Exploring asymmetry induced entropy in tetraalkylammonium-urea DES systems: what can be learned from inelastic neutron scattering?

In this work, inelastic neutron scattering (INS) spectroscopy is used to investigate the impact of entropic factors on the behaviour of deep eutectic solvents (DES). Periodic density functional theory calculations (DFT) provide a reliable assignment of the vibrational modes of pure compounds. This assignment guides the analysis of INS spectra of binary mixtures - with particular attention to methyl torsional modes. Deviations from ideality in the mixtures of tetraalkylammonium salts with urea are readily determined through a simplified thermodynamic approach. This study reports and discusses the relationship between the cation's asymmetry, the INS spectra of the eutectic mixture and its deviation from ideality. Contrary to the majority of systems studied so far, the deep eutectic system comprised of [N2,2,2,1]Cl and urea appears to owe its deviation from ideality to entropic rather than enthalpic factors.

The Role of the Anion in Imidazolium-Based Ionic Liquids for Fuel and Terpenes Processing.

The potentialities of methylimidazolium-based ionic liquids (ILs) as solvents were evaluated for some relevant separation problems-terpene fractionation and fuel processing-studying selectivities, capacities, and solvent performance indices. The activity coefficients at infinite dilution of the solute (1) in the IL (3), γ13∞, of 52 organic solutes were measured by inverse gas chromatography over a temperature range of 333.2-453.2 K. The selected ILs are 1-butyl-3-methylimidazolium hexafluorophosphate, [C4mim][PF6], and the equimolar mixture of [C4mim][PF6] and 1-butyl-3-methylimidazolium chloride, [C4mim]Cl. Generally, low polar solutes follow γ1,C4mimCl∞ > γ1,C4mimPF6+C4mimCl∞ > γ1,C4mimPF6∞ while the opposite behavior is observed for alcohols and water. For citrus essential oil deterpenation, the results suggest that cations with long alkyl chains, such as C12mim+, promote capacity, while selectivity depends on the solute polarity. Promising results were obtained for the separation of several model mixtures relevant to fuel industries using the equimolar mixture of [C4mim][PF6] and [C4mim]Cl. This work demonstrates the importance of tailoring the polarity of the solvents, suggesting the use of ILs with mixed anions as alternative solvents for the removal of aliphatic hydrocarbons and contaminants from fuels.

Liquefying Flavonoids with Terpenoids through Deep Eutectic Solvent Formation.

The formation of deep eutectic solvents (DES) is tied to negative deviations to ideality caused by the establishment of stronger interactions in the mixture than in the pure DES precursors. This work tested thymol and menthol as hydrogen bond donors when combined with different flavonoids. Negative deviations from ideality were observed upon mixing thymol with either flavone or flavanone, two parent flavonoids that only have hydrogen bond acceptor (HBA) groups, thus forming non-ionic DES (Type V). On the other hand, the menthol systems with the same compounds generally showed positive deviations from ideality. That was also the case with the mixtures containing the more complex hydroxylated flavonoid, hesperetin, which resulted in positive deviations when mixed with either thymol or menthol. COSMO-RS successfully predicted the behavior of the solid-liquid phase diagram of the studied systems, allowing for evaluation of the impact of the different contributions to the intermolecular interactions, and proving to be a good tool for the design of DES.

Differences on the impact of water on the deep eutectic solvents betaine/urea and choline/urea.

The differences on the impact of water on the intermolecular interactions present in the deep eutectic solvents betaine/urea and choline/urea are investigated in this work by measuring the solid-liquid phase diagrams of these mixtures with different amounts of added water. These data are analyzed in terms of ternary systems, rather than the usual pseudo-binary approach, and are used to calculate activity coefficients, which provide precious insight into how water affects the interactions of these systems. It is found that the addition of water greatly enhances the intermolecular interactions of betaine/urea near its eutectic composition, hinting at the formation of a 1:1:1 betaine/urea/water aggregate. On the other hand and contrary to what is commonly believed, water has an asymmetric impact on the interactions present in the choline/urea system. The addition of water to choline-rich mixtures leads to weaker interactions, whereas its addition to urea-rich mixtures leads to stronger interactions. This shows that the decrease in the melting temperature of choline/urea mixtures due to the presence of water does not necessarily mean that intermolecular interactions are strengthened. Finally, a minimum in the activity coefficient of urea in the choline/urea system with 2 wt. % of water was found, which coincides with several anomalies in the properties of this system previously reported in the literature.

The role of ionic vs. non-ionic excipients in APIs-based eutectic systems.

Aiming to contribute to drug pre-formulation, new eutectic mixtures were developed. Thymol, coumarin, or quaternary ammonium chlorides as excipients, were combined with the active pharmaceutical ingredients (APIs) acetylsalicylic acid, acetaminophen, ibuprofen, ketoprofen, or lidocaine. Their solid-liquid equilibrium (SLE) binary phase diagrams were measured to study eventual phase separation between the compounds, preventing manufacturing problems, and to study the molecular interactions between the APIs and ionic or non-ionic excipients. The Conductor-like Screening Model for Real Solvents (COSMO-RS) capability to predict the SLE of mixtures containing non-ionic excipients was further evaluated. COSMO-RS gives a good quantitative description of the experimental SLE being a tool with great potential in the screening of eutectic systems containing APIs and non-ionic excipients. While thymol presents strong interactions with the APIs, and consequently negative deviations to thermodynamic ideality, systems containing coumarin follow a quasi-ideal behavior. Regarding the ionic excipients, both choline chloride and the tetraalkylammonium chlorides are unable to establish relevant interactions with the APIs, and no significant negative deviations to ideality are observed. The liquefaction of the APIs here studied is favored by using non-ionic excipients, such as thymol, due to the strong interactions it can establish with the APIs.

Understanding the Formation of Deep Eutectic Solvents: Betaine as a Universal Hydrogen Bond Acceptor.

The mechanism of formation of betaine-based deep eutectic solvents (DES) is presented for the first time. Due to its polarity unbalance, it was found that betaine displays strong negative deviations from ideality when mixed with a variety of different organic substances. These results pave the way for a comprehensive design of novel deep eutectic solvents. A connection to biologically relevant systems was made using betaine (osmolyte) and urea (protein denaturant), showing that these two compounds formed a DES, the molecular interactions of which were greatly enhanced in the presence of water.

Liquefying Compounds by Forming Deep Eutectic Solvents: A Case Study for Organic Acids and Alcohols.

The criterion to distinguish a simple eutectic mixture from a deep eutectic solvent (DES) lies in the deviations to thermodynamic ideality presented by the components in the system. In this work, the current knowledge of the molecular interactions in types III and V DES is explored to liquefy a set of three fatty acids and three fatty alcohols, here used as model compounds for carboxyl and hydroxyl containing solid compounds. This work shows that thymol, a stronger than usual hydrogen bond donor, is able to form deep eutectic solvents of type V with the fatty alcohols studied. This is particularly interesting, since these DES formed are hydrophobic. Regarding type III DES, the results suggest that the prototypical DES hydrogen bond acceptor, cholinium chloride, is unable to induce negative deviations to ideality in the model molecules studied. By substituting choline with tetramethylammonium chloride, it is shown that the choline hydroxyl group is responsible for the difficulty in forming choline-based deep eutectic solvents and that its absence induces strong negative deviations to ideality in the alkylammonium side. Finally, it is demonstrated that tetrabutylammonium chloride acts as a chloride donning agent, causing significant negative deviations to ideality in both fatty acids and alcohols and leading to the formation of deep eutectic solvents of type III.

The Role of Charge Transfer in the Formation of Type I Deep Eutectic Solvent-Analogous Ionic Liquid Mixtures.

It was recently shown that tetramethylammonium chloride presented negative deviations to ideality when mixed with tetraethylammonium chloride or tetrapropylammonium chloride, leading to a strong decrease of the melting points of these salt mixtures, in a behavior akin to that observed in the formation of deep eutectic solvents. To better rationalize this unexpected melting point depression between two structurally similar compounds devoid of dominant hydrogen bonding capability, new solid-liquid equilibria data for tetramethylammonium-based systems were measured and analyzed in this work. Molecular dynamics was used to show that the strong negative deviations from ideality presented by these systems arise from a synergetic share of the chloride ions. A transfer of chloride ions seems to occur from the bigger cation in the mixture (which possesses a more disperse charge) to the smaller cation (tetramethylammonium), resembling the formation of metal-chloride complexes in type I deep eutectic solvents. This rearrangement of the charged species leads to an energetic stabilization of both components in the mixture, inducing the negative deviations to the ideality observed. The conclusions presented herein emphasize the often-neglected contribution of charge delocalization in deep eutectic solvents formation and its applicability toward the design of new ionic liquid mixtures.

What a difference a methyl group makes - probing choline-urea molecular interactions through urea structure modification.

There is a lack of fundamental knowledge on deep eutectic solvents, even for the most extensively studied mixtures, such as the mixture of cholinium chloride and urea, which prevents a judicious choice of components to prepare new solvents. The objective of this work is to study and understand the fundamental interactions between cholinium chloride and urea that lead to the experimentally observed melting temperature depression. To do so, the structure of urea was strategically and progressively modified, in order to block certain interaction centres, and the solid-liquid equilibrium data of each new binary system was experimentally measured. Using this approach, it was concluded that the most important interaction between cholinium chloride and urea occurs through hydrogen bonding between the chloride anion and the amine groups. Any blockage of these groups severely hampers the melting point depression effect. Raman spectroscopy and DFT calculations were utilized to study in more detail this hydrogen bonding and its nuances.

Phenolic hydrogen bond donors in the formation of non-ionic deep eutectic solvents: the quest for type V DES.

Mixtures of non-ionic compounds have been reported as DES but most are just ideal mixtures. In the thymol-menthol system, an abnormal strong interaction was identified stemming from the acidity difference of the phenolic and aliphatic hydroxyl groups. This type of interaction is found to be the key to prepare non-ionic DES, that may be classified as type V.

A methodology to parameterize SAFT-type equations of state for solid precursors of deep eutectic solvents: the example of cholinium chloride.

Given the recent boom of applications for deep eutectic solvents (DES), there is a need for robust and accurate thermodynamic models that are able to describe them. Recent works have used molecular-based equations of state, derived from the Statistical Associating Fluid Theory (SAFT), to model DES due to their ability to explicitly account for hydrogen bonding, which is thought to govern the formation of a DES. However, the application of these association models to DES is a non-trivial task, because pure fluid data for several DES precursors are not available to be used in the model parameterization. The alternative parameterization procedures currently employed have evident flaws including the use of oversimplified association schemes, lack of transferability, inability to provide fundamental solid-liquid equilibrium data, and an overall poor accuracy. This work highlights the disadvantages of the current approaches while providing a novel methodology for the development of coarse-grained models applicable to DES. By proposing a more realistic association scheme and regressing the model parameters from experimental data that can be easily measured for a representative DES, a new coarse-grained model for [Ch]Cl, the most used DES precursor, was developed for soft-SAFT. The good performance and versatility of the new model were then successfully demonstrated through the modelling of a wide variety of [Ch]Cl-based DES, providing accurate descriptions of densities, vapor-liquid equilibria and solid-liquid equilibria data, for both binary and ternary systems. Furthermore, the novel approach can easily be applied to other SAFT-type models and extended to other solid DES precursors such as urea.