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.

G4 DNA 结构高度定位于人类基因组中功能重要的位点，已被确定为调节多种生物过程的生物标志物。鉴定G4响应荧光探针在解决G4生物学功能、开发新的抗癌药物家族等方面具有广阔的应用前景。然而，目前设计的一些 G4 DNA 探针可能会受到严重的溶剂依赖性影响，并产生非特异性荧光，从而掩盖来自 G4 DNA 的特定信号。在此，我们将大体积咪唑核分子转子融合在咔唑-吡啶的 DA 结构单元中，构建了一个新的探针ACPS。这种具有理想的环境不敏感特性的新探针表现出“荧光关闭”” 在各种极性溶剂中的状态。在 G4 DNA 存在的情况下，分子内旋转将受到限制，从而引发强烈的荧光增强。特别是，探针ACPS以优异的选择性与 G4 DNA 结构结合，在非 G4 DNA 结构存在的情况下表现出更弱的荧光响应。该探针还能够在细胞成像中实现荧光可视化。总的来说，探针设计策略消除了不可控的环境极性变化引起的背景荧光，从而实现了复杂系统中 G4 DNA 结构的高保真传感。