Trifluoromethyl Engineered 9-Amino-Si-Xanthene with Distinct p <i>K</i> _a and Emission Shift for Imaging Ethanol-Induced Gastric Ulcer

High-fidelity visualization of dynamic pH fluctuations in acidic and ultra-acidic microenvironments is imperative for elucidating pH-regulated pathophysiological processes. A critical challenge is the scarcity of robust near-infrared (NIR, >650 nm) fluorescent tools with tailored acidic p<i>K</i>_a, large Stokes shifts, and exceptional stability under harshly acidic conditions for high-contrast imaging. To address this, we proposed trifluoromethyl molecular engineering on 9-alkylamino-Si-xanthene by adding a trifluoromethyl tail at the terminal of the 9-alkyl chain. This subtle structural modification induced surprising photophysical transformations: significant bathochromic shifts of 35-105 nm to ∼700 nm and dramatic p<i>K</i>_a reduction from ∼8 to ∼4. The observed performance was rationalized through theoretical calculations, including HOMO-LUMO gaps, molecular electrostatic potential, natural population analysis, configuration changes, and Gibbs free energy difference. Utilizing the optimal probe <b>SiNF2</b>, we successfully observed enhanced lysosome-mitochondria communication during ferroptosis and achieved a striking 21.3-fold fluorescence contrast between cancer cells and normal cells. Notably, we demonstrate the first detection of diminished gastric acidity in an ethanol-induced gastric ulcer mouse model, highlighting the probe's potential for imaging-guided diagnosis and therapeutic monitoring of gastric disorders.