A subtle structural change in a near-infrared fluorescent skeleton remolds its sensing properties for G-quadruplexes

Small-molecule near-infrared (NIR) fluorescent probes are very important in the field of G-quadruplexes (G4s, higher-order nucleic acid structures adopted by guanine-rich sequences), which would help understand the folding dynamics and the cellular consequences of G4s. However, the NIR probes that enable real-time visualization of G4 structures in live cells are rather limited. In this study, by a subtle structural change in a NIR fluorescent skeleton, we succeeded in developing a promising NIR probe named VIN-2 for detecting G4s in both cell-free and cell-based systems. VIN-2 was proved to bind at the terminal guanine tetrads (G-quartets), and emit significant fluorescence possibly because of the lock of its molecular rotations. Moreover, VIN-2 had the potential to be used in monitoring mitochondrial G4 folding dynamics in real time. This study may provide an effective chemical tool for exploring the functions of G4s in mitochondria.