Water-soluble fullerenes and molecular machines: Supramolecular approaches to nanomedicine

Thesis

The incursion of the physical sciences into the medical sphere has led to myriad investigations in the use of nanomaterials for diagnostic and therapeutic purposes. In particular, the fullerenes show great promise in a number of areas because of their unique molecular properties. The chemistry of these carbon building blocks can be harnessed through covalent functionalisation and incorporation into supramolecular architectures such as extended self-assembled structures and molecular machines based on mechanically interlocked molecules. This thesis describes the synthesis and characterisation of such supramolecular structures incorporating fullerenes, whose potential utility in nanomedicine is demonstrated.

Water-solubilisation of fullerene C60 is achieved in the first part of this thesis by covalent functionalisation with triethylene glycol monoethyl ether. The resulting complex molecular structure is elucidated and a new method developed for interpreting elemental and thermal gravimetric analyses. It is highly soluble in water (37 mg/mL) and exhibits concentration-dependent photoluminescent behaviour suitable for biomedical applications. Ultraviolet-Visible absorption data points to the formation of self-assembled structures. Over time, these self-assembled structures grow considerably into hydrogels. Optical and scanning electron microscopies show the hydrogels have a tricontinuous hierarchical structure of great promise for use in drug delivery. The same functionalisation protocol is applied to higher fullerenes C70, C84 and C90–92, and extensive hierarchical structures are formed for the latter two. It is proposed that the presence of corannulene-like hydrophobic regions in the functionalised fullerenes affects the formation of hierarchical structures. Atomic force microscopy nanoindentation shows that the strongest of the formed hydrogels (C90–92 derivative, E = 432 ± 286 kPa) fares remarkably well against other supramolecular hydrogel competitors.

In the second part of this thesis, fullerene C60 is functionalised for incorporation into a rotaxane-based molecular machine. Two new iodo-alkyne functionalised fullerene derivatives are isolated in this process. C60 is incorporated into a four-station [3]rotaxane with two peripheral naphthalene diimide stations and two ferrocene-functionalised macrocycles via a copper-catalysed click reaction. The anion-induced motion of the macrocycles leads to a tuneable photoluminescent response due to photoinduced electron transfer. C60 plays a crucial electron-accepting role in this setup. In this way, this fullerene-containing mechanically interlocked architecture demonstrates a unique platform for the sensing of chloride ions. The utility of this [3]rotaxane is expanded into a theranostic tool by the demonstration of tuneable singlet oxygen generation by the central fullerene moiety concomitant with the tuneable photoluminescence.

Authors: Rasovic, I

• DOI: 10.5287/ora-nyoe1xexe
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: hydrogels; self-assembly; fullerenes; nanomedicine; supramolecular chemistry
• Subjects: Nanotechnology; Nanomaterials; Materials Science; Nanomedicine; Chemistry