Synlett 2024; 35(01): 140-144
DOI: 10.1055/a-2012-0232
cluster
Functional Dyes

A Novel Heterocyclic Xanthene-Analogous pH Probe for ­Quantitative Monitoring of Cell Surface pH by Fluorescence ­Lifetime Imaging

Shuyao Wu 
a   State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. of China
,
Xinfu Zhang  ∗
a   State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. of China
,
Xiaoxi Li∗
b   Central Laboratory, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, 110042, P. R. of China
,
Shulan Sun
b   Central Laboratory, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, 110042, P. R. of China
,
Ze Hui Wang
a   State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. of China
,
Dingxuan Li
a   State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. of China
,
Yi Xiao∗
a   State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. of China
› Author AffiliationsThis work was supported by the National Natural Science Foundation of China (Nos. 21901031, 22078047, 22174009, 22278059, and 82202861), the Dalian Science and Technology Innovation Fund (No. 2020JJ25CY014), Science and Technology Foundation of Liaoning Province (2020-YQ-08 and 2022-YQ-08), and the Fundamental Research Funds for the Central Universities (Nos. DUT21YG131, DUT21YG126, DUT18RC(3)027, DUT20RC(5)024, LD202115, and DUT22LAB601).
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Abstract

Rapidly capturing slight changes in cell surface pH is extremely important to evaluate the rapid diffusion of acidic metabolites into the extracellular environment caused by disease and physiological pH fluctuations of cells. In this work, we designed a membrane-targeted pH probe, Mem-COC18 , based on a novel heterocyclic xanthene-analogous backbone. Mem-COC18 shows specific and stable staining ability towards membrane. Importantly, the fluorescence lifetime of Mem-COC18 is highly sensitive against acidity within membrane, which is in favor of quantifying pH through fluorescence lifetime imaging. Using Mem-COC18 , we recorded pH changes of 0.61 units on the surface of human cervical cancer cells (Hela) during glycolysis. Further on, we observed a robust pH-regulating mechanism of the plasma membrane that the pH fluctuation range within membrane (5.32–6.85) is much smaller than the change in extracellular environment (4.00–8.00). Consequently, we demonstrate a pH probe for quantifying small pH fluctuations within cell membrane that merits further evaluation for biology applications.

Key words

FLIM - heterocyclic xanthene-analogous - plasma membrane targeted - cell surface pH - glycolysis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2012-0232.
  • Supporting Information


Publication History

Received: 08 December 2022

Accepted after revision: 12 January 2023

Accepted Manuscript online:
12 January 2023

Article published online:
14 March 2023

© 2023. Thieme. All rights reserved

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