Carbazole-based fluorescent probes for G-quadruplex DNA targeting with superior selectivity and low cytotoxicity

[Display omitted] •A class of carbazole-based fluorescent“OFF-ON” probes for the detection of G-quadruplex DNA was successfully established.•Compared with ssDNA and dsDNA, E1 demonstrated a superb selectivity towards G-quadruplex DNA.•The characteristics of G-Quadruplex binding property, cytotoxicity and cell imaging were investigated through experimental and modeling studies. G-quadruplex DNA plays a very important role in clinical diagnosis and fluorescence analysis has attracted extensive attention. A class of carbazole-based fluorescent probes for the detection of G-quadruplex DNA was established in this work. In this system, the installation of an oligo(ethylene glycol) chain on the scaffold will improve the water-solubility and biocompatibility. The presence of styrene-like different side groups could tune the selectivity toward G-quadruplex DNA binding. Results revealed that the substitution pattern and position gave a great influence on the ability for the discrimination of the G-quadruplex from other DNA structures. Especially, probe E1 bound to G-quadruplex DNA with superior selectivity, which exhibiting almost no fluorescence response in the presence of non-G-quadruplex DNA structures. Comprehensive analyses revealed that E1 could bind both ends of the G-quadruplex, resulting in a significant increase of fluorescence emission intensity. Cellular uptake assay suggested that E1 could pass through membrane and enter living cells with low cytotoxicity.