Synthesis of photocleavable supramolecular rotaxanes towards the controlled binding of nucleic acid three-way junctions

Hooper, Catherine Amelia Josephine (2024). Synthesis of photocleavable supramolecular rotaxanes towards the controlled binding of nucleic acid three-way junctions. University of Birmingham. Ph.D.

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Abstract

This work aimed to develop a supramolecular system which is responsive to an external trigger for the controlled formation of nucleic acid three-way junctions. Metallo-helicates capable of junction formation were modified with photocleavable capping groups and encapsulated in cucurbit[10]uril rings to form supramolecular rotaxanes. Removal of the capping groups by irradiation for the release of the metallo-helicate to trigger junction formation was investigated.
In Chapter 2, the structure of an imidazole-based nickel helicate is modified to include a photocleavable protecting group. Synthesis of a supramolecular rotaxane is then attempted via two different pathways. The photocleavage and junction binding of the nickel complexes are investigated by UV-visible spectroscopy, mass spectrometry, and polyacrylamide gel electrophoresis in Chapter 3.
Alternative designs for supramolecular rotaxanes are detailed in Chapters 4 and 5 where the terminal imidazole rings of the helicates investigated in Chapters 2 and 3 are exchanged for 4- and 5-hydroxypyridines. The formation of supramolecular rotaxanes from the 4- and 5-hydroxypyridine based helicates with photocleavable capping groups is then investigated. Chapter 5 also includes the synthesis of a 3- hydroxypyridine based metal helicate designed to permit the control of junction binding activity without encapsulation in the cucurbit[10]uril macrocycle.
The removal of the capping groups from the hydroxypyiridne-based complexes in response to irradiation is then explored by UV-visible spectroscopy and mass spectrometry in Chapter 6. The formation of nucleic acid three-way junctions by the 5- hydroxypyridine based complexes is then investigated by polyacrylamide gel electrophoresis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):