Constructing Stable and Wavelength‐Extended Heptamethine Cyanines via Donor Ectopic Substitution for NIR‐IIa/b Bioimaging

Organic NIR-II dyes, particularly cyanine fluorophores, offer high molar extinction coefficients, biocompatibility, and structural tunability and are popular for noninvasive, high-resolution, and -contrast in vivo imaging. However, achieving stable, long-wavelength, and large Stokes shift NIR-II cyanine suitable for NIR-IIa/IIb bioimaging is still a formidable challenge. Herein, we introduce a novel strategy that extends the emission wavelength by the enhanced Highest occupied molecular orbital (HOMO)-Lowest occupied molecular orbital (LUMO) separation through simple donor ectopic substitution at the terminal structure of NIR-II cyanine. Compared to the original NIR-II cyanine Flav7, these novel dyes (NIR-ACs) exhibited a significant emission redshift and larger Stokes shift, with the maximum emission wavelength exceeding 1300 nm (NIR-IIa) and a tail emission exceeding 1500 nm (NIR-IIb). Notably, they also demonstrate excellent stability and deeper tissue imaging ability in vivo imaging. Finally, through surface modification of nanoparticles, NIR-ACs nanoparticles (NPs) have successfully achieved high-contrast tumor and bone-targeted detecting as well as multicolor imaging, providing robust tools for in vivo diagnostics and biomedical research.