The N-biphenyldihydroisoquinolinium scaffold as a novel motif for selective fluorimetric detection of quadruplex DNA

Abstract

The spectroscopic investigation of the DNA-binding properties of (S)-6,8-dimethoxy-2-(4′-methoxy-[1,1′-biphenyl]-4-yl)-1,3-dimethyl-3,4-dihydroisoquinolin-2-ium revealed the cationic donor-acceptor-substituted biaryl unit as a promising motif for selective fluorimetric detection of particular quadruplex DNA (G4-DNA) forms. The title compound exhibits the characteristic solvent-dependent dual emission of biaryl fluorophores; however, the emission quantum yields are very low (Φfl ≤ 0.01) because of radiationless deactivation of the excited state by conformational changes. In contrast, the emission intensity of the biaryl derivative increases by a factor of 2-10 on association with G4-DNA (KB = 8 × 104 M−1-4 × 105 M−1), because the structural relaxation of the exited ligand is suppressed in the binding site. The signal pattern of the dual emission, specifically the relative contribution of each band, varies with the different G4-quadruplex forms 22AG, c-kit, c-myc, c-kras, and h-ras1, most likely caused by the different dynamic flexbility of the ligand in the distinct binding sites. These effects enable the fluorimetric identification of sterically constrained binding sites, such as in c-kit and h-ras1, even with the naked eye.