Benzo[4,5]imidazo[1,2-a]pyrimidine-based structure-inherent targeting fluorescent sensor for imaging lysosomal viscosity and diagnosis of lysosomal storage disorders  

作　　者：Jiao Chen Zihan Zhang Guojin Sun Yudi Cheng Aihua Wu Zefan Wang Wenwen Jiang Fulin Chen Xiuying Xie Jianli Li 

机构地区：[1]Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education,Xi'an Key Laboratory of Functional Supramolecular Structure and Materials,College of Chemistry&Materials Science,Northwest University,Xi'an 710127,China [2]Key Laboratory of Resource Biology and Biotechnology in Western China,Ministry of Education,Biomedicine Key Laboratory of Shaanxi Province,Lab of Tissue Engineering,the College of Life Sciences,Faculty of Life Science&Medicine,Northwest University,Xi'an 710069,China [3]The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China

出　　处：《Chinese Chemical Letters》2024年第11期454-460,共7页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.22077099,22171223 and 22307102);the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32);the Technology Innovation Leading Program of Shaanxi(Nos.2023KXJ-209 and 2024QCY-KXJ-142);the Key Research and Development Program of Shaanxi(No.2024GHZDXM-22);the Natural Science Basic Research Program of Shaanxi(Nos.2023-JC-YB-141 and 2022JQ-151);Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206);the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080);the Yan’an City Science and Technology Project(No.2022SLZDCY-002)。

摘　　要：Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.

关 键 词：Fluorescent sensor Benzo[4 5]imidazo[1 2-a]pyrimidine Lysosome VISCOSITY Lysosomal storage disorders Structure-inherent targeting Fluorescence imaging 

分 类 号：R313[医药卫生—基础医学] O626[理学—有机化学] TP212[理学—化学]