Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes That Enable Endogenous...

Area of Science:

• Organometallic Chemistry
• Chemical Biology
• Neuroscience

Background:

• Carbon monoxide (CO) is an important gasotransmitter with therapeutic potential, but studying its biological roles is difficult due to limited visualization tools.
• Existing methods struggle to track the transient and freely diffusing CO molecule in complex biological environments.

Purpose of the Study:

• To develop novel tools for the direct visualization and detection of carbon monoxide in living systems.
• To establish structure-activity relationships for palladium-based probes to enable selective CO detection.

Main Methods:

• Designed and synthesized a series of activity-based sensing (ABS) probes utilizing palladium-mediated carbonylation chemistry.
• Systematically altered the palladium-ligand environment (sp3-S, sp3-N, sp2-N) to establish structure-activity relationships.
• Optimized probe (COP-3E-Py) for imaging CO release in live cells and brain tissue.

Main Results:

• Developed an optimized CO probe (COP-3E-Py) with selective reactivity under physiological conditions.
• Demonstrated successful imaging of CO release in live cells and fly brains.
• Monitored endogenous CO production linked to presynaptic dopamine release in fly brains.

Conclusions:

• The developed ABS probe provides a unique tool for studying carbon monoxide in living systems.
• This work highlights the utility of synthetic methods and organometallic chemistry for activity-based sensing.
• The findings facilitate further research into the biological functions and therapeutic applications of CO.