Preferential Binding of a Red Emissive Julolidine Derivative to a Promoter G‐Quadruplex

Abstract

The therapeutic potential of G‐quadruplexes has increased significantly with the growing understanding of their functional roles in pathogens apart from human diseases such as cancer. Here, we report the synthesis of three julolidine‐based molecules and their binding to nucleic acids. Among the synthesized molecules, compound 1 exhibited red emissive fluorescence with a distinct preference for Pu22 G‐quadruplex. The binding of compound 1 to Pu22 G‐quadruplex, initially identified through a fluorescence‐based screening, was further confirmed by UV‐vis, fluorescence spectroscopy, and circular dichroism‐based experiments. Thermal denaturation of compound 1 in the presence of Pu22 G‐quadruplex revealed a concentration‐dependent stabilization (~10.0 °C at 1 : 3 stoichiometry). Fluorescence‐based experiments revealed 1 : 1 stoichiometry of the interaction and an association constant (Ka) of 5.67×106 M−1. CD experiments displayed that the parallel conformation of the G‐quadruplex was retained on compound 1’s binding and signs of higher order binding/complex formation were observed at high compound 1 to DNA ratio. Molecular docking studies revealed the dominance of stacking and van der Waals interactions in the molecular recognition which was aided by some close‐distance interactions involving the quinolinium nitrogen atom.