Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe

Yameng Wang; Guantong Shen; Daniel Shiu-Hin Chan; Lei Wu; Chun-Yuen Wong; Jing Wang; Chung-Hang Leung; Wanhe Wang

doi:10.1021/acs.analchem.5c06894

Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe

Yameng Wang (Co-first Author)
, Guantong Shen (Co-first Author)
, Daniel Shiu-Hin Chan
, Lei Wu
, Chun-Yuen Wong
, Jing Wang^*
, Chung-Hang Leung^*
, Wanhe Wang^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Citations (Scopus)

Abstract

Sulfur dioxide (SO₂), a gaseous signaling molecule that can be produced endogenously in mitochondria, is an important antioxidant for maintaining redox homeostasis. Abnormal levels of mitochondrial SO₂ are associated with the pathogenesis and progression of rheumatoid arthritis (RA). Therefore, it is crucial to develop a luminescence probe that can detect subcellular SO₂ levels for unmasking the pathological changes and diagnosis of RA. However, current luminescence probes for SO₂ in RA suffer from low photostability, weak response, short emission wavelengths below 650 nm, and/or poor mitochondria targetability. In this work, we developed a near-infrared (NIR) iridium(III) complex-based probe based on the Michael addition mechanism for rapid, real-time, and accurate detection of mitochondrial SO₂. The probe not only achieved sensitive detection of SO₂ in aqueous solution with a detection limit of 2.12 μM but also imaged endogenous mitochondrial SO₂ levels in a cellular RA model. Furthermore, it visualized aspartate aminotransferase 1 (AAT1)-mediated SO₂ generation, offering insight into the mechanism of SO₂ generation in RA. Finally, it also exhibits an excellent penetration capability within 3D tumor spheroids (approximately 103 μm). Overall, this probe offers a powerful tool for effectively imaging subcellular SO₂ in RA, thereby enhancing our understanding of the pathological mechanisms of RA and accelerating the development of diagnostic tools for RA. © 2026 American Chemical Society

Original language	English
Pages (from-to)	5488-5498
Number of pages	11
Journal	Analytical Chemistry
Volume	98
Issue number	7
Online published	11 Feb 2026
DOIs	https://doi.org/10.1021/acs.analchem.5c06894
Publication status	Published - 24 Feb 2026

Funding

This work was supported by the National Natural Science Foundation of China (82402439), the Key Research and Development Program of Shaanxi (2024SF-YBXM-418), the Guangdong Basic and Applied Basic Research Foundation (2025A1515010971), the Science and Technology Development Fund, Macao SAR, China (File no. 0002/2025/NRP, 0045/2023/AMJ, 0032/2023/RIB2, 005/2023/SKL), the University of Macau, Macao SAR, China (File no. MYRGGRG2024-00202-ICMS-UMDF), and Shenzhen Science and Technology Program (File no. SGCX20250526152502004)

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@article{8d5553bce4834a77b3c189d3a256574e,

title = "Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe",

abstract = "Sulfur dioxide (SO2), a gaseous signaling molecule that can be produced endogenously in mitochondria, is an important antioxidant for maintaining redox homeostasis. Abnormal levels of mitochondrial SO2 are associated with the pathogenesis and progression of rheumatoid arthritis (RA). Therefore, it is crucial to develop a luminescence probe that can detect subcellular SO2 levels for unmasking the pathological changes and diagnosis of RA. However, current luminescence probes for SO2 in RA suffer from low photostability, weak response, short emission wavelengths below 650 nm, and/or poor mitochondria targetability. In this work, we developed a near-infrared (NIR) iridium(III) complex-based probe based on the Michael addition mechanism for rapid, real-time, and accurate detection of mitochondrial SO2. The probe not only achieved sensitive detection of SO2 in aqueous solution with a detection limit of 2.12 μM but also imaged endogenous mitochondrial SO2 levels in a cellular RA model. Furthermore, it visualized aspartate aminotransferase 1 (AAT1)-mediated SO2 generation, offering insight into the mechanism of SO2 generation in RA. Finally, it also exhibits an excellent penetration capability within 3D tumor spheroids (approximately 103 μm). Overall, this probe offers a powerful tool for effectively imaging subcellular SO2 in RA, thereby enhancing our understanding of the pathological mechanisms of RA and accelerating the development of diagnostic tools for RA. {\textcopyright} 2026 American Chemical Society",

author = "Yameng Wang and Guantong Shen and Chan, \{Daniel Shiu-Hin\} and Lei Wu and Chun-Yuen Wong and Jing Wang and Chung-Hang Leung and Wanhe Wang",

year = "2026",

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doi = "10.1021/acs.analchem.5c06894",

language = "English",

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pages = "5488--5498",

journal = "Analytical Chemistry",

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Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe. / Wang, Yameng (Co-first Author); Shen, Guantong (Co-first Author); Chan, Daniel Shiu-Hin et al.
In: Analytical Chemistry, Vol. 98, No. 7, 24.02.2026, p. 5488-5498.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe

AU - Wang, Yameng

AU - Shen, Guantong

AU - Chan, Daniel Shiu-Hin

AU - Wu, Lei

AU - Wong, Chun-Yuen

AU - Wang, Jing

AU - Leung, Chung-Hang

AU - Wang, Wanhe

PY - 2026/2/24

Y1 - 2026/2/24

N2 - Sulfur dioxide (SO2), a gaseous signaling molecule that can be produced endogenously in mitochondria, is an important antioxidant for maintaining redox homeostasis. Abnormal levels of mitochondrial SO2 are associated with the pathogenesis and progression of rheumatoid arthritis (RA). Therefore, it is crucial to develop a luminescence probe that can detect subcellular SO2 levels for unmasking the pathological changes and diagnosis of RA. However, current luminescence probes for SO2 in RA suffer from low photostability, weak response, short emission wavelengths below 650 nm, and/or poor mitochondria targetability. In this work, we developed a near-infrared (NIR) iridium(III) complex-based probe based on the Michael addition mechanism for rapid, real-time, and accurate detection of mitochondrial SO2. The probe not only achieved sensitive detection of SO2 in aqueous solution with a detection limit of 2.12 μM but also imaged endogenous mitochondrial SO2 levels in a cellular RA model. Furthermore, it visualized aspartate aminotransferase 1 (AAT1)-mediated SO2 generation, offering insight into the mechanism of SO2 generation in RA. Finally, it also exhibits an excellent penetration capability within 3D tumor spheroids (approximately 103 μm). Overall, this probe offers a powerful tool for effectively imaging subcellular SO2 in RA, thereby enhancing our understanding of the pathological mechanisms of RA and accelerating the development of diagnostic tools for RA. © 2026 American Chemical Society

AB - Sulfur dioxide (SO2), a gaseous signaling molecule that can be produced endogenously in mitochondria, is an important antioxidant for maintaining redox homeostasis. Abnormal levels of mitochondrial SO2 are associated with the pathogenesis and progression of rheumatoid arthritis (RA). Therefore, it is crucial to develop a luminescence probe that can detect subcellular SO2 levels for unmasking the pathological changes and diagnosis of RA. However, current luminescence probes for SO2 in RA suffer from low photostability, weak response, short emission wavelengths below 650 nm, and/or poor mitochondria targetability. In this work, we developed a near-infrared (NIR) iridium(III) complex-based probe based on the Michael addition mechanism for rapid, real-time, and accurate detection of mitochondrial SO2. The probe not only achieved sensitive detection of SO2 in aqueous solution with a detection limit of 2.12 μM but also imaged endogenous mitochondrial SO2 levels in a cellular RA model. Furthermore, it visualized aspartate aminotransferase 1 (AAT1)-mediated SO2 generation, offering insight into the mechanism of SO2 generation in RA. Finally, it also exhibits an excellent penetration capability within 3D tumor spheroids (approximately 103 μm). Overall, this probe offers a powerful tool for effectively imaging subcellular SO2 in RA, thereby enhancing our understanding of the pathological mechanisms of RA and accelerating the development of diagnostic tools for RA. © 2026 American Chemical Society

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DO - 10.1021/acs.analchem.5c06894

M3 - RGC 21 - Publication in refereed journal

SN - 0003-2700

VL - 98

SP - 5488

EP - 5498

JO - Analytical Chemistry

JF - Analytical Chemistry

IS - 7

ER -

Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic Iridium(III)-Based Probe

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