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

Myoview是一种99mTc放射性药物，含有两个Tetrofosmin配体；它在心脏的心肌细胞中蓄积，使SPECT成像可以用于诊断冠心病。双齿磷配体，如四氧磷明，是强有力的螯合剂，可以为放射性药物提供一个很好的平台。Pringle团队在这一想法的基础上，通过氢化磷化反应制备了双齿膦，这种膦含有葡萄糖等靶向生物分子。这项工作的目的是扩大靶向生物分子的范围，并通过氢化磷化反应设计新的多齿膦。然后，与伦敦国王学院的放射成像小组合作，将共轭配体与放射性金属络合，作为放射性示踪剂进行筛选。此外，还将使用计算模型来研究铂(0)催化的不对称双膦催化活性烯烃的氢磷化反应。初步研究将集中在通过氢磷化反应合成四齿膦。然后，高度靶向的碳水化合物将被结合到这些支架中。该项目将涉及一系列技术，包括惰性大气下的合成化学、放射化学标记实验和密度泛函计算。

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.