DNA quadruplexes as molecular scaffolds for controlled assembly of fluorogens with aggregation-induced emission.

Aggregation-induced emission (AIE) can be generated due to the restriction of intramolecular motions. The controllable assembly of fluorogens with AIE properties (AIEgens) is able to provide a new opportunity for precise manipulation of fluorescent signal transduction. Here, a tetrapod DNA quadruplex (TP-G4) was designed as a molecular scaffold for assembly and precise modulation of light emission of an oligonucleotide-grafted fluorogen with aggregation-induced emission (Oligo-AIEgen). The Oligo-AIEgen was synthesized by attaching the AIEgen to the 3'-terminus of the oligonucleotide through a dibenzylcyclooctyne mediated coupling reaction. The AIEgen emitted no detectable fluorescence in the context of a double-stranded structure. When hybridized to the parallel-stranded TP-G4, several AIEgens were located in close proximity to generate fluorescence. The fluorescence intensity has been precisely regulated by manipulation of the spacer length between the core structure of the scaffold and AIEgen, as well as by altering the quartet number of the G-quadruplex. Similar control of fluorescence was also demonstrated using tetramolecular and bimolecular i-motif quadruplex structures as the scaffolds. These scaffolds provide a proof of concept on the manipulation of molecular interactions, which forms a universal molecular tool for the design of new biosensing strategies.