Selective aggregation of natural ligands into efficient AIEgens on a human telomeric duplex-G-quadruplex junction

DNA structures with the potential to concurrently recruit multiple ligands are promising in pharmaceutical and sensing applications when concentrated in a local environment. Herein, we found that human telomeric G-quadruplex (htG4) structures with a junction can selectively aggregate a natural ligand of tetrahydropalmatine (THP) into AIEgens. The htG4 monomer favors formation of a THP dimer emitting at ∼525 nm. In addition, only a hybrid htG4 folding supports formation of the emissive THP dimer. However, overhanging a duplex beyond the 5' end of the hybrid htG4 structure preferentially forms THP J-aggregates with member molecularity being more than two. It is demonstrated that the junction between the duplex and the hybrid htG4 structure is responsible for formation of the THP J-aggregates, as confirmed by the fact that the pairing state of the junction affects the molecularity of the J-aggregates. Nevertheless, such J-aggregates cannot be grown at the junction of two tandem htG4s. Therefore, G4-initiated ligand aggregation (GILA) for natural compounds provides a new way to design pharmaceuticals and sensors with a high local concentration at the site of interest.