Biomimetic Hydrogen-Bonded G•C•G•C Quadruplex within a Tetraphenylethene-Based Octacationic Spirobicycle in Water.

Abstract

In biological systems, nucleotide quadruplexes (such as G-quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen-bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen-bonded G•C•G•C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three-dimensional (3D) crossing dual-cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1:4 host-guest complexation in water. The X-ray structure reveals that four d(GpC) molecules further form a two-layer G•C•G•C quadruplex with Watson-Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non-covalent interactions of hydrogen bonds, CH···π interactions, and hydrophobic effect. Due to the dynamically-rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror-image CD spectra for the pH-dependent hydrogen-bonded assemblies of d(GpC) including the Watson-Crick G•C•G•C (pH 9.22) and Hoogsteen G•C+•G•C+ (pH 5.74) quartets through the host-guest chirality transfer in water.