Danielle F. Kennedy

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.

Gas‐Separation Membranes Loaded with Porous Aromatic Frameworks that Improve with Age

Porosity loss, also known as physical aging, in glassy polymers hampers their long term use in gas separations. Unprecedented interactions of porous aromatic frameworks (PAFs) with these polymers offer the potential to control and exploit physical aging for drastically enhanced separation efficiency. PAF-1 is used in the archetypal polymer of intrinsic microporosity (PIM), PIM-1, to achieve three significant outcomes. 1) hydrogen permeability is drastically enhanced by 375% to 5500 Barrer. 2) Physical aging is controlled causing the selectivity for H2 over N2 to increase from 4.5 to 13 over 400 days of aging. 3) The improvement with age of the membrane is exploited to recover up to 98% of H2 from gas mixtures with N2 . This process is critical for the use of ammonia as a H2 storage medium. The tethering of polymer side chains within PAF-1 pores is responsible for maintaining H2 transport pathways, whilst the larger N2 pathways gradually collapse.

Lithiated Porous Aromatic Frameworks with Exceptional Gas Storage Capacity

Kristina Konstas, James W. Taylor, Aaron W. Thornton, Cara M. Doherty, Wei Xian Lim, Timothy J. Bastow, Danielle F. Kennedy, Colin D. Wood, Barry J. Cox, James M. Hill, Anita J. Hill, Matthew R. Hill

High throughput preparation and characterisation of amphiphilic nanostructured nanoparticulate drug delivery vehicles.

The preparation, characterisation and assessment of drug delivery vehicles is typically a slow and complex process. Here we present a nanostructured nanoparticle system that can be prepared and characterised in a high-throughput fashion. In particular we use phytantriol and Myverol to prepare inverse bicontinuous cubic and inverse hexagonal liquid crystalline nanoparticles loaded with 10 commonly used therapeutic agents at increasing concentration. The dispersions are prepared using automated apparatus to create different concentrations and phases using novel protocols. We are able to characterise each stabilised nanoparticle dispersion using a range of methodologies including small angle X-ray scattering, particle sizing and drug partitioning. With this information we are able to assess which drug delivery vehicle is preferred for each drug and at which concentration the drug should be loaded to ensure maximum payload and to retain particle integrity.

Protic ionic liquids with fluorous anions: physicochemical properties and self-assembly nanostructure

A series of 11 new protic ionic liquids with fluorous anions (FPILs) have been identified and their self-assembled nanostructure, thermal phase transitions and physicochemical properties were investigated. To the best of our knowledge this is the first time that fluorocarbon domains have been reported in PILs. The FPILs were prepared from a range of hydrocarbon alkyl and heterocyclic amine cations in combination with the perfluorinated anions heptafluorobutyrate and pentadecafluorooctanoate. The nanostructure of the FPILs was established by using small- and wide-angle X-ray scattering (SAXS and WAXS). In the liquid state many of the FPILs showed an intermediate range order, or self-assembled nanostructure, resulting from segregation of the polar and nonpolar hydrocarbon and fluorocarbon domains of the ionic liquid. In addition, the physicochemical properties of the FPILs were determined including the melting point (T(m)), glass transition (T(g)), devitrification temperature (T(c)), thermal stability and the density ρ, viscosity η, air/liquid surface tension γ(LV), refractive index n(D), and ionic conductivity κ. The FPILs were mostly solids at room temperature, however two examples 2-pyrrolidinonium heptafluorobutyrate (PyrroBF) and pyrrolidinium heptafluorobutyrate (PyrrBF) were liquids at room temperature and all of the FPILs melted below 80 °C. Four of the FPILs exhibited a glass transition. The two liquids at room temperature, PyrroBF and PyrrBF, had a similar density, surface tension and refractive index but their viscosity and ionic conductivity were very different due to dissimilar self-assembled nanostructure.

Metal-free and MRI visible theranostic lyotropic liquid crystal nitroxide-based nanoparticles.

The development of improved, low toxicity, clinically viable nanomaterials that provide MRI contrast have tremendous potential to form the basis of translatable theranostic agents. Herein we describe a class of MRI visible materials based on lyotropic liquid crystal nanoparticles loaded with a paramagnetic nitroxide lipid. These readily synthesized nanoparticles achieved enhanced proton-relaxivities on the order of clinically used gadolinium complexes such as Omniscan™ without the use of heavy metal coordination complexes. Their low toxicity, high water solubility and colloidal stability in buffer resulted in them being well tolerated in vitro and in vivo. The nanoparticles were initially screened in vitro for cytotoxicity and subsequently a defined concentration range was tested in rats to determine the maximum tolerated dose. Pharmacokinetic profiles of the candidate nanoparticles were established in vivo on IV administration to rats. The lyotropic liquid crystal nanoparticles were proven to be effective liver MRI contrast agents. We have demonstrated the effective in vivo performance of a T1 enhancing, biocompatible, colloidally stable, amphiphilic MRI contrast agent that does not contain a metal.

Lanthanide Phytanates: Liquid-Crystalline Phase Behavior, Colloidal Particle Dispersions, and Potential as Medical Imaging Agents

Lanthanide salts of phytanic acid, an isoprenoid-type amphiphile, have been synthesized and characterized. Elemental analysis and FTIR spectroscopy were used to confirm the formed product and showed that three phytanate anions are complexed with one lanthanide cation. The physicochemical properties of the lanthanide phytanates were investigated using DSC, XRD, SAXS, and cross-polarized optical microscopy. Several of the hydrated salts form a liquid-crystalline hexagonal columnar mesophase at room temperature, and samarium(III) phytanate forms this phase even in the absence of water. Select lanthanide phytanates were dispersed in water, and cryo-TEM images indicate that some structure has been retained in the dispersed phase. NMR relaxivity measurements were conducted on these systems. It has been shown that a particulate dispersion of gadolinium(III) phytanate displays proton relaxivity values comparable to those of a commercial contrast agent for magnetic resonance imaging and a colloidal dispersion of europium(III) phytanate exhibits the characteristics of a fluorescence imaging agent.

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.

Amino Acid-derived Protic Ionic Liquids: Physicochemical Properties and Behaviour as Amphiphile Self-assembly Media

The thermal phase transitions and physicochemical properties of a series of 21 amino acid-derived protic ionic liquids and four protic molten salts have been investigated. Structure–property comparisons for this series were investigated for alkyl- and cyclic amino acid cations, and ethoxy and methoxy groups on the cation, combined with nitrate or various carboxylate-containing anions. All the protic fused salts were found to be ‘fragile’. Most of the protic fused salts exhibited a glass transition, with the transition temperatures ranging from –90° to –42°C. Viscosities and conductivities ranged from 0.03 to 15.46 Pa s and 0.02 to 2.20 mS cm–1 at 25°C respectively. The protic ionic liquids alanine methyl ester glycolate, proline methyl ester nitrate, and proline methyl ester glycolate were found to be capable of supporting amphiphile self-assembly. Lamellar or hexagonal liquid crystalline phases were observed with the cationic surfactant hexadecyltrimethylammonium bromide and the non-ionic surfactant Myverol 18–99K.

Amphiphilic oligoether-based ionic liquids as functional materials for thermoresponsive ion gels with tunable properties via aqueous gelation

The aqueous gelation of an amphiphilic ammonium oligoether-based ionic liquid (AMMOENG 102) is addressed and compared to the gelation of a similar compound (AMMOENG 100) recently reported (J. Casamada Ribot, C. Guerrero-Sanchez, R. Hoogenboom and U. S. Schubert, J. Mater. Chem., 2010, 20, 8279.).1 The comparison is based on proton nuclear magnetic resonance spectroscopy, rheological, ionic conductivity, water uptake, differential scanning calorimetry, surface tension and small angle X-ray scattering investigations. The results demonstrate that slight changes in the chemical structure of these ionic liquids can have an important effect on the properties of their corresponding ion gels. Hence, this contribution provides an insight into the stability and formation mechanism of these new ion gels solely consisting of ionic liquid and water and expands the range of amphiphilic ionic liquids which can be utilized for the straightforward and inexpensive preparation of thermoresponsive materials with tunable properties (i.e., ionic conductivity and melting point) and high mechanical moduli.