Theoretical Design of H ₂ S Fluorescent Probes Based on π Expansion and a Strong Electron‐Withdrawing Group

Hydrogen sulfide (H 2 S) regulates crucial physiological and pathological processes, and its dysregulation is linked to serious diseases. A sensitive and selective imaging method is essential for detecting endogenous H 2 S in complex biological systems. The probe benzo1‐DCM‐O‐NBD and its product benzo1‐DCM‐OH, derived from π expansion of the DCM‐O‐NBD probe, have been studied for their luminescence mechanisms. Investigations into the effects of various geometric modifications on their optical properties have been conducted. Results of calculation reveal that the introduction of strong electron‐withdrawing substituent groups (F, Cl, Br, and CN) into the benzopyran position of benzo1‐DCM‐OH effectively suppresses molecular skeleton scissoring vibrations and significant geometric relaxations associated with line‐type π expansion, thereby enhancing fluorescence emission. This approach also enhances two‐photon absorption (TPA) ability and spectral resolution. CN‐benzo1‐DCM‐OH particularly exhibits excellent two‐photon fluorescence properties. These studies have led to the identification of potential materials for biological imaging and H 2 S detection that provide easily distinguishable spectra (with a Stokes shift of up to 85.43 nm), improved luminous efficiency (14.1%), and a larger effective TPA cross section (295 GM at 950 nm). This research provides a more detailed theoretical framework for the design of novel two‐photon excited fluorescent probes.