Chiral separations using chiral amino acid ionic liquids

• Main Author: McCarron, Philip
• Published: Queen's University Belfast 2016
• Subjects: 615
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707833

The backbone of this work is to make a chiral ionic liquid with enantioselective properties. It is envisaged that the ionic liquid will be a component part of a gel matrix, or membrane, which holds a racemic drug in solution, and shows preferential affinity to one enantiomer. This would allow favoured diffusion of the unattached enantiomer, and such a system would be ideal as the reservoir in a drug delivery system. To test this idea, chiral amino acid ionic liquids were used. The thesis introduces ionic liquids by definition, classification, properties and industrial applications, and also the anti-inflammatory drug ibuprofen as the model test compound. The main application, discussed in Chapter 2, was the separation of ibuprofen enantiomers using chiral amino acid ionic liquids as the chiral selector with liquid-liquid extractions. Ionic liquid preparation is included in Chapter 3, as is an overview of HPLC analysis. Chiral interactions may depend on many factors, and these are explained in Chapter 4. Interaction experiments were performed, and techniques complementary to HPLC also explored. Chapter 5 highlights the subtle nature of enantiomeric separations. Here, an increase in enantiomeric excess percentage by physical processes was demonstrated using ionic liquid test strips. They were developed to help determine enantiomeric excess of ibuprofen as it passed through a series of ionic liquid impregnated sections on paper or silica. In Chapter 6, the analytical and preparative technique of countercurrent chromatography is discussed. It concludes with an application that used a thiouronium based ionic liquid to resolve racemic mandelic acid. Overall, the aim was not to develop and optimise a specific application, but to demonstrate proof-of-principle for using chiral ionic liquids to achieve enantiomeric separation. Two new methodologies were unambiguously demonstrated: the use of paper strips and countercurrent chromatography, and both appear to be worthy of future development.