Carbonothioate-Triggered Cascade Cyclization Enables High-Specificity Fluorescence Imaging of Hydrogen Polysulfides

Area of Science:

• Chemical Biology
• Molecular Imaging
• Redox Signaling

Background:

• Hydrogen polysulfides (H₂Sn) are vital redox signaling molecules with poorly understood mechanisms.
• Existing fluorescent probes for H₂Sn often suffer from interference by biothiols and hydrogen sulfide (H₂S).
• Reliable detection methods are crucial for elucidating the biological roles of H₂Sn.

Purpose of the Study:

• To develop a novel fluorescent probe for the specific and sensitive detection of hydrogen polysulfides (H₂Sn).
• To overcome limitations of existing probes, particularly interference from other sulfur species.
• To visualize endogenous H₂Sn dynamics in biological systems, including disease models.

Main Methods:

• Design and synthesis of a carbonothioate-based trigger utilizing a cascade cyclization reaction.
• Preparation and evaluation of eight new fluorescent probes (CTP 1-8).
• Testing probe selectivity against biothiols and H₂S, and application in fluorescence imaging of H₂Sn in living cells and mice.

Main Results:

• Developed eight novel carbonothioate-based fluorescent probes (CTP 1-8) for H₂Sn detection.
• CTP-8 demonstrated high sensitivity and selectivity for H₂Sn, with minimal interference.
• Successfully visualized endogenous H₂Sn fluctuations in insulin-resistant cells and type 2 diabetes mellitus (T2DM) mice using CTP-8.

Conclusions:

• A unique carbonothioate-based trigger enables specific and sensitive detection of H₂Sn.
• CTP-8 serves as a powerful tool for real-time imaging of H₂Sn dynamics in biological contexts, including T2DM.
• The developed strategy offers a versatile platform for future fluorescent probe development targeting H₂Sn biology.