小分子比例计量型金属离子荧光探针的设计与生物成像研究

This project aims at designing and synthesizing ratiometric two-photon fluorescent probes which can be applied to the imaging of metal ions in live cells and model animals. First, we will combine the ICT and FRET mechanisms to rationalize the fluorophores with near IR or two photon properties in order to achieve novel fluorescent metal sensors. These sensors are expected to overcome the problems such as short excitation wavelength, low penetration depth and bio-damages that are associated with current metal sensors. Afterwards, we will combine theoretical calculation with experimental results to predict and verify the spectral variations of the sensors before and after metal binding. Candidate probes will be screened and optimized. Using the candidate probes, we will fulfill the fluorescent imaging of metal ions in cells, tissue and model animals. This project will provide useful methods and tools for the investigation of the chemicak biology of biological metal ions.

本研究旨在设计合成比例计量型双光子荧光探针，实现金属离子在活细胞及模式动物中的造影。首先，我们优先选择具有红光、近红外光或者双光子性能的荧光团，结合ICT机理与FRET机理进行探针分子设计，从而获得新型金属离子荧光探针，克服目前探针分子存在的激发波长较短、成像深度浅、易造成生物损伤等问题。然后，针对不同金属离子的配位特点，设计不同的螯合基团，提高对相应金属离子的特异选择性。通过理论计算和实验密切结合，预测并验证金属离子结合前后探针分子的光谱变化，优化荧光团以及螯合团的连结方式，获得候选探针分子。利用筛选的比例计量型荧光探针对细胞、组织和活体进行荧光造影研究，实现金属离子的动态变化的定量检测。该研究将为金属离子的化学生物学研究提供重要的方法和工具。