Cysteine ratiometric fluorescence sensing reaction actuated B-ring naphthalene-substituted flavonol-based PhotoCORM: precisely controlled linear CO liberation

Abstract

The first B-ring-naphthalene-substituted flavonol-based ratiometric fluorescent cysteine (Cys) probe NCA (2-(naphthalen-2-yl)-4-oxo-4H-chromen-3-yl acrylate) was developed, which also acts as a precursor of the photoCORM. NCA enables fast (20 s), highly selective and sensitive (limit of detection: 23 nM) detection and visualization of exogenous and endogenous Cys in live HeLa cells and zebrafish. The fluorophore HNC (3-hydroxy-2-(naphthalen-2-yl)-4H-chromen-4-one), driven and quantitatively produced by the Cys sensing reaction, was designed as a photoCORM. By controlling the light illumination intensity or duration or photoCORM dosage, HNC can supply accurate and quantitatively controlled linear CO gas in an aerobic environment. The location and CO releasing procedure of HNC can be monitored in real time by its own fluorescence. NCA and all its reaction products are biocompatible. Our study presents the first B-ring-naphthalene-substituted flavonol-based ratiometric fluorescent probe to efficiently detect and image exogenous and endogenous Cys both in vitro and in vivo, which also acts as a Cys-driven and visible-light triggerable photoCORM precursor, for linear CO delivery in an aerobic environment. This study not only has promising applications in Cys sensing, imaging and spatiotemporal control of CO liberation in live systems, but will also contribute to the development of handy molecular tools for CO gas therapy and clinical diagnosis.