Structure-Function Analysis of Hydroxy-1,8-Naphthalimide Photoacids for ESPT-Driven H₂S Probes

Area of Science:

• Organic Chemistry
• Analytical Chemistry
• Biochemistry

Background:

• Hydroxy-1,8-naphthalimides are photoacidic fluorophores enabling excited-state proton transfer (ESPT).
• ESPT leads to red-shifted fluorescence, useful for developing sensitive detection probes.
• Hydrogen sulfide (H2S) is a crucial signaling molecule with implications in various biological processes.

Purpose of the Study:

• To synthesize and evaluate novel reaction-based fluorescent probes for selective H2S detection.
• To investigate the structure-activity relationships of hydroxy-1,8-naphthalimide derivatives for H2S sensing.
• To explore the role of hydroxyl substituent position in modulating probe performance.

Main Methods:

• Synthesis of four hydroxy-1,8-naphthalimide-based fluorescent probes (L1-L4).
• Evaluation of probe photophysical properties, including fluorescence emission and ESPT efficiency.
• Assessment of probe reactivity and selectivity towards H2S and other biologically relevant thiols.

Main Results:

• Probe sensitivity and emission wavelength were significantly influenced by the hydroxyl group's position.
• L1 (3-hydroxy) and L3 (4-hydroxy) probes showed distinct fluorescence maxima (617 nm and 550 nm) and rapid H2S reactivity.
• L3 exhibited enhanced sensitivity due to a more stable naphtholate intermediate; L4 demonstrated high selectivity for H2S over other thiols.

Conclusions:

• Key structure-activity relationships for naphthalimide-based H2S probes were established.
• The position of the hydroxyl group is critical for optimizing ESPT, emission, and sensitivity.
• These findings provide design strategies for developing advanced fluorescent probes for reactive sulfur species detection.