Breaking shackles of molecular weight and emission for NIR-II fluorophores by regulating Columb attraction interaction

The second near-infrared (NIR-II) dyes provide advantages for in vivo imaging, but challenges persist. A primary issue is the lack of practicable strategies to balance emission wavelength and molecular weight, particularly for low-molecular-weight (<500 Da) NIR-II (λ_em > 1000 nm) dyes. Here, we propose a strategy that tunes NIR-II emissions by reducing Coulomb attraction interaction, contrasting with traditional approaches that redshift absorption wavelengths through energy gap reduction. Leveraging this concept, we extend the emission wavelength of GFP chromophore-based dyes LS1-12 from the visible range into the NIR-II region, achieving a maximum emission wavelength exceeding 1200 nm with molecular weights between 226 and 449 Da. Further, the optimized NIR-II dye LS7 selectively binds Aβ₄₂ fibrils, yielding a 22.7-fold fluorescence increase in vitro and enabling real-time imaging of deposited Aβ proteins in the brains of living mice with Alzheimer's disease. This study introduces a distinct design strategy for low-molecular-weight NIR-II dyes and addresses a longstanding bottleneck in this field.