含蒽大环多胺的合成及其对核苷酸的识别和传感研究

The development of receptors for nucleotides and study their molecular recognition are highly important due to their biological significance. However, the strong hydration of these anions in water and the structural similarity of the phosphate anion family, make the creation of highly selective and sensitive receptors for nucleotides in aqueous solution highly challenging. In this proposal,anthracene-containing macrocylic polyamines as new receptors for recognition and sensing of necleotides are proposed to be developed,and a new approach of combining the strong metal coordination interactions with the defined cavity size of macrocylic polyamine,and with the π-π stacking interactions between the fluorescent anthracene moiety and the nucleic base is proposed to achieve high selectivity and sensitivity.To realize this, we will synthesize a series of structurally diversified anthracene-containing macrocylic polyamine receptors with different cavity size and different functinal groups, and will systematically study these new receptors for recognition and sensing of necleotides.Through continuous rational modification of the receptor's structure, this project is expected to find out some effective receptors for nucleotides, and to uncover the possible rules of the selectivity between the cavity size of macrocylic receptors and the structure of anions of interest. Besides,this project is also expected to provide new insight on how to create effective receptors for nucleotides in aqueous solution, and to pave the way for the further related study on phosphate recognition and hydrolysis.

由于核苷酸的生物重要性，发展它们的受体分子以及对它们进行分子识别和传感具有重要的研究意义。然而，核苷酸类磷酸酯品种多样而又结构相似，同时在水相中又容易高度溶剂化，使得它们在水相中的高选择性和高灵敏度识别成为难题。本项目试图利用蒽环的荧光性能，通过结合强的金属配位作用和蒽环与核苷酸上某些碱基的π-π相互作用，同时结合大环空腔的大小调节这种新模式，来发展结构新颖的含蒽大环多胺受体分子，并实现它们对核苷酸高选择性、高灵敏度的识别和传感。为此，本项目拟制备出结构多样并具有不同空腔大小的含蒽大环多胺化合物，系统地研究它们对阴离子的识别，并通过大环结构的不断优化，找到能在水相体系中高效识别核苷酸的主体化合物，同时希望能在分子水平上揭示含蒽大环多胺与核苷酸等阴离子的识别作用规律，为解决核苷酸识别中选择性难等问题提供新的思路与方法，也为以后进一步的磷酸酯识别和水解研究打下基础。

生物体内活性物种以及环境中有害物质的检测和示踪非常重要。近年来，荧光检测的方法由于其简单方便、灵敏度高而且能够实现细胞到活体的实时检测和示踪而受到广泛关注。本项目(项目号：21472066)在国家基金委的资助下，针对一些重要的生物体内活性物种（如核苷酸，焦磷酸根，生物硫醇如半胱氨酸,硒代半胱氨酸，气体信号分子如硫化氢，活性氧化合物如次氯酸和过氧化亚硝酸根等）以及环境中有害物质（如苯硫酚，水合肼，光气等），根据其特有的化学性质及反应，发展了一系列响应快、选择性高、灵敏度好的荧光探针分子，为这些化合物的检测提供了许多新的方法。而且，这些荧光探针分子中的绝大多数可以用于活细胞和活体内的实时在线生物成像，可作为生化研究中的分子工具，具有潜在的应用价值。本项目的研究结果已经在国际SCI源刊上发表学术论文32篇，并被同行广泛引用。本项目先后培养硕士研究生10名，博士研究生2名。