid formulations of amphotericin B have been used to promote its slow release and diminish toxicity, but these are expensive and adverse health effects of their prolonged use have been reported. In the past decades, great interest emerged on converting biologically active molecules into an ionic liquid form to overcome limitations such as low solubility or polymorphisms. In this study, we evaluated the biological activity of novel ionic liquid formulations where the cholinium, cetylpyridinium or trihexyltetradecylphosphonium cations were combined with an anionic form of amphotericin B. We observed that two formulations increased the antifungal activity of the drug, while maintaining its mode of action. Molecular dynamics simulations showed that higher biological activity was due to increased interaction of the ionic liquid with the fungal membrane ergosterol compared with amphotericin B alone. Increased cytotoxicity could also be observed, probably due to greater interaction of the cation with cholesterol, the main sterol in animal cells. Importantly, one formulation also displayed antibacterial activity (dual functionality), likely preserved from the cation. Collectively, the data set ground for the guided development of ionic liquid formulations that could improve the administration, efficacy and safety of antifungal drugs or even the exploitation of their dual functionality.

Vapor Pressure Assessment of Sulfolane-Based Eutectic Solvents: Experimental, PC-SAFT, and Molecular Dynamics.

Since their discovery, deep eutectic solvents (DES) have been explored in multiple applications. However, the complete physicochemical characterization is still nonexistent for many of the proposed and used DES. In particular, vapor pressure, which is a crucial property for the application of DES as solvents, is very rarely available. In this work, the measurement of the total and partial pressures of two sulfolane-based DES, tetrabutylammonium bromide:sulfolane and tetrabutylphosphonium bromide:sulfolane, in several proportions, from 40 to 100 °C and atmospheric pressure, was performed using headspace gas chromatography mass spectrometry, HS-GC-MS. A large decrease on the total pressure was recorded which, together with the finding that total pressures showed negative deviations from Raoult's law, is indicative of the favorable, strong interactions between the two components within the DES. Additionally, the study of vapor pressure change with DES molar composition was carried out, and surprisingly, the existence of inflection points in the pressure curve was observed. Experimental results were modeled using the PC-SAFT equation of state, and in addition, MD simulations were performed to provide a molecular understanding of the pressure data. Considering the different results and insights obtained from the used strategies, it can be concluded that both DES systems have especially strong interactions between salt and sulfolane, at high sulfolane content, due to the different structural rearrangement of the liquid state.

Photon Upconversion in TTA-Inducing Ionic Liquids: Pinpointing the Role of IL Nanostructured Media Using MD Simulations.

The use of task-specific chromophoric ionic liquids as energy transfer media in triplet-triplet annihilation photon upconversion (TTA-UC) processes has produced several examples of systems with signifficantly enhanced performances. In this work, we use molecular dynamics simulations to probe the relation between the nanostructure of chromophoric ionic liquids and their ability to achieve high TTA-UC quantum yields. The existing atomistic and systematic force fields commonly used to model different ionic liquids are extended to include substituted anthracene moieties, thus allowing the modeling of several chromophoric ionic liquids. The simulation results show that the polar network of the ionic liquids can orient the anthracene moieties within the nonpolar domains preventing direct contacts between them but allowing orientations at the optimal distance for triplet energy migration.

Solvate ionic liquids based on lithium bis(trifluoromethanesulfonyl)imide-glyme systems: coordination in MD simulations with scaled charges.

Equimolar mixtures of lithium bis(trifluoromethanesulfonyl)imide (Li[NTf2]) with triglyme or tetraglyme (small oligoethers) are regarded as a new class of ionic liquids, the so-called solvate ionic liquids. In these mixtures, the glyme molecules wrap around the lithium ions forming crown-ether like [Li(glyme)1]+ complex cations. New molecular dynamics (MD) simulations suggest that the lithium-glyme coordination is stronger than that predicted in a former MD study [K. Shimizu, et al., Phys. Chem. Chem. Phys., 2015, 17, 22321-22335], whereas lithium-NTf2 connections are weaker. The differences between the present and the previous study arise from different starting conditions. Both studies employed charges scaled by a factor of 0.8. As shown by the comparison of MD simulations with and without reduced charges to experiments, charge scaling is necessary in order to obtain data close to experimental results.

Halogen and Hydrogen Bonding Interplay in the Crystal Packing of Halometallocenes.

This paper focuses in the influence of halogen atoms in the design and structural control of the crystal packing of Group VIII halogenated metallocenes. The study is based on the present knowledge on new types of intermolecular contacts such as halogen (X⋯X, C-X⋯H, C-X⋯π), π⋯π, and C-H⋯π interactions. The presence of novel C-H⋯M interactions is also discussed. Crystal packings are analysed after database search on this family of compounds. Results are supported by ab initio calculations on electrostatic charge distributions; Hirshfeld analysis is also used to predict the types of contacts to be expected in the molecules. Special attention is given to the competition among hydrogen and halogen interactions, mainly its influence on the nature and geometric orientations of the different supramolecular motifs. Supramolecular arrangements of halogenated metallocenes and Group IV di-halogenated bent metallocenes are also compared and discussed. Analysis supports halogen bonds as the predominant interactions in defining the crystal packing of bromine and iodine 1,1'-halometallocenes.

Structure and dynamics of mica-confined films of [C10C1Pyrr][NTf2] ionic liquid.

The structure of the ionic liquid 1-decyl-1-methylpyrrolidinium bis[(trifluoromethane)sulfonyl]imide, [C10C1Pyrr][NTf2], has been probed using Molecular Dynamics (MD) simulations. The simulations endeavour to model the behaviour of the ionic liquid in bulk isotropic conditions and also at interfaces and in confinement. The MD results have been confronted and validated with scattering and surface force experiments reported in the literature. The calculated structure factors, distribution functions, and density profiles were able to provide molecular and mechanistic insights into the properties of these long chain ionic liquids under different conditions, in particular those that lead to the formation of multi-layered ionic liquid films in confinement. Other properties inaccessible to experiment such as in-plane structures and relaxation rates within the films have also been analysed. Overall the work contributes structural and dynamic information relevant to many applications of ionic liquids with long alkyl chains, ranging from nanoparticle synthesis to lubrication.

Molecular dynamics studies on the structure and interactions of ionic liquids containing amino-acid anions.

Several molecular dynamics (MD) simulations have been performed in order to obtain structural information on ionic liquids (ILs) based on amino-acid anions. Six hydrophilic ILs containing cholinium or imidazolium cations combined with alaninate, glycinate or lysinate anions were modelled using the all-atom CL&P and OPLS-AA force fields. Both pure ILs and their aqueous solutions have been studied. The MD data have allowed us to analyse structure factors, S(q), and pair radial distributions functions, g(r), as well as aggregation patterns and specific interactions. The results have shown us that in neat amino-acid-based ILs the anions interact mainly through their carboxylate moiety with the charged centres of the cations. Both the lack of heavy atoms and the small size of the interacting centre in the anion contribute to the absence of a charge ordering peak in the structure factor functions of the corresponding ILs. In turn, their aqueous solutions reveal the existence of small ionic aggregates. The size distribution of these aggregates is strongly dependent on the solution's concentration. This fact points to the possibility of using amino-acid-based ILs as agents to promote hydrotrope effects, significant for the solubilisation and stabilization of organic molecules and macromolecules in aqueous solution.

Design of task-specific fluorinated ionic liquids: nanosegregation versus hydrogen-bonding ability in aqueous solutions.

We demonstrate that fluorinated ionic liquids reduce the impact of the addition of water upon the ionic liquid's H-bond acceptance ability. This is a key factor to obtain functionalized materials to be used e.g. in the dissolution of biomolecules, extraction processes or material engineering.

Probing the Surface Tension of Ionic Liquids Using the Langmuir Principle.

At 298 K, the surface tension of ionic liquids (ILs) of the 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide series, [C nC1Im][NTf2], ranges from around 35 mN·m-1 for [C2C1Im][NTf2] to just below 30 mN·m-1 for [C12C1Im][NTf2]. However, the decrease rate along the series is not constant: a large decrease from [C2C1Im][NTf2] to [C8C1Im][NTf2] is followed by almost constant values from [C8C1Im][NTf2] to [C12C1Im][NTf2]. Such behavior is hard to interpret from a molecular point of view without suitable information about the free-surface structure of the different ILs. In this work, we have successfully used the Langmuir principle in combination with structural data obtained from angle-resolved X-ray photoelectron spectroscopy experiments and molecular dynamics simulations, to predict the correct surface tension trend along the IL series. The concepts unveiled for this particular homologous IL family can be easily extended to other systems.

ILs through the looking glass: electrostatics and structure probed using charge-inverted ionic liquid pairs.

Ionic liquids combining potassium cations with 1-alkyl-3-methylcyclopentadienyl anions, K[CnC1Cp] (n = 4, 6) have been synthesized. Differential scanning calorimetry measurements have shown that K[C4C1Cp] and K[C6C1Cp] melt without decomposition at around 90 °C. These two ionic liquids are the charge-inverted counterparts of [C4C1Im]Cl and [C6C1Im]Cl, two common ionic liquids. The concept of charge-inverted ionic pairs is used to explore the nature of the interactions and structure in different ionic compounds, from simple alkali halide salts to ionic liquids based on complex molecular ions. Different sets of experimental data, empirical correlations and molecular dynamics simulations are used to that effect.

Exploring the bulk-phase structure of ionic liquid mixtures using small-angle neutron scattering.

Small-angle neutron scattering experiments, supported by molecular dynamics simulations, have been performed on a range of compositions of the [C2mim]1-x[C12mim]x[Tf2N] ionic liquid mixture system. Isotopic contrast variation, through selective deuteration of both cations, has been used to assist in fitting the data to different scattering models. These data, and subsequent fitting, show that the structure of the ionic liquid mixtures changes substantially as a function of composition. Mixtures where x < 0.32 are dominated by aggregates of amphiphilic [C12mim]+ ions in the relatively polar [C2mim][Tf2N] solvent. Compositions where x > 0.32 can be described as bicontinuous, containing networks of both polar and non-polar domains, where the C12 chains of the [C12mim]+ ions percolate through the system to form a continuous non-polar sub-phase. Temperature-dependent scattering experiments suggest that there is relatively little change in bulk structure in these liquids between 20 and 60 °C. The presence of water, however, does influence some aspects of the liquid structure in a composition that is rich in [C2mim][Tf2N] (where x = 0.24).