Construction of a fluorine substituted chromenylium-cyanine near-infrared fluorophore for ratiometric sensing

Near-infrared (NIR) fluorescent probes have been considered as powerful tools for exploring bioactive species and biological processes in living systems by virtue of the substantial merits of the NIR window (such as minimal photo-toxicity, deep tissue penetration, and low background interference). However, the development of effective NIR fluorescent probes for biological application is still facing great challenges due to some weakness (for example, pH sensitivity, poor chemical and photo-stability) of mainly current NIR fluorophores. Herein, we synthesized a novel fluorine atom substituted NIR chromenylium-cyanine fluorophore, termed CCF-OH, with an optically tunable hydroxyl group. Compound CCF-OH possess several optical advantages, including high chemical stability, high photo-stability, and high fluorescence quantum yield (Phi = 0.47). Significantly, a low pK(a) value (6.3) of CCF-OH was obtained, making its fluorescence signal steady around the pH ranging from 6.8 to 8.1. To demonstrate the practicability of CCF-OH, a mitochondria-targeted near-infrared fluorescent probe, N-Cys, was developed by masking the hydroxyl group of CCF-OH with an acrylate group as the recognition unit for cysteine (Cys). N-Cys responded to Cys with an obvious ratiometric signal. Furthermore, N-Cys has also been successfully applied for ratiometric NIR imaging of Cys in living cells, suggesting the great potential of the new NIR fluorophore, CCF-OH, for practical applications in living systems. (c) 2017 Elsevier B.V. All rights reserved.