新型双光子光敏有机基团的合成及应用

In the proposed project we plan to develop a series of novel two-photon caging groups for regulation of bioative molecules with spatiotemporal resolution. Based on known NDBF-X and NI-X skeletons, we design new types of two-photon photosensitive groups with the following principles : (1) to increase the water solubility of two-photon photosensitive compounds by adding water-soluble groups;(2) to improve the two-photon absorption cross section of two-photon photosensitive compounds by using extended conjugated systems;(3) to obtain the target two-photon photolytic compounds by use of new catalytic reactions, such as metal-catalyzed C-C, C-N cross-coupling reactions and C-H bond activation. Based on the above principles, we design and synthesize water-soluble groups with large two-photon absorption cross sections to elucidate their structure-function relationships through systematic comparison of two-photon photolytic efficiency. These results may enable us to optimize the structure of two-photoremovable protecting groups. Finally, the newly developed two-photon caged probes will be used to study the biological systems (e.g. as two-photon caged probes for biological active ions (H , Na, K, Ca or Mg) and photo-regulated cell penetrating peptides) to test their utility in vivo.

本项目拟研究发展新型双光子控制的光敏有机基团，并将其应用于生物活性探针分子的实时原位调控。具体设计在已知NDBF-X型及NI-X型双光子光敏基团的基础上，结合以下几点原则设计新型双光子光敏有机基团：（1）修饰水溶性基团增加双光子光敏化合物在生物环境下的溶解性；（2）增加共轭面以提高双光子光敏化合物的双光子吸收截面；（3）通过应用新型催化反应，如金属催化的C-C、C-N等偶联反应及C-H键活化的反应，高效率地获得目标双光子光敏探针。使用以上策略，设计、合成水溶性好、双光子吸收截面大的共轭分子骨架，通过系统比较各类衍生物的双光子光解效率，揭示它们的结构-功能关系规律，并根据这些规律优化目标分子。最后将研制得到的新型双光子光敏基团引入生物探针分子，如针对生物信号离子(H，Na，K，Ca，Mg) 以及一些生物活性肽的双光子探针，检验它们在活体生物环境中的实用价值。