Synthesis, Self-Assembly, and Nucleic Acid Recognition of an Acylhydrazone-Conjugated Cationic Tetraphenylethene Ligand

Abstract

Supramolecular polymers are of interest in the pursuit of multivalent nucleic acids recognition. However, their formation often relies on non-covalent forces that are also at play in the interaction with nucleic acids. In this work, we designed a novel compound (TPE-Gir) combining a tetraphenylethene aromatic core tethered to four quaternary ammoniums through acylhydrazone spacers, and we investigated in detail its self-assembly and interaction with different types of nucleic acids. The spectroscopic analyses indicate the self-assembly of regular fluorescent nanoparticles (observed by DLS and TEM) in the absence of nucleic acids, the strong propensity to intercalate into single-stranded DNA, the ability to bind into the minor groove of double-stranded DNA, and the selective binding to G-quadruplex (G4) structures by fitting within a wide G4-groove. Those recognition events are quantified by isothermal titration calorimetry and the proposed binding models are supported by docking simulations.