Design strategies for fluorene-skeleton near-infrared small-molecule dyes and their NIR-II imaging applications

Long-wavelength near-infrared small-molecule dyes hold enormous application potential in the field of biophotonics. Traditional strategies achieve red-shifted wavelengths by expanding aromatic structures, but often sacrifice application performances such as photostability, cell permeability, and functionality. Given the limitations of aromatic structures, this study turns to ground-state antiaromaticity to explore a new approach: by substituting the nitrogen-containing groups at the 3,6-positions and the phenyl group at the 9-position of the fluorene skeleton, the intramolecular electron push-pull effect is enhanced, aiming to optimize the comprehensive performance of near-infrared dyes by inhibiting the twisted intramolecular charge transfer (TICT) effect. Comparison with traditional rhodamine dyes shows that the fluorene dye skeleton exhibits excellent structural stability; even after introducing electron-withdrawing substituents that inhibit TICT at its 3,6-positions for group modification, its photophysical properties can still remain stable, this result further confirms that the fluorescence quantum yield of fluorene-skeleton dyes is not regulated by the TICT effect. This design successfully improves the water solubility of fluorene skeleton dyes, and SAF-1 and SAF-2 still show excellent second near-infrared window imaging capabilities. We used the amphiphilic material DSPE-PEG2000 to encapsulate them, among which DSPE-PEG2000-FA@SAF-1 successfully achieved imaging of mouse tumor tissues. The above results indicate that ground-state antiaromaticity is an effective strategy for the development of long-wavelength dyes.