Abstract
Chirality is ubiquitous in nature and biological systems, underpinning chemical processes that are fundamental to life. Although chirality in chemistry is typically associated with molecules containing chiral centres, this is not always the case. Helicenes are a class of aromatic molecules with a defining helical shape, giving rise to inherent chirality despite a lack of chiral centres. They have attracted considerable attention over the years due to their inherent chirality, in turn leading to applications in a diverse range of fields.While helicenes themselves are interesting synthetic targets, the design and synthesis of further topographically interesting, chiral molecules is of developing interest, molecular lemniscates, that is, molecules with a figure-eight shape, being an example of such. Although the intricate molecular design is, in itself, an appealing feature of these molecules, it is again the relationship between structural chirality and chiroptical properties that is prompting a current interest in these molecules. As such, the research within this thesis is directed towards the design and synthesis of new helicene-derived and lemniscular molecules to enable further investigation of their properties.
Chapter 1 provides an introduction to the field of helicene chemistry, discussing general properties, synthetic routes and applications of helicene-based structures. It also provides a literature background to molecular lemniscates, in which different classes of structures are discussed, including those derived from helicene scaffolds.
Chapter 2 is concerned with the design and synthesis of a [5]helicenoid structure which is used as the core scaffold throughout this thesis. The helical scaffold is formed via a [2 + 2 + 2] cycloisomerisation reaction, employing a diastereospecific point-to-helical chirality transfer strategy to control the sense of helical chirality, thus enabling the resolution free synthesis of enantiopure compounds. Structural and optical characterisation of this compound is also reported.
Chapter 3 explores the use of this [5]helicenoid scaffold in the development of a helicene-based self-assembly strategy for the synthesis of molecular lemniscates. This work demonstrates that homochiral helicene compounds can be coupled to form figure-eight molecules provided that suitable functionality is present, enabling a modular approach to their synthesis. In an initial proof-of-concept, two homochiral helicenes are linked via the formation of two azine motifs, leading to a figure-eight shaped molecule with D2 symmetry. To the best of our knowledge, this represents the first enantiopure route to helicene-derived molecular lemniscates.
Having established this strategy, Chapter 4 explores the versatility of the approach through reaction of the [5]helicenoid scaffold with a series of different dinucleophilic linker units. In particular, this work describes the self-assembly of hydrazone-based cyclobishelicenoids incorporating both rigid and more flexible linkers. Molecular structures of compounds generated from the coupling of the [5]helicenoid scaffold with aromatic acyl dihydrazides were determined by single-crystal X-ray diffraction, providing unambiguous evidence of the anticipated lemniscular shape.
While helicene molecules have found many applications, Chapter 5 focuses upon investigating the potential biological applications of the core [5]helicenoid scaffold described throughout this work. As such, this chapter describes the derivatisation of the scaffold to generate molecules suitable for use as ligands for G-quadruplex DNA. Investigation into their ability to stabilise two G-quadruplex sequences (h-TELO and TBA) demonstrate strong enantioselective behaviour.
Finally, Chapter 6 provides brief concluding remarks on the work presented within this thesis as well as suggested directions for future work.
| Date of Award | 28 Jun 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Dan Pantos (Supervisor) & Simon Lewis (Supervisor) |