Imidazole-fused benzothiadiazole-based red-emissive fluorescence probe for lysosomal pH imaging in living cells

Lingling Li; Yang Li; Yijing Dang; Tingting Chen; Ao Zhang; Chunyong Ding; Zhiai Xu

doi:10.1016/j.talanta.2020.121066

Imidazole-fused benzothiadiazole-based red-emissive fluorescence probe for lysosomal pH imaging in living cells

Talanta. 2020 Sep 1:217:121066. doi: 10.1016/j.talanta.2020.121066. Epub 2020 Apr 28.

Authors

Lingling Li¹, Yang Li², Yijing Dang¹, Tingting Chen², Ao Zhang³, Chunyong Ding⁴, Zhiai Xu⁵

Affiliations

¹ School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.
² CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
³ School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
⁴ School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: [email protected].
⁵ School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China. Electronic address: [email protected].

PMID: 32498855
DOI: 10.1016/j.talanta.2020.121066

Abstract

Intracellular pH is a key physiological factor for controlling the activities and functions of cells and lysosome is a vital subcellular organelle. Thus, developing a novel lysosome-targeting fluorescence probe for selective and sensitive detection of lysosomal pH in living cells is very important. In this work, we synthesized a series of fluorescence probes based on imidazole-fused benzothiadiazole. The optical properties of these probes were easily adjusted by modifying the substituents with different electron-withdrawing/donating ability in imidazole moiety. All of them showed acid-response and decreased fluorescence intensity during pH values changing from 4.0 to 8.5. The introduction of morpholine group allowed them to specifically respond to the changes of lysosomal pH. Among them, probe MIBTAA possessed a suitable pK_a value (5.3) and showed good linear response to pH (R² = 0.9918) with red emission when pH changed from 4.4 to 5.6. The probe was successfully applied for monitoring pH variation in living cells induced by proton-pump inhibitor Baf-A1 and chloroquine, indicating its great potential for pH imaging in biological applications.

Keywords: Fluorescence probe; Imidazole-fused benzothiadiazole; Lysosome; pH imaging.

MeSH terms

Fluorescent Dyes / chemical synthesis
Fluorescent Dyes / chemistry*
Humans
Hydrogen-Ion Concentration
Imidazoles / chemistry*
Lysosomes / chemistry
MCF-7 Cells
Molecular Structure
Optical Imaging*
Spectrometry, Fluorescence
Thiadiazoles / chemistry*
Tumor Cells, Cultured

Substances

Fluorescent Dyes
Imidazoles
Thiadiazoles
benzo-1,2,3-thiadiazole
imidazole