Single-Benzene-Based Clickable Fluorophores for In Vitro and In Vivo Bioimaging

Area of Science:

• Organic chemistry
• Photophysics
• Biomedical imaging

Background:

• Development of novel fluorophores is crucial for advancing bioimaging techniques.
• Miniaturized, single-benzene-based fluorophores offer potential advantages in terms of synthesis and application.
• Tetrafluoroterephthalonitrile serves as a versatile precursor for synthesizing functional organic molecules.

Purpose of the Study:

• To report a series of miniaturized, clickable single-benzene-based fluorophores.
• To investigate the structure-property relationships of these fluorophores, focusing on photophysical characteristics.
• To demonstrate the utility of these novel fluorophores in bioimaging applications.

Main Methods:

• Synthesis of fluorophores derived from tetrafluoroterephthalonitrile.
• Characterization of photophysical properties, including absorption and emission spectra.
• Protein conjugation of the synthesized fluorophores.
• Evaluation of fluorophore performance in in vitro and in vivo bioimaging models.

Main Results:

• A series of miniaturized, clickable single-benzene-based fluorophores were successfully synthesized.
• Fluorophores featuring a tetrahydroquinoxaline skeleton displayed improved photophysical properties compared to those with a dihydro[1,4]thiazine skeleton.
• Enhanced electron delocalization in the tetrahydroquinoxaline derivatives contributed to their superior performance.
• The synthesized clickable fluorophores were effectively applied in both in vitro and in vivo bioimaging after protein conjugation.

Conclusions:

• Miniaturized, single-benzene-based fluorophores derived from tetrafluoroterephthalonitrile represent a promising class of imaging agents.
• The tetrahydroquinoxaline scaffold offers a viable strategy for enhancing fluorophore photophysical properties.
• These easily synthesized and clickable fluorophores are suitable for protein-based bioimaging, facilitating diverse biological studies.