Preferential Recognition of Human Telomeric G-Quadruplex DNA by a Red-Emissive Molecular Rotor

The development of new fluorescent molecules for the recognition of specific G-quadruplex DNA structures has attracted wide attention due to their diverse roles in drug design, sensing, and cellular probing. In this work, we report the discovery of a red-emissive styryl quinolinium-based molecular rotor (compound 1), which recognizes human telomeric G-quadruplex with a distinct preference over DNA duplexes. Optical spectroscopy (UV-vis and circular dichroism)-based experiments indicated discernible interaction of compound 1 with the human telomeric DNA G-quadruplex with features of stacking interactions. Fluorescence-based Job's plot revealed a 1:1 binding stoichiometry between compound 1 and the human telomeric DNA G-quadruplex, and subsequent titration experiments showed micromolar affinities (K_a = 0.51 × 10⁶ M^-1). Molecular docking experiments showed interactions of compound 1 in the grooves of the quadruplex. Finally, we provide the application of compound 1 as a reporter molecule in the fluorescence displacement experiments, which showed its ability to act as a fluorescent probe compatible with ligands having aromatic cores.