CAGE – a new generation IL. Using modelling to better understand complex molecule to molecule interactions in deep eutectic solvents and ionic liquids
File(s)
Author(s)
McKeever-Willis, Mikkaila
Type
Thesis
Abstract
CAGE (choline : geranate : geranic acid) is a novel IL with proven success in a broad range of pharmaceutical applications. The success of CAGE is likely due to specific molecular properties of the ternary system. This thesis uses DFT to investigate the conformational space of CAGE, component molecules and analogues to better understand the properties that lead to success.
CAGE was built up sequentially from the component structural motifs to molecules. For the choline cation, labelling with a positive charge localised on nitrogen is shown to be misleading. Individual molecules of geranic acid and composite carboxylic acids were investigated. For these carboxylic acids the folding and unfolding of the carbon chains are shown to be non-trivial processes. The folded conformer of the chain was found to be more stable in the gas phase (GP), modelling the lipophilic membrane, and the unfolded conformer more stable with an implicit water environment (AQ), modelling bulk aqueous biological fluid. Dimerisation of carboxylic acids show deviations from ideal hydrogen bonds which allow for the formation of multiple secondary hydrogen bonds.
For CAGE there are significant differences in low energy conformational space comparing GP and AQ results. GP-CAGE is dominated by a common conformer type with a strong central hydrogen bonding network across all three molecules, irrespective to the carboxylic acid in CAGE anion analogues. For AQ-CAGE the disruption of the cation-acid hydrogen bond is energetically accessible, opening up a much larger conformational space.
Overall this thesis presents a comprehensive exploration of the complex interactions and conformational space of CAGE, CAGE components and analogues. These results suggest that the conformation and interactions of CAGE are dependant on the surrounding environment, and the restrictions that arise due to the unsaturation and branching in the geranic acid chain are key to the unique behaviour of CAGE.
CAGE was built up sequentially from the component structural motifs to molecules. For the choline cation, labelling with a positive charge localised on nitrogen is shown to be misleading. Individual molecules of geranic acid and composite carboxylic acids were investigated. For these carboxylic acids the folding and unfolding of the carbon chains are shown to be non-trivial processes. The folded conformer of the chain was found to be more stable in the gas phase (GP), modelling the lipophilic membrane, and the unfolded conformer more stable with an implicit water environment (AQ), modelling bulk aqueous biological fluid. Dimerisation of carboxylic acids show deviations from ideal hydrogen bonds which allow for the formation of multiple secondary hydrogen bonds.
For CAGE there are significant differences in low energy conformational space comparing GP and AQ results. GP-CAGE is dominated by a common conformer type with a strong central hydrogen bonding network across all three molecules, irrespective to the carboxylic acid in CAGE anion analogues. For AQ-CAGE the disruption of the cation-acid hydrogen bond is energetically accessible, opening up a much larger conformational space.
Overall this thesis presents a comprehensive exploration of the complex interactions and conformational space of CAGE, CAGE components and analogues. These results suggest that the conformation and interactions of CAGE are dependant on the surrounding environment, and the restrictions that arise due to the unsaturation and branching in the geranic acid chain are key to the unique behaviour of CAGE.
Version
Open Access
Date Issued
2023-08-31
Date Awarded
2025-01-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Welton, Tom
Hunt, Patricia
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)