Chemiluminescent Probes for Imaging H₂S in Living Animals

Area of Science:

• Biochemistry
• Chemical Biology
• Analytical Chemistry

Background:

• Hydrogen sulfide (H2S) is a crucial endogenous signaling molecule involved in various physiological and pathological processes.
• Accurate and sensitive detection of H2S in biological systems is essential but technically challenging.

Purpose of the Study:

• To develop and characterize novel chemiluminescent probes for the precise measurement of H2S in living cells and animals.
• To establish a predictive model for designing improved chemiluminescent probes based on chemical structure analysis.

Main Methods:

• Total chemical synthesis and characterization of three 1,2-dioxetane chemiluminescent probes (CHS-1, CHS-2, CHS-3).
• Evaluation of probe performance including light emission kinetics, selectivity against reactive species, and detection limits.
• Application of the CHS-3 probe for cellular H2S detection using a multi-well plate reader and in vivo imaging of H2S in live mice.

Main Results:

• Successful synthesis and characterization of CHS-1, CHS-2, and CHS-3 probes.
• Probes exhibit instantaneous light emission upon reaction with H2S at physiological pH, with sustained signal for over an hour.
• High selectivity of the probes against other reactive sulfur, oxygen, and nitrogen species was confirmed.
• A predictive model for designing chemiluminescent probes was developed based on electronic properties.
• CHS-3 probe successfully detected cellular H2S and enabled in vivo imaging of H2S in live mice.

Conclusions:

• The developed CHS probes offer a sensitive and selective method for detecting H2S in biological contexts.
• The predictive model aids in the rational design of next-generation chemiluminescent H2S sensors.
• These probes represent a significant advancement for studying the biological roles of H2S in health and disease.