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

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

扫码查看
原文链接
  • 万方数据
  • 维普
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 flu-orescent properties in intracellular microenvironment are unclear.Here,a Cu(Ⅱ)-catalyzed cascade cou-pling 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 pH stability and large Stokes shift.Impor-tantly,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 ze-brafish.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.

Fluorescent sensorBenzo[4,5]imidazo[1,2-a]pyrimidineLysosomeViscosityLysosomal storage disordersStructure-inherent targetingFluorescence imaging

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

展开 >

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

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

The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China

2024

10.1016/j.cclet.2024.110050

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(11)