Dihydroxanthene‐Derived Dioxetane Chemiluminophores for Activatable in Vivo Imaging

A new family of dihydroxanthene-derived dioxetane chemiluminophores (DhX-CLs) is developed through rational design, structural optimization, and acceptor engineering. DhX-CLs feature a novel modular core structure, tunable chemiluminescence wavelengths, high quantum yields, long near-infrared emission, biocompatibility, activatable capability, and in vivo imaging applicability.

Abstract

Chemiluminophores with optimal chemiluminescence properties and versatile structures adaptable into activatable chemiluminescent probes are of particular interest for biosensing and imaging owing to their high sensitivity and signal-to-noise ratio. However, such chemiluminophores are still limited. Herein, we report dihydroxanthene-derived chemiluminophores (DhX-CLs) that integrate an adamantyl-dioxetane moiety with a rationally designed dihydroxanthene-like core skeleton featuring an extended and restricted π-electron system. Structural optimization of the dihydroxanthene-aldehyde-based prototype chemiluminophore generated a bright yellow chemiluminophore DhX-CL4 with a quantum yield of 35.4% under aqueous conditions, higher than those of existing dioxetanes in the green-to-near-infrared (NIR) range beyond 500 nm. Further π-electron extension and acceptor engineering resulted in NIR chemiluminophores with high brightness and biocompatibility. Notably, DhX-CL7 exhibits long-lasting chemiluminescence with a maximum NIR emission at 808 nm and a quantum yield 3.17%, higher than those of most reported NIR chemiluminophores. We further demonstrated that caging of these chemiluminophores with analyte-responsive moieties afforded activatable chemiluminescent probes for in vivo imaging of β-galactosidase and peroxynitrite. Overall, this new family of chemiluminophores, with tunable emission wavelengths and remarkable chemiluminescence properties, serves as a versatile platform for in vivo chemiluminescence imaging.

Zum Volltext