Citation: Mengyu Cao, Yiyan Yin, Jingyi Qin, Jin Ouyang, Na Na. Unconventional application of a fluorescent probe for MS-based detection of multiple sulfur species in ferroptosis[J]. Chinese Chemical Letters, ;2026, 37(1): 111260. doi: 10.1016/j.cclet.2025.111260 shu

Unconventional application of a fluorescent probe for MS-based detection of multiple sulfur species in ferroptosis

Mengyu Cao ^a ,
Yiyan Yin ^a ,
Jingyi Qin ^a ,
Jin Ouyang ^b ,
Na Na ^{a, *,}

a.
Country Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China
b.
Department of Chemistry, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai 519087, China

nana@bnu.edu.cn

Received Date: 1 February 2025
Revised Date: 15 April 2025
Accepted Date: 25 April 2025
Available Online: 26 April 2025

Figures(5)

Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species (RSSs) in the thiol-dependent redox systems are crucial in ferroptosis. This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy. However, the traditional techniques, including fluorescent (FL) imaging and electrospray ionization-based mass spectrometry (MS) detection, cannot achieve the discrimination of different RSSs. Herein, simultaneous MS detection of multiple RSSs, including cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and hydrogen sulfide (H₂S), was obtained upon enhancing ionization efficiency by a fluorescent probe (NBD-O-1). Based on the interaction between NBD-O-1 and RSSs, the complex of RSSs with a fragment of NBD-O-1 can be generated, which can be easily ionized for MS detection in the negative mode. Therefore, the intracellular RSSs can be well detected upon the incubation of HeLa cells with the probe of NBD-O-1, exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection. Furthermore, the RSSs during ferroptosis in HeLa cells have been evaluated using the present strategy, demonstrating the potential for ferroptosis examinations. This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS, providing significant molecular information for addressing the ferroptosis mechanism.
- Reducing sulfur species,
- Ferroptosis,
- Fluorescent probe,
- Enhanced-ESI MS,
- Intracellular detections
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