富勒烯基核素促排剂的设计合成及构效关系研究

The main research objective of this project is to synthesize bifunctional chelates for metal nuclides through the bonding of fullerene with catechol or hydroxy pyridone. The new fullerene-based bifunctional chelates possess unusual abilities of both anti-free radicals and radionuclide chelating. In this issue, first, we design and synthesize the new fullerene-based radionuclide chelating agents to study the anti-free radicals ability and the chelating abilities of fullerene-based radionuclide chelating agents with the simulated nuclide Sr, Cs and U. Second, a wide-adaptability method to evaluate the chelation ability of fullerene-based radionuclide chelating agents in vitro is established. Third, the chelation effectiveness, anti-free radical ability and security of the obtained fullerene-based radionuclide chelating agents are evaluated. The end, the relationship of chelation effectiveness and the structure of fullerene-based radionuclide chelating agents is researched , which is anticipated to provide a deeper understanding of the chelation mechanism and internal rule at the molecular level. These results offer a more valuable theoretical and experimental basis to design and prepare the efficient bifunctional wide-adaptability radionuclide chelating agents in the further research.

本项目旨在将促排性能较好的邻苯二酚和羟基吡啶酮结构键联到具有"吸收自由基的海绵"之称的富勒烯结构上，制成一种兼具促排和抗自由基双重功能的核素促排剂。通过开展富勒烯基核素促排剂的设计合成，研究富勒烯基核素促排剂的抗自由基能力及其与模拟核素Sr、Cs和U的螯合能力。建立富勒烯核素促排剂体外广谱性评价方法，并对富勒烯基核素促排剂的促排效能、抗自由基能力以及安全性进行初步评价。研究富勒烯核素促排剂结构与促排效能的关系，揭示其内在规律，提出富勒烯基核素促排剂的促排机制，为下一步设计和制备出高效的双功能广谱性核素促排剂奠定理论基础和实验依据。

开展了系列富勒烯羟基吡啶酮衍生物和富勒烯邻苯二酚衍生物的设计、合成、分离纯化以及结构表征，获得了10种兼具有抗自由基和促排效能的富勒烯核素促排剂；采用电位滴定法、紫外分光光度法、荧光光谱法、等摩尔连续变化法（Job法）、SCP竞争络合法等方法研究了富勒烯核素促排剂样品与模拟核素铀、铯等的螯合能力以及K+、Ca2+、Mg2+和Zn2+等人体常见金属离子对富勒烯核素促排剂与UO22+络合的干扰作用，建立了富勒烯核素促排剂体外促排评价方法，并对富勒烯基核素促排剂的促排效能进行了评价；采用DPPH自由基法和超氧阴离子自由基法研究了所合成富勒烯基核素促排剂的清除自由基能力；分别采用MTT测试法和荧光标记计数法研究了所制备富勒烯核素促排剂对细胞株A549和L929的细胞毒性；根据所制备富勒烯核素促排剂的对核素和干扰离子的螯合能力、抗自由基能力以及细胞毒性等实验数据，探究了富勒烯核素促排剂的结构与促排效能的关系，提出了可能的络合机制、获得了相应的规律，为进一步设计合成更高效双功能核素促排剂提供数据和理论支撑。