Bioinspired large Stokes shift small molecular dyes for biomedical fluorescence imaging.

Area of Science:

• Organic Chemistry
• Materials Science
• Biomedical Imaging

Background:

• Fluorescence imaging requires dyes that minimize excitation-emission overlap for improved signal-to-background ratios.
• Small molecular dyes with long Stokes shifts (>120 nm) and near-infrared (NIR) emission are scarce, limiting advanced imaging applications.

Purpose of the Study:

• To design and synthesize novel small molecular dyes with long Stokes shifts and NIR emissions.
• To evaluate the potential of these dyes for various biomedical imaging applications.

Main Methods:

• Inspired by fluorescent protein chromophores, a series of styrene oxazolone dyes (SODs) were synthesized.
• Characterization of spectral properties, including Stokes shift and NIR emission (>650 nm).
• Assessment of molecular weight (<450 Da) and functionalization with a mitochondrial targeting group (triphenylphosphonium, TPP).

Main Results:

• Synthesized SODs exhibit NIR emissions with long Stokes shifts ranging from 136 to 198 nm.
• The lead compound, SOD9, demonstrates rapid renal excretion and blood-brain barrier penetration.
• Functionalized SOD9-TPP shows promise for head-neck tumor imaging, image-guided surgery, brain neuroimaging, and pathology analysis.

Conclusions:

• Styrene oxazolone dyes represent a new class of small molecular dyes with desirable properties for fluorescence imaging.
• The developed dyes offer significant advantages in minimizing spectral cross-talk and enabling deep-tissue visualization.
• SOD9-TPP is a versatile theranostic agent for various in vivo and ex vivo imaging applications.