Open-chain and macrocyclic multidentate phosphine ligands for radio-imaging and radiotherapy

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Myoview is a 99mTc radiopharmaceutical containing two tetrofosmin ligands; it accumulates in myocardial cells in the heart, allowing SPECT imaging to be used for the diagnosis of coronary heart disease. Bidentate phosphorus ligands like tetrofosmin are powerful chelators and could provide an excellent platform for radiopharmaceuticals. The Pringle group have built on this idea to prepare bidentate phosphines via hydrophosphination that contain targeting biomolecules such as glucosyl sugars. The aim of this work is to expand the scope of targeting biomolecules and design new multidentate phosphines via hydrophosphination reactions. The conjugated ligands will then be complexed to radiometals and screened as radiotracers in collaboration with the radioimaging groups in King's College London. Additionally computational modelling will be used to study the platinum(0)-catalysed hydrophosphination of activated alkenes by unsymmetrical diphosphines. Initial research will focus on synthesising tetradentate phosphines via hydrophosphination reactions. Highly targeting carbohydrates will then be incorporated into these scaffolds. This project will involve a range of techniques including synthetic chemistry under an inert atmosphere, radiochemical labelling experiments and DFT calculations.