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

Myoview是一种99mTc的放射性药物，含有两种四磷蛋白配体；它在心脏的心肌细胞中积累，使得SPECT成像可以用于冠心病的诊断。双齿磷配体如四磷蛋白是强大的螯合剂，可以为放射性药物提供一个很好的平台。品客集团基于这一想法，通过氢化磷酸化来制备双牙膦，这种膦含有葡萄糖糖等靶向生物分子。本工作的目的是扩大靶向生物分子的范围，并通过氢化磷酸化反应设计新的多齿膦。然后，共轭配体将与放射性金属络合，并与伦敦国王学院的放射成像小组合作，作为放射性示踪剂进行筛选。此外，计算模型将用于研究铂(0)催化的不对称二膦活化烯烃的氢磷化反应。初步研究将集中于通过氢化反应合成四齿膦。高靶向性碳水化合物将被纳入这些支架中。该项目将涉及一系列技术，包括惰性气氛下的合成化学、放射化学标记实验和DFT计算。

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.