One-electron reduction triggered nitric oxide release for ischemia-reperfusion protection

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Materials Science

Background:

• Nitric oxide donors (NODs) are crucial in biological research and treating cardiovascular diseases.
• Current NODs often rely on thiols for nitric oxide (NO) release, presenting complex mechanisms and potential resistance.
• There is a need for novel NODs with alternative activation pathways for broader therapeutic applications.

Purpose of the Study:

• To develop a new class of NODs activated by one-electron reduction.
• To create a system where NO release is coupled with a fluorescent signal for monitoring.
• To evaluate the biocompatibility and therapeutic potential of these novel NODs in cellular models.

Main Methods:

• Synthesis of N-nitrosated electron-deficient dyes as novel NODs.
• Electrochemical and spectral studies to characterize NO release mechanism and efficiency.
• In vitro cell-based assays using endothelial cells in oxygen and glucose deprivation (OGD) models.

Main Results:

• N-nitrosated electron-deficient dyes demonstrated NO release upon one-electron reduction.
• A simultaneous fluorophore generation allowed real-time monitoring of NO release profiles.
• NOD f3 exhibited good biocompatibility and high reduction efficiency.
• Demonstrated cell-protective effects in endothelial cells under OGD conditions.

Conclusions:

• N-nitrosated electron-deficient dyes represent a new strategy for designing reduction-triggered NODs.
• This approach offers a controllable and monitorable method for NO delivery.
• These novel NODs show promise for therapeutic interventions in ischemia-reperfusion injuries and related diseases.