Rotaxanes in lipid environments

O'Toole, R. C. P. (2025) Rotaxanes in lipid environments. PhD thesis, University of Reading. doi: 10.48683/1926.00127824

Abstract/Summary

Rotaxanes are a unique architecture in chemistry, consisting of two components—a thread and a macrocycle—which are bound together mechanically. The macrocycle can freely move along the thread structure, the motion of which can be modulated by structural adjustments of the individual components. This motion can be coupled to a secondary process to develop molecular machines, which have been used in catalysis and have potential applications as transmembrane therapeutics. Rotaxanes have been utilised as ion transporters, where the shuttling motion is theorised to ferry ions across the lipid bilayer. The rate of shuttling in these rotaxanes has been linked to their transport capabilities but have never been directly calculated in a lipid environment. In this thesis, a series of rotaxane anion carriers were developed, where shuttling away from the anion binding site was required for successful transmembrane transport. These rotaxanes were categorised into three shuttling regimes. The fastest shuttling rotaxane has transport capabilities most similar to its non-interlocked thread, and slower shuttling rotaxanes showed greater divergence. Novel variable-temperature (VT) transport experiments were carried out in two different membrane environments. In a more fluidic membrane, the transport rate of the rotaxanes increased more rapidly with temperature than the non-interlocked threads. Another set of rotaxanes were developed and their shuttling rate was directly monitored in a lipid environment using VT 19F NMR. An eight-fold reduction in shuttling rate was observed on going from solution to micellar state. The study is the first direct observation of shuttling rates of rotaxanes in lipid membranes, which is essential information required for the development of transmembrane molecular machinery based on the mechanical bond for biomedical applications and beyond.

Item Type	Thesis (PhD)
URI	https://centaur.reading.ac.uk/id/eprint/127824
Identification Number/DOI	10.48683/1926.00127824
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
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