The synthesis and study of novel fluorescence probes for Nitroreductase

This Thesis entitled ‘The synthesis and study of novel fluorescence probes for NTR’ is divided in 7 chapters. Chapter 1, provides an introduction to cancer, reductive stress and some techniques to detect the tumour cells. A range of relevant examples of fluorescence sensors for NTR are also given. This Chapter also includes the objectives for the research conducted in Chapters 2, 3 and 4. Chapter 2 describes the synthesis of a set of novel fluorescence sensors where variation of naphthalimide substituents is described. The synthesis of each compound is discussed, followed by an evaluation of their photophysical characteristics and response to nitroreductase (NTR) in a biological setting. Chapter 3 explores synthetic modifications to the compounds described in Chapter 2 in order to increase NTR sensitivity. A set of novel fluorescence sensors are described where the sensitivity is modulated using a range of reducible nitroaromatic moieties. The synthesis of each compound is also discussed, in addition to the preliminary test for NTR. Chapter 4 discusses a novel family of NTR sensors amenable to bioconjugation through various biocompatible linkages. Structural modification of compounds described in Chapter 2 provides access for conjugation to peptides, sugars, oligonucleotides and various other important biomolecules. The synthesis of each compound is discussed. Chapter 5 outlines the overall conclusion of the work carried out during this research. Chapter 6 describes general experimental procedures and the characterisation of each compound discussed throughout the thesis. Finally, in Chapter 7, the Appendix shows all supporting information