Biomimetic Hydrogen‐Bonded G ⋅ C ⋅ G ⋅ C Quadruplex within a Tetraphenylethene‐Based Octacationic Spirobicycle in Water

Abstract

AbstractIn 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.