To separate and bind: Chelators for extraction and stable coordination of radioactive metal ions

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This project aims to develop new chelators that can: (i) selectively coordinate medically useful radioactive metal ions that are present in legacy nuclear waste; (ii) stably coordinate these medically useful isotopes to enable application in molecular radiopharmaceuticals; (iii) be functionalised for attachment to either resins for solid-phase extraction purposes, or biologically active groups (e.g. peptides) for disease targeting.This project will feature the chelate design and synthesis of a range of radionuclides for which previously very little ligand chemistry has been developed, and are situated towards the lower end of the periodic table e.g. Ra-223, Pb-212, Ac-225 and Th-227 and present in legacy nuclear waste. These radioisotopes offer a range of imaging, diagnostic and therapeutic properties which have currently been underutilised by the lack of suitable chelators, and the lack of availability of the radioisotopes themselves. Many of these metals have been utilised in their simple halide, nitrate or hydroxide compound state, but there is a real dearth of stable chelate complexes known in the literature. In this project, the student will prepare a range of macrocyclic 'crown' ligands featuring a range of donor heteroatoms either within the ring system or as pendant groups, which can enable a tailoring of the 'hard-soft' nature of the radiometals - and application in solid phase extraction experiments at NNL. The most promising chelators will be chosen to take forward for bioconjugation to a peptide or antibody, and subjected to a range of radiolabelling, in vitro and in vivo experiments to evaluate the biological efficacy of these new, targeted radiotracers.