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

用于放射成像和放射治疗的开链和大环多齿膦配体

• 批准号: 2742063
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2742063
• 关键词: Open; chain; macrocyclic; multidentate; phosphine

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.

Myoview是一种含有两种替曲膦配体的99 mTc放射性药物;它在心脏的心肌细胞中积累，允许SPECT成像用于诊断冠心病。双齿磷配体如替曲膦是强有力的螯合剂，可以为放射性药物提供极好的平台。Pringle小组基于这一想法，通过氢化膦化制备了含有靶向生物分子（如葡萄糖基糖）的双齿膦。本工作的目的是扩大靶向生物分子的范围，并通过氢化膦化反应设计新的多齿膦。然后将共轭配体与放射性金属络合，并与伦敦国王学院的放射成像组合作筛选为放射性示踪剂。此外，计算模型将用于研究铂（0）催化的不对称双膦的活化烯烃的氢膦化。初步研究将集中在通过氢化膦化反应合成四齿膦。然后将高度靶向的碳水化合物掺入这些支架中。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。