Design, Synthesis,and <i>In Vivo</i> Imagingof a Stable Xanthene-Based Dye with NIR-II Emission up to 1450 nm

The development of long-wavelength near-infrared II (NIR-II, 900–1700 nm) dyes is highly desirable but challenging. To achieve both red-shifted absorption/emission and superior <i>in vivo</i> imaging capabilities, a donor–acceptor–donor (D–A–D) xanthene core was strategically modified by extending π-conjugated double bonds and enhancing electron-donating properties. Two dyes named <b>VIX-1250</b> and <b>VIX-1450</b> were synthesized and exhibited notably red-shifted absorption/emission peaks at 942/1250 and 1098/1450 nm, respectively. Among them, <b>VIX-1450</b> demonstrated superior chemo- and photostability even at such long wavelengths. Fluorescent angiography using <b>VIX-1450</b> micelles enabled high-clarity blood vessel imaging with a remarkable signal-to-noise ratio (SNR), underscoring that the dye’s large Stokes shift (352 nm), good brightness (13 M^–1 cm^–1), and long wavelength served as key factors for high-quality <i>in vivo</i> biosensing. Additionally, <b>VIX-1450</b> combined with <b>ICG</b> for dual-color imaging achieved near-zero optical cross talk, enabling different organ labeling. This study provides a new direction for the design of long-wavelength organic dyes.