الفهرس 
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Abstract
DISSERTATION TITLE The synthesis and study of fluorescent dendritic molecules Researchers in visualisation and diagnostic imaging for biological applications regard water soluble fluorescent dendrimers as potentially useful materials. Described in this thesis is research with the aim of preparing and investigating a new series of fluorescent polyamidoamine (PAMAM) dendrons with an imidazole naphthalimide derivative (i.e. 7H-benz[de]benzimidazo[2,1-a]isoquinoline-7-one ) as the fluorescent core. After an introduction to the use of dendrimers and dendritic compounds in biology (Chapter 1), we describe work to prepare and optimise potential fluorophore cores, which are based on N-alkylamino, N-arylamino or imidazole naphthalimide derivatives (Chapter 2). The fluorescence intensity of most of these aromatic systems is weak due to the efficient intramolecular photoinduced electron transfer process (PET). However, derivatives of 7H-benz[de]benzimidazo[2,1-a]isoquinoline-7-one proved encouraging and it was decided to use this readily modifiable fluorophore as the core in the design of highly fluorescent dendrons. In the second experimental part of the thesis (Chapter 3), we designed and prepared several new water soluble fluorescent PAMAM dendrons based on 7H-benz[de]benzimidazo[2,1-a]isoquinoline-7-one as fluorescent core and studied their photochemical and physicochemical properties. The dendrons are all fluorescent due to the core but in some cases this is modulated by the PET process, which increases with higher PAMAM dendron generation. For all dendrons the fluorescence is linearly correlated with concentration and the pH of the aqueous solvent has a significant effect for both UV absorbance (ground state) and fluorescent emission (excited state). In strong acidic media this is due to protonation of the core, while in basic media the fluorescent emission is quenched due to presence of the PET process involving the tertiary amine groups within the PAMAM units. The strongest fluorescent emission of all carboxylate-terminated dendrons was pH 6. Physicochemical studies using the Pulsed Gradient Spin Echo Nuclear Magnetic Resonance (PGSE-NMR) technique indicate that the self-diffusion coefficient and hydrodynamic radii are unaffected by concentration suggesting that there is no aggregation. The confirmed properties (i.e. water solubility, high fluorescence at near neutral pH, and no aggregation) suggest these new dendrons are promising for applications in biological studies. The next part of the thesis describes new avenues of research using these dendrons and similar materials are suggested in the final chapter (Chapter 5). Finally, the appendix part of the thesis describes experimental work to assess the transport of the dendrons through biological barriers and their binding to DNA (Appendix A). This work was carried out in collaboration with other research groups. Initial studies suggest that the permeability of fluorescent core PAMAM dendrons across MDCK cell monolayers appear to be a function of the size of the dendrons. These studies pave the way for future detailed mechanistic and morphological studies to elucidate the nature of the interaction of fluorescent core PAMAM dendrons with epithelial cells. Preliminary studies also show that the fluorescent core binds to DNA, presumably by intercalation of the aromatic core. Addition of negatively charged dendrons results in a strong decrease in affinity for DNA. The affinity is not restored by esterification, highlighting contributions of both electrostatic repulsion but particularly steric interactions in blocking interactions. Coupling the fluorescent core to positively charged dendrons leads to strong binding accompanied by precipitation of the DNA complex.