富勒烯大环多胺衍生物的合成及其对铀的促排效果初探

The rapid development of nuclear energy and nuclear technology makes the actinides uranium use more and more widely, which resulted in increased the chance of nuclear accident. Accident caused by radiation not only displays direct illuminate to body surface, more serious is the internal irradiation. Once actinides into the body, the damage is mainly caused by free radicals' indirect damage which caused by nuclide decay emission radiation ionization, moreover also includes chemical toxicity of nuclide itself. One of the effective measures is to develop an efficient and low toxicity radionuclide chelating agents or blocking absorption agent. Although in recent years, there have been some clinical applications of ammonia mercapto, amine compounds, they exhibit good resistance to radiation damage effects, but they exit short duration of action, side effects and other shortcomings. Other new research to promote discharge agent also stay mostly in drug design, synthesis and pharmacodynamic evaluation, the depth of the research is not enough.Based on the fact that fullerene has a remarkable capability of clearing radicals, this work aims to modify fullerene to obtain soluble fullerene-derivative with a strong chelating function for uranyl ions. Through the study on its ability to eliminate radicals generated by ionizing irradiation and the behavior of chemical coordinating with uranium, this research aims to obtain physical and chemical parameters such as the coordination constant, stability constant, surface pH, apparent charge, solubility and lipid water partition, further to offer significant support for the study on biological property and characterization of fullerene-based amines as well as the research on effective uranium chelating agent.

锕系核素一旦进入人体，带来的伤害主要是由核素衰变发射射线电离产生的"自由基"引起的间接损伤，此外还包括核素本身的化学毒性。防护的有效措施之一是研制低毒高效的核素促排剂或阻吸剂。尽管近年来已有一些临床应用的氨巯基类、色胺类化合物等促排剂具有较好的抗辐射损伤的作用，但仍存在适用范围窄、有效作用时间短、毒副作用大等缺点。其他一些新的促排剂的研究还大多停留在药物设计、合成以及药效学的评价上，研究深度还不够。基于富勒烯具有很强的自由基清除功能，拟对富勒烯进行修饰，得到与铀酰离子具有较强螯合功能的水溶性富勒烯衍生物，研究其对电离辐射所产生的自由基的清除性能以及与铀的配位化学行为，通过上述研究，获取配合物的配位常数、稳定常数、表面酸碱度、表观电荷，以及溶解度、脂水分配系数等理化参数，为富勒烯基胺类化合物的生物学性质研究和性能表征，以及新型高效铀促排剂的研究提供重要支撑。

锕系核素一旦进入人体，带来的伤害主要是由核素衰变发射射线电离产生的“自由基”引起的间接损伤，此外还包括核素本身的化学毒性。防护的有效措施之一是研制低毒高效的核素促排剂或阻吸剂。尽管近年来已有一些临床应用的氨巯基类、色胺类化合物等促排剂具有较好的抗辐射损伤的作用，但仍存在适用范围窄、有效作用时间短、毒副作用大等缺点。其他一些新的促排剂的研究还大多停留在药物设计、合成以及药效学的评价上，研究深度还不够。本项目基于富勒烯具有很强的自由基清除功能，通过对富勒烯进行修饰，获得了克量级高纯度富勒烯基胺类衍生物，定性阐明了富勒烯基胺类衍生物与铀酰离子的配位行为；获得了富勒烯基胺类衍生物对小鼠体内铀促排及肝线粒体辐射损伤修复实验数据，证明了其作为铀核素促排剂以及辐射致损伤的修复剂的可行性，最终为新型富勒烯基胺类衍生物辐射防护制剂的研制和应用研究提供了基础数据。