基于氟硼二吡咯的镉离子双光子荧光探针的设计，合成及应用研究

Cadmium has been recognized as highly toxic heavy metal that is inessential for human beings. Efficient fluorescent probes are desired for .on-line Cd2+ detection in the cell and molecule level to define mechanisms involved in Cd2+ uptake and carcinogenesis. The development of two-photon fluorescent probe and two-photon fluorescent microscope offers powerful tools for the achievement of this target. However, there are few chromophores that are suitable as fluorophores of two-photon fluorescent probes, and even few two-photon fluorescent probes for Cd2+. This project plans to develop a series of BODIPY-based two-photon chromophores with intramolecular rigid D-π-A-π-D scaffold by introducing diphenylamine-fluorene to β position of BODIPY core. N,N-bis(pyridin-2-ylmethyl)benzenamine or polyamide, which have good selectivity and sensitivity for Cd2+, will be introduced to the chromophores. Then, substituent effect on the two-photon fluorescent property, sensing mechanism and selectivity is to be discussed, and the one with the best property will be chosen for two-photon fluorescent imaging experiments of Cd2+ in living cells. This project will provide theoretic and practical value in the exploration of BODIPY based two-photon fluorescent probe and its application in the field of two-photon Cd2+ cell imaging.

镉是一种非人体必需的具有强生物毒性的重金属元素，亟待人们发展高效的荧光探针技术，对生物细胞及组织内的镉离子进行实时在线检测，以揭示其在人体内的吸收及致病机理。双光子荧光探针及双光子荧光显微镜的出现和发展，为其提供了强有力的工具。但是，适合作为双光子荧光探针发色团的荧光基团较少，且基于镉离子的双光子荧光探针也极少报道。本项目拟通过在氟硼二吡咯（BODIPY）的β位引入二苯胺-芴（并芴）结构，合成一系列具有分子内刚性D-π-A-π-D结构的新型双光子荧光基团，并在α位引入N,N-二(2-亚甲基吡啶)苯胺或多酰胺链作为受体，进而合成一系列基于BODIPY的有机双光子荧光探针，讨论不同取代基效应对荧光探针的双光子荧光性能、识别性能及识别机理的影响，并选择性能最优者，探讨其在镉离子双光子细胞成像方面的应用，为基于BODIPY的双光子荧光探针的设计，合成及其在细胞成像领域的应用提供理论及实验依据。

具有大的双光子吸收截面的双光子荧光探针在金属离子（如镉离子）生物识别领域有着重要的应用前景。氟硼二吡咯（BODIPY）是一类性能优异的荧光发色团，但是，基于BODIPY的双光子荧光基团很少，基于BODIPY的双光子荧光探针尚未见报道。本研究主要取得以下成果：（1）合成了一系列基于BODIPY的新型双光子荧光基团，其最大双光子吸收截面可达1659 GM；（2）合成出对Cu2+具有识别性能的荧光探针，并进行性能表征；（3）在三氟乙酸钯的催化下，利用4-三氟甲磺酸酯基香豆素和吲哚化合物发生偶联反应，可以得到一种具有优异抗肿瘤活性的4-吲哚基香豆素衍生物；（4）利用路易斯酸BiCl3的催化高效的实现了吲哚化合物的二聚反应，并最终实现了2,3’-联吲哚化合物的合成；（5）在SCI收录的国际学术期刊上发表4篇SCI论文，申请专利5篇。