Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex

Zhifeng Mao; Liuqi Ye; Fahui Hu; Xiaolei Wu; Daniel Shiu-Hin Chan; Chun-Yuen Wong; Jin-Biao Liu; Chung-Hang Leung; Wanhe Wang

doi:10.1016/j.saa.2026.127496

Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex

Zhifeng Mao (Co-first Author), Liuqi Ye (Co-first Author), Fahui Hu (Co-first Author), Xiaolei Wu, Daniel Shiu-Hin Chan, Chun-Yuen Wong, Jin-Biao Liu^*, 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

Abstract

Abnormal levels of hydrogen sulfide (H₂S) have been linked to multiple diseases, including neurological disorders, cardiovascular diseases, and cancers. Mitochondria play a central role in H₂S metabolism, and dysregulation of H₂S within mitochondria is emerging as a key factor in mitochondrial dysfunction. To explore the role of mitochondrial H₂S in live cells, a near-infrared (NIR) iridium(III) complex-based luminescence probe was constructed for the selective and sensitive detection of endogenous mitochondrial H₂S. Complex 1 exhibits a distinct luminescent response to H₂S. Upon exposure to H₂S, the nitro group in complex 1 is reduced to an amine group for triggering a 1,6-elimination reaction, resulting in luminescence quenching. The probe exhibits high-performance detection with low detection limit of 0.96 μM and exceptional specificity in aqueous buffer. Confocal imaging in living HeLa cells confirmed the probe's ability to detect both exogenous and endogenous H₂S. Additionally, the probe specifically localizes to mitochondria, enabling effective bioimaging of mitochondrial H₂S in multicellular spheroids (MCSs). Notably, this study presents the first luminescence probe for mitochondrial H₂S based on a NIR iridium(III) complex. These findings demonstrate that complex 1 is a promising tool for exploring the biological functions and pathological roles of subcellular H₂S in diseases. © 2026 Elsevier B.V.

Original language	English
Article number	127496
Number of pages	8
Journal	Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
Volume	352
Online published	21 Jan 2026
DOIs	https://doi.org/10.1016/j.saa.2026.127496
Publication status	Online published - 21 Jan 2026

Funding

This work is sponsored by, the Science and Technology Development Fund, Macao SAR, China (File no. 0002/2025/NRP, 0045/2023/AMJ, 0032/2023/RIB2, 005/2023/SKL), Guangdong Basic and Applied Basic Research Foundation (File no. 2025A1515010971), the University of Macau, Macao SAR, China (File no. MYRG-GRG2024-00202-ICMS-UMDF), Shenzhen Science and Technology Program (File no. SGCX20250526152502004).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Mao, Z., Ye, L., Hu, F., Wu, X., Chan, D. S.-H., Wong, C.-Y., Liu, J.-B., Leung, C.-H., & Wang, W. (2026). Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 352, Article 127496. Advance online publication. https://doi.org/10.1016/j.saa.2026.127496

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title = "Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex",

abstract = "Abnormal levels of hydrogen sulfide (H2S) have been linked to multiple diseases, including neurological disorders, cardiovascular diseases, and cancers. Mitochondria play a central role in H2S metabolism, and dysregulation of H2S within mitochondria is emerging as a key factor in mitochondrial dysfunction. To explore the role of mitochondrial H2S in live cells, a near-infrared (NIR) iridium(III) complex-based luminescence probe was constructed for the selective and sensitive detection of endogenous mitochondrial H2S. Complex 1 exhibits a distinct luminescent response to H2S. Upon exposure to H2S, the nitro group in complex 1 is reduced to an amine group for triggering a 1,6-elimination reaction, resulting in luminescence quenching. The probe exhibits high-performance detection with low detection limit of 0.96 μM and exceptional specificity in aqueous buffer. Confocal imaging in living HeLa cells confirmed the probe's ability to detect both exogenous and endogenous H2S. Additionally, the probe specifically localizes to mitochondria, enabling effective bioimaging of mitochondrial H2S in multicellular spheroids (MCSs). Notably, this study presents the first luminescence probe for mitochondrial H2S based on a NIR iridium(III) complex. These findings demonstrate that complex 1 is a promising tool for exploring the biological functions and pathological roles of subcellular H2S in diseases. {\textcopyright} 2026 Elsevier B.V.",

author = "Zhifeng Mao and Liuqi Ye and Fahui Hu and Xiaolei Wu and Chan, {Daniel Shiu-Hin} and Chun-Yuen Wong and Jin-Biao Liu and Chung-Hang Leung and Wanhe Wang",

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month = jan,

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doi = "10.1016/j.saa.2026.127496",

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Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex. / Mao, Zhifeng (Co-first Author); Ye, Liuqi (Co-first Author); Hu, Fahui (Co-first Author) et al.
In: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Vol. 352, 127496, 05.05.2026.

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

TY - JOUR

T1 - Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex

AU - Mao, Zhifeng

AU - Ye, Liuqi

AU - Hu, Fahui

AU - Wu, Xiaolei

AU - Chan, Daniel Shiu-Hin

AU - Wong, Chun-Yuen

AU - Liu, Jin-Biao

AU - Leung, Chung-Hang

AU - Wang, Wanhe

PY - 2026/1/21

Y1 - 2026/1/21

N2 - Abnormal levels of hydrogen sulfide (H2S) have been linked to multiple diseases, including neurological disorders, cardiovascular diseases, and cancers. Mitochondria play a central role in H2S metabolism, and dysregulation of H2S within mitochondria is emerging as a key factor in mitochondrial dysfunction. To explore the role of mitochondrial H2S in live cells, a near-infrared (NIR) iridium(III) complex-based luminescence probe was constructed for the selective and sensitive detection of endogenous mitochondrial H2S. Complex 1 exhibits a distinct luminescent response to H2S. Upon exposure to H2S, the nitro group in complex 1 is reduced to an amine group for triggering a 1,6-elimination reaction, resulting in luminescence quenching. The probe exhibits high-performance detection with low detection limit of 0.96 μM and exceptional specificity in aqueous buffer. Confocal imaging in living HeLa cells confirmed the probe's ability to detect both exogenous and endogenous H2S. Additionally, the probe specifically localizes to mitochondria, enabling effective bioimaging of mitochondrial H2S in multicellular spheroids (MCSs). Notably, this study presents the first luminescence probe for mitochondrial H2S based on a NIR iridium(III) complex. These findings demonstrate that complex 1 is a promising tool for exploring the biological functions and pathological roles of subcellular H2S in diseases. © 2026 Elsevier B.V.

AB - Abnormal levels of hydrogen sulfide (H2S) have been linked to multiple diseases, including neurological disorders, cardiovascular diseases, and cancers. Mitochondria play a central role in H2S metabolism, and dysregulation of H2S within mitochondria is emerging as a key factor in mitochondrial dysfunction. To explore the role of mitochondrial H2S in live cells, a near-infrared (NIR) iridium(III) complex-based luminescence probe was constructed for the selective and sensitive detection of endogenous mitochondrial H2S. Complex 1 exhibits a distinct luminescent response to H2S. Upon exposure to H2S, the nitro group in complex 1 is reduced to an amine group for triggering a 1,6-elimination reaction, resulting in luminescence quenching. The probe exhibits high-performance detection with low detection limit of 0.96 μM and exceptional specificity in aqueous buffer. Confocal imaging in living HeLa cells confirmed the probe's ability to detect both exogenous and endogenous H2S. Additionally, the probe specifically localizes to mitochondria, enabling effective bioimaging of mitochondrial H2S in multicellular spheroids (MCSs). Notably, this study presents the first luminescence probe for mitochondrial H2S based on a NIR iridium(III) complex. These findings demonstrate that complex 1 is a promising tool for exploring the biological functions and pathological roles of subcellular H2S in diseases. © 2026 Elsevier B.V.

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U2 - 10.1016/j.saa.2026.127496

DO - 10.1016/j.saa.2026.127496

M3 - RGC 21 - Publication in refereed journal

C2 - 41621161

SN - 1386-1425

VL - 352

JO - Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

JF - Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

M1 - 127496

ER -

Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex

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