Tricationic asymmetric monomeric monomethine cyanine dyes with chlorine and trifluoromethyl functionality – Fluorogenic nucleic acids probes

Abstract

The nucleic acids staining ability of a series asymmetric monomeric monomethine cyanine dyes prepared by simple and reliable synthetic procedure is demonstrated. The dyes show ratiometric red shift of their longer wavelength absorption maxima. It is in the range 514–522 nm neat in TE buffer, 516–528 nm in the presence of DNA, and 518–524 nm in the presence of RNA. Practically the target dyes are not fluorescent in water solutions or possess negligible fluorescence, but become strongly fluorescent after contacting with nucleic acids. A considerable increase of the fluorescence intensity upon binding to RNA compared to dsDNA is observed particularly in the group of chlorine substituted analogues 1a-1c. The intensive ICD signal of dye 1a in the presence of RNA unequivocally proves that finding. Molecular docking studies have been performed to investigate the nature of binding mode of the dyes with DNA. 1a-1c are groove binders and 2b-2c are interacting with DNA through partial intercalation mode. The nature of electronic transitions and their manifestation in the electronic spectra are revealed by DFT and TDDFT calculations.