Germanium‐Based Long‐Conjugation Xanthene Fluorophores for Bioimaging in Optimal NIR‐II Sub‐Window

ABSTRACT The near‐infrared‐IIx (NIR‐IIx, 1400–1500 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 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 h under harsh oxidative and reductive conditions. In vivo studies confirm 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, EGe5‐PEG 45 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.