Calum J. Drummond

Protic Ionic Liquids: Evolving Structure–Property Relationships and Expanding Applications

The thermal and physicochemical properties of protic ionic liquids (PILs) are reported. It is highly evident that there has been an extensive range of alkylammonium, imidazolium, and heterocyclic cations paired with many organic and inorganic anions that have been employed to prepare PILs. There has been strong interest in modifying the properties of PILs through the addition of water or other molecular solvents. For many applications, the presence of some water in the PILs is not detrimental, and instead leads to enhanced solvent properties such as lower viscosity, higher conductivities, and lower melting points. It remains an issue of definition though of how to refer to these resulting protic solutions. There is also an ongoing difficulty surrounding how to describe the proton activity in the PILs, analogous to pH in aqueous systems. For a broad range of applications, it has been reported that the acidity/basicity of the PIL or PIL-solvent system is crucial for their beneficial properties. It is expected that the fundamental properties of PILs will continue to be explored, along with continued interest in many existing and new applications, such as in electrochemistry, organic and inorganic synthesis, and biological applications. In particular, there has been a significant interest in a broad- range of PILs for use as electrolytes and incorporation in polymer electrolytes for fuel cells, and other energy storage devices.

Ordered 2-D and 3-D nanostructured amphiphile self-assembly materials stable in excess solvent

Amphiphile lyotropic liquid crystalline self-assembly materials are being used for a diverse range of applications. Historically, the most studied lyotropic liquid crystalline phase is probably the one-dimensional (1-D) lamellar phase, which has been employed as a model system for biomembranes and for drug delivery applications. In recent years, the structurally more complex 2-D and 3-D ordered lyotropic liquid crystalline phases, of which reversed hexagonal (H(2)) and reversed cubic phases (v(2)) are two prominent examples, have received growing interest. As is the case for the lamellar phase, these phases are frequently stable in excess water, which facilitates the preparation of nanoparticle dispersions and makes them suitable candidates for the encapsulation and controlled release of drugs. Integral membrane protein crystallization media and templates for the synthesis of inorganic nanostructured materials are other applications for 2-D and 3-D amphiphile self-assembly materials. The number of amphiphiles identified as forming nanostructured reversed phases stable in excess solvent is rapidly growing. In this article, different classes of amphiphiles that form reversed phases in excess solvent are reviewed, with an emphasis on linking phase behavior to amphiphile structure. The different amphiphile classes include: ethylene oxide-, monoacylglycerol-, glycolipid-, phosphatidylethanolamine-, and urea-based amphiphiles.

Protic Ionic Liquids: Physicochemical Properties and Behavior as Amphiphile Self-Assembly Solvents

The physicochemical properties of 22 protic ionic liquids (PILs) and 6 protic molten salts, and the self-assembly behavior of 3 amphiphiles in the PILs, are reported. Structure-property relationships have been explored for the PILs, including the effect of increasing the substitution of ammonium cations and the presence of methoxy and hydroxyl moieties in the cation. Anion choices included the formate, pivalate, trifluoroacetate, nitrate, and hydrogen sulfate anions. This series of PILs had a diverse range of physicochemical properties, with ionic conductivities up to 51.10 mS/cm, viscosities down to 5.4 mPa.s, surface tensions between 38.3 and 82.1 mN/m, and densities between 0.990 and 1.558 g/cm3. PILs were designed with various levels of solvent cohesiveness, as quantified by the Gordon parameter. Fourteen PILs were found to promote the self-assembly of amphiphiles. High-throughput polarized optical microscopy was used to identify lamellar, hexagonal, and bicontinuous cubic amphiphile self-assembly phases. The presence and extent of amphiphile self-assembly have been discussed in terms of the Gordon parameter.

Nanostructured Protic Ionic Liquids Retain Nanoscale Features in Aqueous Solution While Precursor Brønsted Acids and Bases Exhibit Different Behavior

Small- and wide-angle X-ray scattering (SWAXS) has been used to investigate the effect that water has on the nanoscale structure of protic ionic liquids (PILs) along with their precursor Brønsted acids and bases. The series of PILs consisted of primary, secondary, and tertiary alkylammonium cations in conjunction with formate, nitrate, or glycolate anions. Significant differences were observed for these systems. The nanoscale aggregates present in neat protic ionic liquids were shown to be stable in size on dilution to high concentrations of water, indicating that the water is localized in the ionic region and has little effect on the nonpolar domains. The Brønsted acid-water solutions did not display nanostructure at any water concentration. Primary amine Brønsted bases formed aggregates in water, which generally displayed characteristics of poorly structured microemulsions or a form of bicontinuous phase. Exceptions were butyl- and pentylamine with high water concentrations, for which the SWAXS patterns fitted well to the Teubner-Strey model for microemulsions. Brønsted base amines containing multiple alkyl chains or hydroxyl groups did not display nanostructure at any water concentration. IR spectroscopy was used to investigate the nature of water in the various solutions. For low PIL concentrations, the water was predominately present as bulk water for PIL molar fractions less than 0.4-0.5. At high PIL concentrations, in addition to the bulk water, there was a significant proportion of perturbed water, which is water influenced in some way by the cations and anions. The molecular state of the water in the studied amines was predominately present as bulk water, with smaller contributions from perturbed water than was seen in the PILs.

A single spectroscopic probe for the determination of both the interfacial solvent properties and electrostatic surface potential of model lipid membranes

2,6-Diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenoxide, ET(30), has been investigated in order to ascertain its suitability as a probe for both the effective interfacial dielectric constant (Iµeff) and the electrostatic surface potential (ψ0) of model lipid membranes in aqueous solution. This work establishes that the solvatochromic visible absorption band for ET(30) can be used to provide a good estimate of the Iµeff for cationic micelles. It is also shown that the acid–base dissociation of ET(30) can be utilized to obtain a quantitative measure of the ψ0 in the case of cationic micelles. There are problems and uncertainties associated with the use of ET(30) in aqueous solutions of other types of charged self-assembled surfactant aggregates, and these are discussed.

Acid–base equilibria in aqueous micellar solutions. Part 1.—‘Simple’ weak acids and bases

The acid–base equilibria of a number of phenols, amines and carboxylic acids in aqueous micellar solutions and organic solvent–water mixtures have been examined. For the majority of the molecules investigated, the differences between the pKa values in pure water and the apparent pKa values when the molecules reside within micellar interfacial microenvironments can primarily be ascribed to the differenes between the mean intrinsic solvent properties of the interfacial and bulk phases, with an additional contribution from the electrostatic micellar surface potential in the case of the charged aqueous micellar solutions.

Observing self-assembled lipid nanoparticles building order and complexity through low-energy transformation processes.

Future nanoscale soft matter design will be driven by the biological paradigms of hierarchical self-assembly and long-lived nonequilibrium states. To reproducibly control the low-energy self-assembly of nanomaterials for the future, we must first learn the lessons of biology. Many cellular organelles exhibit highly ordered cubic membrane structures. Determining the mechanistic origins of such lipid organelle complexity has been elusive. We report the first observation of the complete sequence of major transformations in the conversion from a 1D lamellar membrane to 3D inverse bicontinuous cubic nanostructure. Characterization was enabled by adding a steric stabilizer to dispersions of lipid nanoparticles which increased the lifetime of very short-lived nonequilibrium intermediate structures. By using synchrotron small-angle X-ray scattering and cryo-transmission electron microscopy we observed and characterized initial lipid bilayer contacts and stalk formation, followed by membrane pore development, pore evolution into 2D hexagonally packed lattices, and finally creation of 3D bicontinuous cubic structures.

Lanthanide Oleates: Chelation, Self-assembly, and Exemplification of Ordered Nanostructured Colloidal Contrast Agents for Medical Imaging

Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T(1)) and transverse (T(2)) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.

Acid–base equilibria in aqueous micellar solutions. Part 3.—Azine derivatives

The acid–base behaviour of two azine derivatives, viz. neutral red and acridine, in aqueous non-ionic Brij-35 and n-octyl β-D-glucoside micellar solutions, in aqueous anionic sodium dodecyl sulphate micellar solutions and in 1,4-dioxane–water mixtures have been investigated. The factors primarily responsible for the difference between the pKavalue of an azine derivative in pure water and its apparent pKa value when it is located quantitatively within the micelle–aqueous solution interface have been determined. For the non-ionic micellar systems, the difference can be explained solely in terms of the different intrinsic solvent properties of the two solvating media. For the anionic micellar systems three major factors are considered to be responsible for the difference. These factors are the electrostatic micellar surface potential, the interfacial solvent characteristics, and specific molecular interaction between the cationic protonated moieties of the azine derivatives and the anionic surfactant headgroups.

High-throughput development of amphiphile self-assembly materials: fast-tracking synthesis, characterization, formulation, application, and understanding.

Amphiphile self-assembly materials, which contain both a hydrophilic and a hydrophobic domain, have great potential in high-throughput and combinatorial approaches to discovery and development. However, the materials chemistry community has not embraced these ideas to anywhere near the extent that the medicinal chemistry community has. While this situation is beginning to change, extracting the full potential of high-throughput approaches in the development of self-assembling materials will require further development in the synthesis, characterization, formulation, and application domains. One of the key factors that make small molecule amphiphiles prospective building blocks for next generation multifunctional materials is their ability to self-assemble into complex nanostructures through low-energy transformations. Scientists can potentially tune, control, and functionalize these structures, but only after establishing their inherent properties. Because both robotic materials handling and customized rapid characterization equipment are increasingly available, high-throughput solutions are now attainable. These address traditional development bottlenecks associated with self-assembling amphiphile materials, such as their structural characterization and the assessment of end-use functional performance. A high-throughput methodology can help streamline materials development workflows, in accord with existing high-throughput discovery pipelines such as those used by the pharmaceutical industry in drug discovery. Chemists have identified several areas that are amenable to a high-throughput approach for amphiphile self-assembly materials development. These allow an exploration of not only a large potential chemical, compositional, and structural space, but also material properties, formulation, and application variables. These areas of development include materials synthesis and preparation, formulation, characterization, and screening performance for the desired end application. High-throughput data analysis is crucial at all stages to keep pace with data collection. In this Account, we describe high-throughput advances in the field of amphiphile self-assembly, focusing on nanostructured lyotropic liquid crystalline materials, which form when amphiphiles are added to a polar solvent. We outline recent progress in the automated preparation of amphiphile molecules and their nanostructured self-assembly systems both in the bulk phase and in dispersed colloidal particulate systems. Once prepared, we can structurally characterize these systems by establishing phase behavior in a high-throughput manner with both laboratory (infrared and light polarization microscopy) and synchrotron facilities (small-angle X-ray scattering). Additionally, we provide three case studies to demonstrate how chemists can use high-throughput approaches to evaluate the functional performance of amphiphile self-assembly materials. The high-throughput methodology for the set-up and characterization of large matrix in meso membrane protein crystallization trials can illustrate an application of bulk phase self-assembling amphiphiles. For dispersed colloidal systems, two nanomedicine examples highlight advances in high-throughput preparation, characterization, and evaluation: drug delivery and magnetic resonance imaging agents.