EAPSI: Synthesis and Characterization of Metal-Based Imaging and Therapeutic Agents

金属离子，特别是铁离子和铂离子，在医学领域具有重要的诊断和治疗作用。大多数磁共振成像（MRI）试剂以金属离子为特征。一些放射性金属用于诊断成像，而另一些则可用于化疗，向肿瘤提供局部辐射，最大限度地减少对健康组织的损害。为了将这些金属用于医学应用，将制备一种具有柔性臂的分子，能够包裹金属离子。这些实验将在新西兰奥克兰大学与金属医学领域的专家佩内洛普·兄弟博士合作进行。这些化合物作为光动力治疗（PDT）光敏剂和MRI造影剂的潜力将分别在奥克兰大学光子工厂激光实验室和高级MRI中心进行研究。随着新化合物的开发，更有效的治疗方法或更敏感的显像剂将改善全球患者的预后。该项目将开发新的尖桩栅栏配体，适用于各种应用的生物相关金属离子的配位：PDT， α -放疗，β -放疗和MRI。在这个motif中，corrole macrocycle将被附加有灵活的臂，可以快速和紧密地协调一个金属中心。这些化合物的配位化学将与各种金属进行研究，这些金属的配合物很少或不存在，包括铋、铼、钆和其他镧系元素。最后，当暴露于模拟生物环境的条件下，例如还原硫醇，将评估金属配合物的稳定性。NSF EAPSI奖是与新西兰皇家学会合作资助的。

Metal ions, particularly iron and platinum, have an important role as both diagnostic and therapeutic agents in the field of medicine. The majority of magnetic resonance imaging (MRI) agents feature a metal ion. Some radioactive metals are used for diagnostic imaging, while others can be used for chemotherapy, delivering localized radiation to a tumor and minimizing damage to healthy tissue. In order to exploit these metals for medical applications, a molecule with flexible arms capable of wrapping around a metal ion will be prepared. These experiments will be carried out at the University of Auckland in New Zealand in collaboration with Dr. Penelope Brothers, an expert in the field of metal-based medicine. The potential of these compounds as photosensitizers for photodynamic therapy (PDT) and contrast agents for MRI will be studied at the University of Auckland Photon Factory laser laboratory and the Centre for Advanced MRI, respectively. With the development of new compounds, therapeutics with greater efficacy, or imaging agents with better sensitivity, will improve patient outcomes across the globe. This project will exploit novel picket-fence corrole ligands that are amenable to the coordination of biologically relevant metal ions for a variety of applications: PDT, alpha-radiotherapy, Beta-radiotherapy, and MRI. In this motif, the corrole macrocycle will be appended with flexible arms that can rapidly and tightly coordinate a metal center. The coordination chemistry of these compounds will be studied with a variety of metals for which corrole complexes are rare or nonexistent, including bismuth, rhenium, gadolinium, and other lanthanides. Finally, the stability of the metal complexes will be evaluated when exposed to conditions, such as reducing thiols, which mimic a biological environment. This NSF EAPSI award is funded in collaboration with the Royal Society of New Zealand.