Lyotropic liquid crystal phases of monoolein in protic ionic liquids.

Monoolein-based liquid crystal phases are established media that are researched for various biological applications, including drug delivery. While water is the most common solvent for self-assembly, some ionic liquids (ILs) can support lipidic self-assembly. However, currently, there is limited knowledge of IL-lipid phase behavior in ILs. In this study, the lyotropic liquid crystal phase behavior of monoolein was investigated in six protic ILs known to support amphiphile self-assembly, namely ethylammonium nitrate, ethanolammonium nitrate, ethylammonium formate, ethanolammonium formate, ethylammonium acetate, and ethanolammonium acetate. These ILs were selected to identify specific ion effects on monoolein self-assembly, specifically increasing the alkyl chain length of the cation or anion, the presence of a hydroxyl group in the cation, and varying the anion. The lyotropic liquid crystal phases with 20-80 wt. % of monoolein were characterized over a temperature range from 25 to 65 °C using synchrotron small angle x-ray scattering and cross-polarized optical microscopy. These results were used to construct partial phase diagrams of monoolein in each of the six protic ILs, with inverse hexagonal, bicontinuous cubic, and lamellar phases observed. Protic ILs containing the ethylammonium cation led to monoolein forming lamellar and bicontinuous cubic phases, while those containing the ethanolammonium cation formed inverse hexagonal and bicontinuous cubic phases. Protic ILs containing formate and acetate anions favored bicontinuous cubic phases across a broader range of protic IL concentrations than those containing the nitrate anion.

Automation of liquid crystal phase analysis for SAXS, including the rapid production of novel phase diagrams for SDS-water-PIL systems.

Lyotropic liquid crystal phases (LCPs) are widely studied for diverse applications, including protein crystallization and drug delivery. The structure and properties of LCPs vary widely depending on the composition, concentration, temperature, pH, and pressure. High-throughput structural characterization approaches, such as small-angle x-ray scattering (SAXS), are important to cover meaningfully large compositional spaces. However, high-throughput LCP phase analysis for SAXS data is currently lacking, particularly for patterns of multiphase mixtures. In this paper, we develop semi-automated software for high throughput LCP phase identification from SAXS data. We validate the accuracy and time-savings of this software on a total of 668 SAXS patterns for the LCPs of the amphiphile hexadecyltrimethylammonium bromide (CTAB) in 53 acidic or basic ionic liquid derived solvents, within a temperature range of 25-75 °C. The solvents were derived from stoichiometric ethylammonium nitrate (EAN) or ethanolammonium nitrate (EtAN) by adding water to vary the ionicity, and adding precursor ions of ethylamine, ethanolamine, and nitric acid to vary the pH. The thermal stability ranges and lattice parameters for CTAB-based LCPs obtained from the semi-automated analysis showed equivalent accuracy to manual analysis, the results of which were previously published. A time comparison of 40 CTAB systems demonstrated that the automated phase identification procedure was more than 20 times faster than manual analysis. Moreover, the high throughput identification procedure was also applied to 300 unpublished scattering patterns of sodium dodecyl-sulfate in the same EAN and EtAN based solvents in this study, to construct phase diagrams that exhibit phase transitions from micellar, to hexagonal, cubic, and lamellar LCPs. The accuracy and significantly low analysis time of the high throughput identification procedure validates a new, rapid, unrestricted analytical method for the determination of LCPs.

Observations of phase changes in monoolein during high viscous injection.

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations.

Electrochemical Stability of Zinc and Copper Surfaces in Protic Ionic Liquids.

Ionic liquids are versatile solvents that can be tailored through modification of the cation and anion species. Relatively little is known about the corrosive properties of protic ionic liquids. In this study, we have explored the corrosion of both zinc and copper within a series of protic ionic liquids consisting of alkylammonium or alkanolammonium cations paired with nitrate or carboxylate anions along with three aprotic imidazolium ionic liquids for comparison. Electrochemical studies revealed that the presence of either carboxylate anions or alkanolammonium cations tend to induce a cathodic shift in the corrosion potential. The effect in copper was similar in magnitude for both cations and anions, while the anion effect was slightly more pronounced than that of the cation in the case of zinc. For copper, the presence of carboxylate anions or alkanolammonium cations led to a notable decrease in corrosion current, whereas an increase was typically observed for zinc. The ionic liquid-metal surface interactions were further explored for select protic ionic liquids on copper using X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) to characterize the interface. From these studies, the oxide species formed on the surface were identified, and copper speciation at the surface linked to ionic liquid and potential dependent surface passivation. Density functional theory and ab initio molecular dynamics simulations revealed that the ethanolammonium cation was more strongly bound to the copper surface than the ethylammonium counterpart. In addition, the nitrate anion was more tightly bound than the formate anion. These likely lead to competing effects on the process of corrosion: the tightly bound cations act as a source of passivation, whereas the tightly bound anions facilitate the electrodissolution of the copper.

Machine learning investigation of viscosity and ionic conductivity of protic ionic liquids in water mixtures.

Ionic liquids (ILs) are well classified as designer solvents based on the ease of tailoring their properties through modifying the chemical structure of the cation and anion. However, while many structure-property relationships have been developed, these generally only identify the most dominant trends. Here, we have used machine learning on existing experimental data to construct robust models to produce meaningful predictions across a broad range of cation and anion chemical structures. Specifically, we used previously collated experimental data for the viscosity and conductivity of protic ILs [T. L. Greaves and C. J. Drummond, Chem. Rev. 115, 11379-11448 (2015)] as the inputs for multiple linear regression and neural network models. These were then used to predict the properties of all 1827 possible cation-anion combinations (excluding the input combinations). These models included the effect of water content of up to 5 wt. %. A selection of ten new protic ILs was then prepared, which validated the usefulness of the models. Overall, this work shows that relatively sparse data can be used productively to predict physicochemical properties of vast arrays of ILs.

Protic Ionic Liquid Cation Alkyl Chain Length Effect on Lysozyme Structure.

Solvents that stabilize protein structures can improve and expand their biochemical applications, particularly with the growing interest in biocatalytic-based processes. Aiming to select novel solvents for protein stabilization, we explored the effect of alkylammonium nitrate protic ionic liquids (PILs)-water mixtures with increasing cation alkyl chain length on lysozyme conformational stability. Four PILs were studied, that is, ethylammonium nitrate (EAN), butylammonium nitrate (BAN), hexylammonium nitrate (HAN), and octylammonium nitrate (OAN). The surface tension, viscosity, and density of PIL-water mixtures at low to high concentrations were firstly determined, which showed that an increasing cation alkyl chain length caused a decrease in the surface tension and density as well as an increase in viscosity for all PIL solutions. Small-angle X-ray scattering (SAXS) was used to investigate the liquid nanostructure of the PIL solutions, as well as the overall size, conformational flexibility and changes to lysozyme structure. The concentrated PILs with longer alkyl chain lengths, i.e., over 10 mol% butyl-, 5 mol% hexyl- and 1 mol% octylammonium cations, possessed liquid nanostructures. This detrimentally interfered with solvent subtraction, and the more structured PIL solutions prevented quantitative SAXS analysis of lysozyme structure. The radius of gyration (Rg) of lysozyme in the less structured aqueous PIL solutions showed little change with up to 10 mol% of PIL. Kratky plots, SREFLEX models, and FTIR data showed that the protein conformation was maintained at a low PIL concentration of 1 mol% and lower when compared with the buffer solution. However, 50 mol% EAN and 5 mol% HAN significantly increased the Rg of lysozyme, indicating unfolding and aggregation of lysozyme. The hydrophobic interaction and liquid nanostructure resulting from the increased cation alkyl chain length in HAN likely becomes critical. The impact of HAN and OAN, particularly at high concentrations, on lysozyme structure was further revealed by FTIR. This work highlights the negative effect of a long alkyl chain length and high concentration of PILs on lysozyme structural stability.

Ultrafast dynamics and scattering of protic ionic liquids induced by XFEL pulses.

X-rays are routinely used for structural studies through scattering, and femtosecond X-ray lasers can probe ultrafast dynamics. We aim to capture the femtosecond dynamics of liquid samples using simulations and deconstruct the interplay of ionization and atomic motion within the X-ray laser pulse. This deconstruction is resolution dependent, as ionization influences the low momentum transfers through changes in scattering form factors, while atomic motion has a greater effect at high momentum transfers through loss of coherence. Our methodology uses a combination of classical molecular dynamics and plasma simulation on a protic ionic liquid to quantify the contributions to the scattering signal and how these evolve with time during the X-ray laser pulse. Our method is relevant for studies of organic liquids, biomolecules in solution or any low-Z materials at liquid densities that quickly turn into a plasma while probed with X-rays.

Systematic Comparison of the Structural and Dynamic Properties of Commonly Used Water Models for Molecular Dynamics Simulations.

Water is a unique solvent that is ubiquitous in biology and present in a variety of solutions, mixtures, and materials settings. It therefore forms the basis for all molecular dynamics simulations of biological phenomena, as well as for many chemical, industrial, and materials investigations. Over the years, many water models have been developed, and it remains a challenge to find a single water model that accurately reproduces all experimental properties of water simultaneously. Here, we report a comprehensive comparison of structural and dynamic properties of 30 commonly used 3-point, 4-point, 5-point, and polarizable water models simulated using consistent settings and analysis methods. For the properties of density, coordination number, surface tension, dielectric constant, self-diffusion coefficient, and solvation free energy of methane, models published within the past two decades consistently show better agreement with experimental values compared to models published earlier, albeit with some notable exceptions. However, no single model reproduced all experimental values exactly, highlighting the need to carefully choose a water model for a particular study, depending on the phenomena of interest. Finally, machine learning algorithms quantified the relationship between the water model force field parameters and the resulting bulk properties, providing insight into the parameter-property relationship and illustrating the challenges of developing a water model that can accurately reproduce all properties of water simultaneously.

Machine learning approaches to understand and predict rate constants for organic processes in mixtures containing ionic liquids.

The ability to tailor the constituent ions in ionic liquids (ILs) is highly advantageous as it provides access to solvents with a range of physicochemical properties. However, this benefit also leads to large compositional spaces that need to be explored to optimise systems, often involving time consuming experimental work. The use of machine learning methods is an effective way to gain insight based on existing data, to develop structure-property relationships and to allow the prediction of ionic liquid properties. Here we have applied machine learning models to experimentally determined rate constants of a representative organic process (the reaction of pyridine with benzyl bromide) in IL-acetonitrile mixtures. Multiple linear regression (MLREM) and artificial neural networks (BRANNLP) were both able to model the data well. The MLREM model was able to identify the structural features on the cations and anions that had the greatest effect on the rate constant. Secondly, predictive MLREM and BRANNLP models were developed from the full initial set of rate constant data. From these models, a large number of predictions (>9000) of rate constant were made for mixtures of different ionic liquids, at different proportions of ionic liquid and molecular solvent, at different temperatures. A selection of these predictions were tested experimentally, including through the preparation of novel ionic liquids, with overall good agreement between the predicted and experimental data. This study highlights the benefits of using machine learning methods on kinetic data in ionic liquid mixtures to enable the development of rigorous structure-property relationships across multiple variables simultaneously, and to predict properties of new ILs and experimental conditions.

Lyotropic liquid crystal phase behavior of a cationic amphiphile in aqueous and non-stoichiometric protic ionic liquid mixtures.

Protic ionic liquids (PILs) are the largest and most tailorable known class of non-aqueous solvents which possess the ability to support amphiphile self-assembly. However, little is known about the effect of solvent additives on this ability. In this study, the lyotropic liquid crystal phase (LLCP) behavior of the cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated in the model PILs of ethylammonium nitrate (EAN) and ethanolammonium nitrate (EtAN), and derived multi-component solvent systems containing them to determine phase formation and diversity with changing solvent composition. The solvent systems were composed of water, nitric acid and ethylamine (or ethanolamine), with 26 unique compositions for each PIL covering the apparent pH and ionicity ranges of 0-13.5 and 0-11 M, respectively. The LLCPs were studied using cross polarized optical microscopy (CPOM) and small and wide-angle X-ray scattering (SAXS/WAXS). Partial phase diagrams were constructed for CTAB concentrations of 50 wt% and 70 wt% in the temperature range of 25 °C to 75 °C to characterise the effect of surfactant concentration and temperature on the LLCPs in each solvent environment. Normal micellar (L1), hexagonal (H1) and bicontinuous cubic (V1) phases were identified at both surfactant concentrations, and from temperatures as low as 35 °C, with large variations dependent on the solvent composition. The thermal stability and diversity of phases were greater and broader in solvent compositions with excess precursor amines present compared to those in the neat PILs. In acid-rich solvent combinations, the same phase diversity was found, though with reduced onset temperatures of phase formation; however, some structural changes were observed which were attributed to oxidation/decomposition of CTAB in a nitric acid environment. This study showed that the ability of PIL solutions to support amphiphile self-assembly can readily be tuned, and that the ability of PILs to promote amphiphile self-assembly is robust, even with other solvent species present.

Solvation properties of protic ionic liquid-molecular solvent mixtures.

Ionic liquids (ILs) are increasingly receiving interest for a wide range of applications. However, for many applications their cost and/or viscosity can be too high. This can be addressed by using protic ionic liquids as cheaper alternatives, and through mixing with molecular solvents. However, mixing ILs with a molecular solvent adds another dimension to the compositional space, as well as increasing the complexity of solvent-solute interactions. In this study, we have investigated the solvation properties of binary mixtures of PILs with molecular solvents. The selected binary solvent systems are the PILs ethylammonium nitrate (EAN) and propylammonium nitrate (PAN) combined with either water, methanol, acetonitrile or DMSO. In addition, water is combined with the other molecular solvents for comparison. The mole fractions of the secondary solvents were 0, 0.25, 0.5, 0.75, 0.9 and 1 for all combinations, which resulted in a total of 66 solvent mixtures. The solvation properties in each of these mixtures were determined from spectroscopic measurements of 4 well-known solvatochromic probe molecules as solutes. The solvation properties were comparatively investigated, and interpreted, in terms of the specific and non-specific interactions between PIL-solvent, PIL-solute and solvent-solute. All 66 solvent mixtures were also analysed using FTIR with no probe molecules present. In addition, through molecular dynamics simulations, the dye-solvent interactions were simulated for two of the dye molecules in water-EAN binary systems, and the radial distribution functions for the key interactions were obtained. The results showed that the solvation parameters of the binary mixtures deviated considerably from the ideal solvation behaviour. In many cases, bulk compositions and the estimated excess compositions in the solvation shells of the probes were different, suggesting preferential solvation, the extent of which is solute dependent. Our results clearly show that using PILs in a mixture with molecular solvents can strongly enhance the solvation capability.

Physicochemical characterisation of novel tetrabutylammonium aryltrifluoroborate ionic liquids.

While there have been many studies on the physicochemical characterisation of ILs, little work has previously been reported on the properties unique to the trifluoroborate anion. Here we have characterised the thermal properties, viscosity, liquid nanostructure and intramolecular interactions of 15 novel aryltrifluoroborate ILs. These ILs all contained a tetrabutylammonium cation paired with either meta- or para-substituted aryltrifluoroborate anions, or di-anionic substituted aryltrifluroborate anions. It was found that of the 15 samples analysed, 4 would technically be considered molten salts as they have melting points greater than 100 °C. Overall the structure-property relationship trends of these samples are similar to those previously reported for alkyl and perfluoroalkyltrifluoroborate ILs which contained K+ or Cs+ cations, with the big difference being the ILs in this study having considerably lower melting points.

Structural investigations of molecular solutes within nanostructured ionic liquids.

Ionic liquids (ILs) containing sufficiently long alkyl chains form amphiphilic nanostructures with well-defined polar and non-polar domains. Here we have explored the robustness of these amphiphilic nanostructures to added solutes and gained insight into how the nature of the solute and IL ions affect the partitioning of these solutes within the nanostructured domains of ILs. To achieve this, small angle X-ray scattering (SAXS) investigations were performed and discussed for mixtures of 9 different molecular compounds with 6 different ILs containing imidazolium cations. The amphiphilic nanostructure of ILs persisted to high solute concentrations, over 50 mol% of added solute for most 1-butyl-3-methylimidazolium ILs and above 80 mol% for most 1-decyl-3-methylimidazolium ILs. Solute partitioning within these domains was found to be controlled by the inherent polarity and size of the solute, as well as specific interactions between the solute and IL ions, with SAXS results corroborated with IR spectroscopy and molecular dynamics simulations. Molecular dynamics simulations also revealed the ability to induce π+-π+ stacking between imidazolium cations through the use of these added molecular compounds. Collectively, these results provide scope for the selection of IL ions to rationally influence and control the partitioning behaviour of given solutes within the amphiphilic nanostructure of ILs.

Solvation properties of protic ionic liquids and molecular solvents.

Ionic liquids (ILs) are highly tailorable solvents with many potential applications. Knowledge about their solvation properties is highly beneficial in the utilization of ILs for specific tasks, though for many ILs this is currently unknown. In this study, we have investigated the solvation properties of 12 protic ionic liquids (PILs) and 9 molecular solvents based on the Kamlet-Abboud-Taft' (KAT) multi-parameter solvation scales. The KAT parameters, which are dipolarity/polarizability (π*), HBD acidity (α), HBA basicity (ß), and the electronic transition energy (ET) were first obtained for the molecular solvents with an extensive set of 11 solvatochromic probe dye molecules. Based on these results the dyes which exhibited the highest sensitivities to polarity changes, and had the greatest chemical stability, were used to determine the KAT parameters of 12 PILs which contained alkyl-, dialkyl-, alkanol-, or dialkanolammonium cations paired with nitrate, formate or acetate anions. Solvation parameters were also obtained for the PILs using the three fluorescent probes pyrene, Coumarin 153 and Nile red for comparison. The PILs containing nitrate anions showed the greatest polarity, polarizability and HBD acidity followed by those containing formates and acetates. Almost all the PILs were found to have solvation properties comparable to water and single short chain alcohols like methanol and ethanol. The relative order of the IL polarities was similar for the solvatochromic and fluorescent probes. Through this study, in addition to the well-known distinct solvent properties of alkylammonium cation PILs, the high solvation capability of these PILs has been explicitly shown, which makes this class of ILs desirable for solvent-sensitive applications which require high polarity and H bonding ability.

High throughput approach to investigating ternary solvents of aqueous non-stoichiometric protic ionic liquids.

The use of ionic liquids (ILs) is limited for many applications due to their cost and/or viscosity. An efficient solution is to make mixtures of ILs with molecular solvents. However, it is well known that there are a large number of possible cation and anion combinations resulting in ILs, and this becomes a vast number when these are then combined with a molecular solvent. Therefore, we need structure-property relationships to design new IL-molecular solvent systems. In this work we have applied high throughput methods to investigate IL containing solutions to provide systematic data of a broad compositional space. We have principally focused on the surface tension, apparent pH and liquid nanostructure to identify potential self-assembly and protein stabilizing ability of solvent systems. Non-stoichiometric and aqueous IL-solvents were prepared in a high-throughput manner based on a deliberate experimental design approach such that 26 samples were prepared for each cation-anion-water combination. A selection of 8 protic ionic liquids (PILs) were used as starting materials, comprising ethanol-, ethyl-, butyl-, and pentylammonium cations combined with formate, acetate and nitrate anions. This resulted in a total of 208 different solvent systems. The measured solvent properties showed different trends in base-rich and acid-rich solvent combinations. Surface tensions of base-rich samples exhibited a relatively linear relationship with increasing excess amine, while acid-rich samples were more dominantly affected by the change in water content. Liquid nanostructure of acid-rich samples was retained upon water dilution, whereas a significant SAXS peak shift towards lower scattering angles was observed in the presence of excess amines, indicating larger nanosized aggregates were forming. The design of experiment approach used here is considered to be applicable to any multi-component solvent compositional space due to its suitability in using small data sets to cover large compositional spaces, and hence can be employed to decrease the time and sample quantities required.

Stability and activity of lysozyme in stoichiometric and non-stoichiometric protic ionic liquid (PIL)-water systems.

There has been a substantial increase in enzyme applications within the biochemical and pharmaceutical industries, for example, as industrial biocatalysts. However, enzymes have narrow marginal stability which makes them prone to become inactive and/or denature with a slight change in the solvent environment. Typically industrial applications require harsher solvent environments than enzyme native environments, and hence there is a need to understand solvent-protein interactions in order to develop strategies to maintain, or enhance, the enzymatic activity under industrially relevant solvent conditions. Previously we have shown that protic ionic liquids (PILs) with water can have a stabilising effect on lysozyme, with a large variation dependent on which PIL ions are present, and the water concentration [E. C. Wijaya et al., Phys. Chem. Chem. Phys. 18(37), 25926-25936 (2016)]. Here we extend on this work using non-stoichiometric aqueous PIL solvents to investigate, and isolate, the role of pH and ionicity on enzymes. We have used the PILs ethylammonium nitrate (EAN) and ethanolammonium formate (EOAF) since our previous work has identified these as good solvents for lysozyme. Solvent libraries were made from these two PILs with an additional precursor acid or base to modify the acidity/basicity of the neutral stoichiometric PIL, and with water added, to have solutions with 4-17 mol. % of the PIL ions in water. Molar ratios of base:acid were varied between 1:1.05 and 2:1 for EAN and 1:1.25 and 2:1 for EOAF, which enabled from highly basic to highly acidic solutions to be obtained. This was to modify the acidity/basicity of the neutral stoichiometric PILs, without the addition of buffers. The structure and stability of hen egg white lysozyme (HEWL) were explored under these solvent conditions using synchrotron small angle X-ray scattering (SAXS), Fourier transform infrared (FTIR), and activity assays. The radius of gyration and Kratky plots obtained from the SAXS data showed little change with varying ionicity or acid:base ratio. FTIR showed that α-helix was maintained in all, except for the most acidic solvent conditions. The activity data show that HEWL was active between pH 0 and 11 for the EA:N-water system and pH 4.4 and 11 for the EOA:F-water system. This work indicates that ionic liquids have the potential to enable enzymes to maintain activity across a broader range of solvent conditions.

How ionic species structure influences phase structure and transitions from protic ionic liquids to liquid crystals to crystals.

The phase behaviour of n-alkylammonium (C6 to C16) nitrates and formates has been characterised using synchrotron small angle and wide angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), cross polarised optical microscopy (CPOM) and Fourier transform infrared spectroscopy (FTIR). The protic salts may exist as crystalline, liquid crystalline or ionic liquid materials depending on the alkyl chain length and temperature. n-Alkylammonium nitrates with n ≥ 6 form thermotropic liquid crystalline (LC) lamellar phases, whereas n ≥ 8 was required for the formate series to form this LC phase. The protic ionic liquid phase showed an intermediate length scale nanostructure resulting from the segregation of the polar and nonpolar components of the ionic liquid. This segregation was enhanced for longer n-alkyl chains, with a corresponding increase in the correlation length scale. The crystalline and liquid crystalline phases were both lamellar. Phase transition temperatures, lamellar d-spacings, and liquid correlation lengths for the n-alkylammonium nitrates and formates were compared with those for n-alkylammonium chlorides and n-alkylamines. Plateau regions in the liquid crystalline to liquid phase transition temperatures as a function of n for the n-alkylammonium nitrates and formates are consistent with hydrogen-bonding and cation-anion interactions between the ionic species dominating alkyl chain-chain van der Waals interactions, with the exception of the mid chained hexyl- and heptylammonium formates. The d-spacings of the lamellar phases for both the n-alkylammonium nitrates and formates were consistent with an increase in chain-chain layer interdigitation within the bilayer-based lamellae with increasing alkyl chain length, and they were comparable to the n-alkylammonium chlorides.

Activity and conformation of lysozyme in molecular solvents, protic ionic liquids (PILs) and salt-water systems.

Improving protein stabilisation is important for the further development of many applications in the pharmaceutical, specialty chemical, consumer product and agricultural sectors. However, protein stabilization is highly dependent on the solvent environment and, hence, it is very complex to tailor protein-solvent combinations for stable protein maintenance. Understanding solvent features that govern protein stabilization will enable selection or design of suitable media with favourable solution environments to retain protein native conformation. In this work the structural conformation and activity of lysozyme in 29 solvent systems were investigated to determine the role of various solvent features on the stability of the enzyme. The solvent systems consisted of 19 low molecular weight polar solvents and 4 protic ionic liquids (PILs), both at different water content levels, and 6 aqueous salt solutions. Small angle X-ray scattering, Fourier transform infrared spectroscopy and UV-vis spectroscopy were used to investigate the tertiary and secondary structure of lysozyme along with the corresponding activity in various solvation systems. At low non-aqueous solvent concentrations (high water content), the presence of solvents and salts generally maintained lysozyme in its native structure and enhanced its activity. Due to the presence of a net surface charge on lysozyme, electrostatic interactions in PIL-water systems and salt solutions enhanced lysozyme activity more than the specific hydrogen-bond interactions present in non-ionic molecular solvents. At higher solvent concentrations (lower water content), solvents with a propensity to exhibit the solvophobic effect, analogous to the hydrophobic effect in water, retained lysozyme native conformation and activity. This solvophobic effect was observed particularly for solvents which contained hydroxyl moieties. Preferential solvophobic effects along with bulky chemical structures were postulated to result in less competition with water at the specific hydration layer around the protein, thus reducing protein-solvent interactions and retaining lysozyme's native conformation. The structure-property links established in this study are considered to be applicable to other proteins.

Micelle formation of a non-ionic surfactant in non-aqueous molecular solvents and protic ionic liquids (PILs).

Many ionic liquids and low molecular weight polar solvents have been reported to support amphiphile self-assembly, with most of these reported for the first time in the last decade. This phenomenon is attributed to the solvophobic effect (analogous to the hydrophobic effect in water). However, to date there has been no systematic study which evaluates micelle formation in a large library of non-aqueous solvents. Here we investigate micelle formation of a non-ionic amphiphile, hexa-ethyleneglycol mono n-dodecyl ether, C12E6, in a diverse range of molecular solvents and protic ionic liquids (PILs). Nine of the 19 non-aqueous molecular solvents investigated, and all four of the PILs, were found to support micelle formation. A link was investigated between the solvent cohesive energy density (as estimated using the Gordon parameter) and both the critical micelle concentration and the related free energy of micellization . In addition, the chemical structure and liquid mesostructure of the solvent were found to be important factors in the ability of the solvents to support micelle formation.

Controlling the characteristics of lamellar liquid crystals using counterion choice, fluorination and temperature.

The characteristics of robust and highly ordered fluorinated lamellar phases were explored as a function of temperature, counterion identity and fluorination of the surfactant and co-surfactant. Structural and composition effects were probed using a combination of small-angle scattering of X-rays and neutrons, polarising microscopy and calorimetry. It was found that in general, the phases remained remarkably stable with increasing temperature, showing only moderate loss of order and increased membrane flexibility. By changing the surfactant's cationic counterion, it was possible to exert influence on both the shape of micelles formed and the inter-layer spacing of the lamellar phases obtained. Ordering and crystallinity of the lamellar membranes could be controlled by the level of fluorination of both the surfactant and co-surfactant. These results suggest that subtle manipulations of selected control parameters including co-surfactant selection and counterion choice can provide a high level of control over membrane spacing and local order within lamellar phases, providing guidance where these materials are used as templates.