An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies

• Published in: Analytica chimica acta 2023-04, Vol.1252, p.341074-341074, Article 341074
• Main Authors: Lang, Xue-Xian, Sun, Shu-Hui, Cao, Hao-Wen, Chen, Yan-Song, Li, Hong-Yao, Wang, Ming-Qi
• Format: Article
• Language: English
• Subjects: DNA - chemistry; Environmentally insensitive; Fluorescence; Fluorescent Dyes - chemistry; Fluorescent probe; G-Quadruplexes; G4 DNA; High-fidelity; Humans
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2023.341074

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a “fluorescence-off” state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems. [Display omitted] •An environmentally insensitive D-A type fluorescence probe ACPS was designed.•This probe with desirably always initial “fluorescence-off” state in various solvents.•Selective fluorescence lighting-up recognition of G4 DNA was presented.•The mechanism by which the probe recognized G4 DNA was revealed.