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.