基于Xe的穴蕃体系磁共振分子探针的设计、合成及性质研究

本项目拟设计并合成一系列能够有效结合Xe 原子，并具有肿瘤细胞靶向性的磁共振分子探针，用于肿瘤细胞的早期检测。在相同浓度下，超极化Xe 的NMR 灵敏度比传统质子NMR 高10000 倍以上，但作为惰性元素的单原子Xe 不具有靶向性，只有自由Xe 的单一NMR 信号。若超极化Xe 与笼状穴蕃衍生物的超分子主体单元结合后，Xe 的化学位移便发生改变，能获得自由Xe 和结合Xe 两种不同的NMR 信号，从而可利用超极化Xe 的NMR 高灵敏度。因此，以绿色化学思想为指导，设计合成能有效结合Xe原子的穴蕃主体，是本项目的关键之一。此外，若在此穴蕃主体分子上，修饰酪氨酸激酶抑制剂中4-苯胺喹唑啉结构作为识别位点，便能使该分子探针同时具有对肿瘤细胞的靶向性；其中，以葡萄糖、肽等水溶性基团将穴蕃主体与4-苯胺喹唑啉结构通过化学键桥联起来，将有利于提高此分子探针的水溶性与生物兼容性，扩展其潜在应用范围。

The project design and synthesize a class of molecular probes,which can hold Xe atom and target the tumor cells to achieve the purpose of tumor cell early detection. Under the same concentration, the NMR sensitivity of hyperpolarized Xenon will be 10000 times higher than the classical NMR of hydrogen. But the xenon doesn't have targeting property as a inert element, only has one NMR signal of free Xenon. When the hyperpolarized Xenon bind with cryptophane cage effectively, the chemical shift of Xenon will be changed and cause one more NMR signal of binding Xenon. As a result, the ultrasensitivity of hyperporlarized Xenon can be used by the molecular probe. So design and synthesis of the cryptophane host unit, whose cavity structure, size, and intramolecular forces are all fit the hydrophobic Xe atom, is one of the key technologies of this project. When modify the 4-anilinoquinazoline moiety in tyrosine kinase inhibitor to the cryptophane as binding site, the molecular probe will have tumor cell target property. At the same time, the water-soluble modification using peptide or glucose will also promote the biocompatibility of the molecular probes, which will make the molecular probe more helpful.