Citation: Zhiyuan Qi, Jing Chen, Wenhao Xie, Zhibei Qu, Motonari Uesugi, Lu Zhou. Thiophosphoryl pyridinol/pyrimidinol-based probes for covalent and fluorescent sensing of intracellular Cu²⁺[J]. Chinese Chemical Letters, ;2026, 37(9): 111924. doi: 10.1016/j.cclet.2025.111924 shu

Thiophosphoryl pyridinol/pyrimidinol-based probes for covalent and fluorescent sensing of intracellular Cu²⁺

Zhiyuan Qi ^{a, 1} ,
Jing Chen ^{a, 1} ,
Wenhao Xie ^{a, 1} ,
Zhibei Qu ^a ,
Motonari Uesugi ^{a, b, *,} ,
Lu Zhou ^{a, c, *,}

a.
School of Pharmacy, Fudan University, Shanghai 201203, China
b.
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
c.
Quzhou Fudan Institute, Quzhou 324002, China

uesugi@scl.kyoto-u.ac.jp

zhoulu@fudan.edu.cn

Received Date: 22 June 2025
Revised Date: 28 September 2025
Accepted Date: 29 September 2025
Available Online: 29 September 2025

Figures(5)

Copper (Cu) is essential for life, with its redox cycling (Cu⁺/Cu²⁺) underpinning key biological processes. Although significant progress has been made in developing fluorescent probes for Cu⁺, reliable tools for detecting intracellular Cu²⁺ remain limited, leaving a critical gap in the bioinorganic chemistry toolkit. To address this need, we developed an activity-based sensing (ABS) strategy for live-cell Cu²⁺ detection that leverages Cu²⁺-dependent bioorthogonal conjugation. Specifically, we engineered thiophosphoryl pyridinol/pyrimidinol dyes that undergo Cu²⁺-mediated activation, enabling covalent labeling of proximal proteins within intracellular Cu²⁺-enriched microdomains and concomitant turn-on fluorescence. This work not only offers a powerful tool for detecting intracellular Cu²⁺ fluctuations under exogenous stimuli but also proposes thiophosphorylated pyridinol/pyrimidinol scaffolds as a versatile platform for future intracellular Cu²⁺ sensing applications.
- Thiophosphorylated pyridinol/pyrimidinol,
- Activity-based sensing,
- Intracellular Cu²⁺,
- Probes,
- Fluorescence imaging
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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Thiophosphoryl pyridinol/pyrimidinol-based probes for covalent and fluorescent sensing of intracellular Cu2+

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通讯作者: 陈斌, bchen63@163.com

Thiophosphoryl pyridinol/pyrimidinol-based probes for covalent and fluorescent sensing of intracellular Cu²⁺