Excited-State Conjugation/De-Conjugation Driven Nonradiative Thermal Deactivation for Developing Fluorogenic Probes...

Fluorogenic probes have shown great potential in imaging biological species as well as in diagnosing diseases, especially cancers. However, the fluorogenic mechanisms are largely limited to a few photophysical processes to date, typically including photoinduced electron transfer (PeT), fluorescence resonant energy transfer (FRET), and intramolecular charge transfer (ICT). Herein, by calculations and experiments, we set forth that the inhibition of the excited-state π-conjugation in meso-ester Si-rhodamine SiR-COOM or the de-π-conjugation in meso-ester cyanine 5 Cy5-COOM via the "ester-to-carboxylate" conversion can operate as a general fluorogenic mechanism to fabricate fluorogenic probes. Based on the mechanism and considering the higher chemical stability of Cy5-COOM than that of SiR-COOM, we developed, as a proof-of-concept, three fluorogenic probes Cy5-APN, Cy5-GGT, and Cy5-NTR on the basis of the Cy5-COOM platform for sensing cancer biomarkers aminopeptidase N (APN), γ-glutamyltranspeptidase (GGT), and nitroreductase (NTR), respectively, and demonstrated their outstanding performances in distinguishing between cancerous and normal tissues with the high tumor-to-normal tissue ratios in the range of 9-14.