Less Is More: Donor Engineering of a Stable Molecular Dye for Bioimaging in the NIR-IIb Window

Fluorescence molecular imaging aims to enhance clarity in the region of interest, particularly in the near-infrared IIb window (NIR-IIb, 1500-1700 nm). To achieve this, we developed a novel small-molecule dye, named DA-5, based on classic cyanine dyes (heptamethine or pentamethine is essential for wavelengths beyond 1000 nm). By reducing excessive polymethine to a single methine and disrupting symmetry to form an asymmetric donor-π-acceptor (D-π-A) architecture, we enhanced the donor's electron-donating capability, yielding emission at 1088 nm. DA-5 exhibits superior properties, including excellent chemo- and photostability, resistance against solvatochromism-caused quenching, and antiaggregation in aqueous solution. With a large Stokes shift (241 nm) and high brightness (321 M^-1 cm^-1), DA-5 enables high-performance imaging of the lymphatic system, intestinal vessels, whole-body angiography, and cerebral and hindlimb microvasculature in NIR-IIb. This molecular design strategy offers a promising platform for advancing in vivo biophotonics.