Tropylium Derivatives as New Entrants that Sense Quadruplex Structures

Abstract

G-quadruplex (G4) is the most well-known noncanonical conformation of DNA involved in diverse pharmacological and biological contexts. G4 ligands have been actively developed as molecular probes and tumor therapeutic reagent candidates. They have also been used to detect the presence of G4s and identify their biological roles. Currently used ligands are commonly aromatic, planar, and electron deficient for effective interaction with G4s. Recognizing that tropylium cations possess the aforementioned features of effective G4 ligands, we prepared tropylium derivatives to validate their binding affinity with G4s. Titration against various DNA sequences revealed gradual changes in the UV–vis spectra of the tropylium derivatives. A strong hypochromic effect, indicating intercalation or π–π stacking, was observed when c-kit DNA was present in a binding ratio of 2:1 (ligand:DNA). The energetically minimized binding model showed that the G4–ligand complexes were stabilized by electrostatic interactions. Encouraged by the present findings, the application of tropylium derivatives in cellular contexts is underway.