Design and Synthesis of RhodIndolizine Dyes with Improved Stability and Shortwave Infrared Emission up to 1250 nm

The design of shortwave infrared (SWIR) emissive small molecules with good stability in water remains an important challenge for fluorescence biological imaging applications. A series of four SWIR emissive rhodindolizine (RI) dyes were rationally designed and synthesized to probe the effects of nonconjugated substituents, conjugated donor groups, and nanoencapsulation in a water-soluble polymer on the stability and optical properties of the dyes. Steric protecting groups were added at the site of a significant LUMO presence to probe the effects on stability. Indolizine donor groups with added dimethylaniline groups were added to reduce the electrophilicity of the dyes toward nucleophiles such as water. All of the dyes were found to absorb (920-1096 nm peak values) and emit (1082-1256 nm peak values) within the SWIR region. Among xanthene-based emissive dyes, emission values >1200 nm are exceptional with 1256 nm peak emission being a longer emission than the recent record setting VIX-4 xanthene-based dye. Half-lives were improved from ∼5 to >24 h through the incorporation of either steric-based core protection groups or donors with increased donation strength. Importantly, the nanoencapsulation of the dyes in a water-soluble surfactant (Triton-X) allows for the use of these dyes in biological imaging applications.