Germanium-based long-conjugation xanthene fluorophores for bioimaging in optimal NIR-II sub-window

Abstract The near-infrared-IIx (NIR-IIx, 1,400-1,500 nm) sub-window theoretically surpasses the conventional near-infrared-II (NIR-II) region in optical imaging fidelity but requires luminophores with high brightness and stability. Herein, we present a germanium-engineered xanthene fluorophore (EGe5) featuring extended π-conjugation and a planarized pentagonal core, as unequivocally resolved by single-crystal X-ray analysis. The vertically aligned methyl groups sterically hinder molecular vibration, while germanium's heavy-atom effect enhances radiative decay, collectively resulting in a 3.3% quantum yield in the NIR-II window and high NIR-IIx brightness. In addition, EGe5 retains nearly unchanged fluorescence intensity for over 12 hours under harsh oxidative and reductive conditions. In vivo studies confirms its prolonged circulation time (> 60 min) is enough for persistent NIR-IIx fluorescent angiography, which helps to identify the intestinal obstruction by tracing the diseased intestinal wall blood vessels. Furthermore, PEGylated EGe5 (EGe5-PEG45) achieves rapid renal clearance and enables high-contrast excretory urography, dynamically tracking hydronephrosis progression in ureteral obstruction models. This work provides a molecular design paradigm for NIR-IIx probes and a versatile tool for minimally invasive diagnosis of gastrointestinal/urological diseases.