Spectroscopic Investigation of the Quadruplex DNA-Binding Properties of 9-Aryl-Substituted Isoquinolinium Derivatives

Abstract

The spectroscopic investigation of the binding properties of berberine-type 9-aryl-substituted isoquinolinium derivatives with G-quadruplex DNA (G4-DNA) are presented. Photometric titrations show that these ligands bind with high affinity to the telomeric G4-DNA form 22AG (K=1.0–44×105 M−2). Furthermore, fluorimetric analysis of thermal DNA denaturation (FRET melting) reveals a significant thermal stabilization of G4-DNA 22AG upon association with the methoxy-substituted derivatives. As an analytically useful property, the derivatives with a phenyl substituent or with additional electron-donating groups show a very weak fluorescence intensity, which increased significantly upon G4-DNA complexation (fluorescence light-up effect). Additional time-resolved fluorescence spectroscopy indicated increased fluorescence lifetimes of the DNA-bound 9-(4-methoxyphenyl)-substituted derivative, when interacting with the quadruplex-forming strand 22AG. Notably, the changes of the steady-state and time-resolved emission properties of the ligand are more pronounced with G4-DNA than with duplex DNA so that the combination of these complementary methods may be used for the selective G4-DNA detection.