Chlorination-induced pK_a decrease: an improved strategy to design ratiometric hypochlorite fluorescent probes with...

Area of Science:

• Analytical Chemistry
• Biomedical Imaging
• Chemical Biology

Background:

• Hypochlorite (ClO⁻) is a crucial reactive oxygen species involved in various physiological and pathological processes.
• Developing selective and sensitive probes for ClO⁻ detection is essential for biological research and disease diagnosis.
• Existing probes often suffer from low selectivity or complex detection mechanisms.

Purpose of the Study:

• To design and synthesize a novel ratiometric fluorescent probe for selective detection of hypochlorite (ClO⁻).
• To investigate the probe's performance in terms of sensitivity, selectivity, and response mechanism.
• To demonstrate the probe's utility for imaging intracellular ClO⁻ and studying disease models.

Main Methods:

• A new strategy based on ClO⁻-triggered chlorination and pKa decrease of phenols was employed.
• Synthesis and characterization of the ratiometric fluorescent probe Naph-DFOB.
• In vitro and in vivo fluorescence imaging experiments using two-photon excitation.
• Application of the probe in a lipopolysaccharide (LPS)-induced acute lung injury mouse model.

Main Results:

• The developed probe Naph-DFOB exhibited a ratiometric fluorescence change (509 nm to 628 nm) in response to ClO⁻.
• The probe demonstrated high sensitivity and selectivity for ClO⁻ detection.
• Intracellular ClO⁻ in living cells was successfully imaged using two-photon excitation.
• Naph-DFOB proved effective in investigating LPS-induced acute lung injury in a mouse model.

Conclusions:

• A novel, highly selective, and sensitive two-photon ratiometric fluorescent probe (Naph-DFOB) for ClO⁻ detection was successfully developed.
• The probe's mechanism relies on ClO⁻-triggered chlorination and pKa-dependent fluorescence.
• Naph-DFOB is a valuable tool for real-time imaging of intracellular ClO⁻ and studying related biological processes and diseases.