Tuning the Selectivity of Ruthenium-Based Luminescent G-Quadruplex Probe by Triphenylamine Groups

Abstract

The overexpression of G-quadruplexes (G4) in tumor cells has been rendering them as important targets in tumor diagnosis and treatment. These non-canonical DNA secondary structures exhibit significant biological functions and potential applications, particularly in the development of anti-tumor drugs targeting these structures. However, there are relatively few studies on ruthenium complexes that can act as luminescence probes for G4 selective recognition. In this study, a new ruthenium complex was synthesized by using dipyrido[3,2-a:2′,3′-c]phenazine (dppz) as the parent ligand and introducing triphenylamine (TPA) group to create steric hindrance for ruthenium (II) complex. For the complex with parent dppz ligand, RC1 exhibited strong binding affinities for both G4 and double-stranded DNA, but displayed moderate selectivity toward 22AG-KCl. Upon introducing one triphenylamine group onto the main ligand, the binding affinity of complex RC2 for double-stranded DNA decreased significantly, resulting in 28-fold more selectivity toward 22AG-KCl than double-stranded DNA. The experimental results demonstrate that the appropriate introduction of steric hindrance groups can enhance the recognition selectivity of ruthenium complexes for G-quadruplex DNA by reducing its binding affinity for double-stranded DNA.