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Chemical Research in Chinese Universities ›› 2026, Vol. 42 ›› Issue (2): 547-555.doi: 10.1007/s40242-026-5307-x

• Research Articles • Previous Articles     Next Articles

Novel Naphthylamide-based Fluorescent Probe for Detecting Lipid Hydroperoxides in Ferroptosis

KONG Lingxiu1,2, LI Li1,2, ZHAO Li3, DENG Zhaohu1,2, BAO Luo1,2, QIU Xue1,2, WANG Yong1,2   

  1. 1. School of Medicine and Pharmacy, Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao 266003, P. R. China;
    2. Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, P. R. China;
    3. College of Science, China University of Petroleum (East China), Qingdao 266580, P. R. China
  • Received:2025-12-29 Accepted:2026-02-28 Published:2026-04-02
  • Contact: WANG Yong,E-mail:wangyong8866@ouc.edu.cn E-mail:wangyong8866@ouc.edu.cn
  • Supported by:
    This work was supported by the National Natural Science Foundation of China (No. 32250014), the Taishan Scholar Youth Expert Programs in Shandong Province, China (Nos. tsqn202211064 and 202103035), and the Fundamental Research Funds for the Central Universities, Ocean University of China (No. 202262015).

Abstract: Ferroptosis represents a novel form of cell death distinct from other types, characterized primarily by the accumulation of lipid peroxides (LPO) in the membrane system. The development of specific probes for detecting ferroptosis-associated LPO remains challenging. The widely recognized sensor Liperfluo, for instance, is hampered by poor photostability, underscoring the need for improved molecular tools. Herein, we developed a series of novel fluorescent probes by replacing the conventional light-sensitive perylene with a stable naphthalimide core and systematically tuning the electronic properties of the triphenylphosphine (TPP) recognition head with different substituents (—OCH3, —CF3). The optimized probe NP-1, incorporating a trifluoromethyl group, demonstrates both superior stability under ambient conditions and specific recognition of lipid hydroperoxides, yielding a robust fluorescence enhancement of >6-fold. It was revealed that the electron-withdrawing —CF3 group stabilizes the TPP moiety by lowering its electron density, thereby enhancing oxidative resistance. Furthermore, NP-1 enables to monitor RSL3-induced ferroptosis in live cells and the signal is specifically abolished by ferroptosis inhibitor. This work not only delivers a reliable sensor for detecting ferroptosis but, more importantly, establishes a general design principle by electronic modulation of the phosphorus center to develop stable and specific TPP-based probes for redox biology.

Key words: Reactive oxygen species, Lipid peroxidation, Triphenylphosphine, Photoinduced electron transfer