新型环脒基类荧光分子的设计、合成及在多肽荧光探针中的应用

Small molecule fluorescent dyes have been widely used in the fields of chemistry and biology due to their good cell permeability and slight interference to life systems. However, these fluorescent dyes still have some shortcomings in practical applications, such as acid-base sensitivity, small Stokes shift, and prone to light quenching. Since the structural modification of the current classic "core" dyes can not completely change the inherent fluorescence defect from the core skeleton, it is of great significance to design the fluorescent molecules with a novel core skeleton. According to our previous studies, the cyclic amidines have good fluorescence properties. Therefore, we try to design, synthesize novel cyclic amidines and apply them in fluorescent molecules with ipsilateral push-pull electron effects. By the rational design of the substrate, we will develop the 6π electrocyclization of N-sulfonyl triazole compounds to efficiently construct cyclic amidine fluorescent moleculars with 10π electronic structure. Systematic study of the relationship between structure and optical properties will be done to find some fluorescent molecules with enhanced properties such as pH tolerance, large Stokes shift, non-light quenching, etc. Subsequently, we’ll apply them in the synthesis of peptides fluorescent probes, which will provide material base for the visualization of biological signal transduction.

有机小分子荧光染料，因其良好的细胞渗透性和对生命系统的轻微干扰，在化学和生物学领域得到了广泛的应用。然而这些荧光染料在实际应用中仍然存在一些不足，如酸碱敏感、较小的斯托克斯位移、容易发生光淬灭等。针对经典“核心”染料的结构修饰并不能彻底改变核心骨架固有的荧光缺陷性问题，因此，开展具有新型核心骨架荧光分子的设计与合成具有重要的意义和价值。我们前期研究发现，环脒基分子具有很好的荧光特性。基于此，本项目拟以具有同侧推拉电子效应的新型环脒基类荧光分子的设计、合成及应用为目标，通过底物的合理设计，发展基于N-磺酰基三唑类化合物的6π电环化反应，用于高效构建具有10π电子结构的环脒基荧光分子骨架；系统阐述结构与光学特性的关联性，以期发现具有pH耐受、大斯托克斯位移、耐光淬灭等具有增强特性的荧光分子，并应用于多肽荧光探针的合成中，实现蛋白质的特异性标记，为生物信号转导的可视化研究提供物质基础。

有机小分子荧光染料，因其良好的细胞渗透性和对生命系统的轻微干扰，在化学和生物学领域得到了广泛的应用。然而这些荧光染料在实际应用中仍然存在一些不足，如酸碱敏感、较小的斯托克斯位移、容易发生光淬灭等。项目实施三年以来，我们针对经典“核心”染料的结构修饰并不能彻底改变核心骨架固有的荧光缺陷性问题这一挑战性的科学问题，以N-磺酰基三唑类化合物的电环化反应为基础，通过发展新的合成策略，实现快速多样化构建新型环脒基类荧光分子库，并将其应用于多肽荧光探针的合成中，实现生物学指标的示踪。. 项目执行以来，已在重要国际期刊发表高质量SCI论文10篇，其中Angew. Chem. Int. Ed. 2 篇，Chem. Sci. 1 篇，Org. Lett. 3 篇等；申请发明专利1项，授权1项；荣获广东省药理学会科技成果奖一等奖（2021）；此外通过项目的实施协助培养了3名优秀的研究生。.