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Air-stable fluorescent primary phosphines and their potential applications as precursors for disease imaging agents

The low air stability of many primary phosphines has made them an under-utilised class of ligand, however they are versatile starting materials due to the possibility of functionalising the weak phosphorus hydrogen bonds, which can lead to a library of new phosphorus compounds. The work presented herein details the synthesis of the first air-stable fluorescent primary phosphines based on the fluorophore Bodipy (Chapter 2). The primary phosphines are shown to be air-stable in solution and in the solid state by 31P NMR spectroscopy and by DFT computational analysis, which is in accord with our group’s model of phosphine air-stability. In Chapters 3 and 4 we show the primary phosphines can be readily functionalised via hydrophosphination and formylation reactions to give novel fluorescent tertiary monodentate and tridentate derivatives. Fluorescent primary phosphines and their functionalisation via hydrophosphination reactions. Remarkably the phosphorus moieties have minimal influence on the photophysical properties, showing only a slight reduction in fluorescence quantum yields from the parent Bodipy dyes; the fluorescence is not ‘switched off’, which is the case for many amines and the few examples of phosphines conjugated to other fluorophores. In Chapter 4 we show these novel fluorescent phosphines coordinate to a range of low oxidation state(I-III) transition metals including those in groups 6, 9, 10 and 11. Surprisingly the presence of the heavy metals does not turn off the emission of the Bodipy dye; the complexes also showed high thermal and air stability in solution. These complexes have the potential to be used as multi-functional radiopharmaceutical complexes, for which the following functions were sought after (i) a polydentate ligand to ensure the complex is kinetically inert and thermodynamically stable; (ii) a radioactive metal centre, which will allow in vivo nuclear imaging using a gamma scanner; (iii) a fluorophore, which will provide in vitro fluorescence imaging and (iv) a target-specific group to transport the radiolabel to a specific receptor site in the body for iii a given disease. This combination of modalities would allow images obtained from fluorescence cell imaging to be correlated with in vivo radioimaging, to gain a greater understanding of the true fate of these agents within the body. The last chapter shows how the fluorescent rhenium(I) phosphine complexes can be made target-specific, and details the synthesis of a 99mTc radio-analogue containing a fluorescent tridentate phosphine rhenium(I) centre, which showed high levels of stability in biological media. Fluorescent rhenium(I) phosphine complexes, which have a carboxylic acid tag for peptide coupling, allowing the preparation of a target-specific fluorescent potential radiopharmaceutical, and a 99mTc/Re(I) fluorescent tridentate phosphine complex. Finally a number of the complexes are uptaken into cervical and prostate cancer cells and viewed by fluorescence confocal microscopy. Most of the complexes showed no toxicity towards the cells and have the potential to be used as a diagnostic tool.
Date January 2013
CreatorsDavies, Laura Helen
PublisherUniversity of Newcastle upon Tyne
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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