Versatile nitro-fluorophore as highly effective sensor for hypoxic tumor cells: design, imaging and evaluation

Area of Science:

• Organic Chemistry
• Chemical Biology
• Biomedical Imaging

Background:

• Hypoxic cells, characterized by low oxygen levels, are crucial in diseases like cancer.
• Nitroaromatic compounds can be reduced to amino groups under hypoxia.
• Developing selective sensors for hypoxic environments is vital for diagnostics and therapeutics.

Purpose of the Study:

• To design and synthesize novel hypoxic sensors based on 7H-Benzimidazole [2,1-a]benz[de]isoquinolin-7-one cores.
• To evaluate the fluorescence properties of these sensors in response to varying oxygen levels.
• To explore their potential for fluorescent imaging in hypoxic-oxic environments.

Main Methods:

• Synthesis of two series of 7H-Benzimidazole [2,1-a]benz[de]isoquinolin-7-one derivatives with nitro groups.
• Evaluation of fluorescence characteristics (enhancement or quenching) under hypoxic and normoxic conditions.
• Analysis of infrared spectra to correlate fluorescence changes with nitro-group reduction.

Main Results:

• The synthesized nitro-group containing benzimidazole derivatives displayed varied fluorescence responses.
• Partially reduced compounds showed strong fluorescence, linked to restricted nitro-group vibrations observed via infrared spectroscopy.
• Significant differences in fluorescence were detected between hypoxic and normoxic conditions.

Conclusions:

• The designed compounds function as effective hypoxic sensors with tunable fluorescence.
• Infrared spectroscopy provides insights into the mechanism of fluorescence modulation.
• These sensors offer promising capabilities for fluorescent imaging of hypoxic tissues for the first time.