Ana DOBRE1, Daniel RAUBER2, Nicholas J. BROOKS1, Tom WELTON1
1Department of Chemistry, Imperial College London, London, United Kingdom
2Department of Chemistry, Saarland University, Saarbrücken, Germany
Ionic liquids (ILs) and deep eutectic solvents (DESs) are becoming increasingly popular as sustainable solvents, mainly because they fall into the category of “designer solvents”. This means that the properties of an IL or DES can be tailored to suit specific applications by changing the structure of the system’s constituent species. One area where interest in ILs and DESs is rapidly increasing is drug formulation and delivery within the pharmaceutical industry.
Choline-and-geranate (CAGE) is a DES comprised of choline, geranate and geranic acid that has shown promise as a transdermal drug delivery agent. Despite its potential, CAGE has several drawbacks that may discourage its use on an industrial scale. Geranic acid is commercially available only as an isomer mixture and its purification requires a lengthy, solvent-intensive process. CAGE itself is hygroscopic and heat-sensitive; this makes it difficult to store and could lead to inconsistencies in pharmaceutical formulations.
This project aims to understand the effects of specific structural features on the properties of CAGE-like DESs. Structural analogues of CAGE were selected using a targeted modification approach, where the hydrogen bonding ability of the cation (via a hydroxyl group) and the branching and unsaturation of the acids were varied. The properties, structuring and thermal behaviour of these DESs were investigated using a range of techniques, including small- and wide-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and polarised-light microscopy.
CAGE is an isotropic liquid with a weakly-ordered structure, arising from the ionic and hydrogen-bonding interactions of its constituents. When octanoic acid was used instead of geranic acid, the systems obtained showed significantly different behaviours. Two such DESs were synthesised, one containing a choline cation (CAOC) and one containing a butyltrimethylammonium cation (BTMAAOC). Both formed lamellar liquid-crystals which were found to undergo a liquid-liquid phase transition to an isotropic liquid phase. The formation of highly ordered bilayers is likely to be a result of the acid structure, which lacks the branching and unsaturation of geranic acid and is therefore less sterically demanding. This suggests that the acid structure plays a crucial role in the ordering, and thus the behaviour, of the system. It is also important to note that the liquid-liquid phase transition occurs at a higher temperature for CAOC than for BTMAAOC; this shows that the increased hydrogen bonding in CAOC (which contains a choline cation) helps stabilise the liquid crystal phase. Showcasing the effect of the acid, anion and cation structures on the DES properties is an important first step in understanding the structure-property relationships in CAGE-like systems.