Bioaggregachromism of Asymmetric Monomethine CyanineDyes as Noncovalent Binders for Nucleic Acids

Abstract

Two new asymmetric monomethine cyanine dyes, featuring dimethoxy quinoliniumor methyl quinolinium end groups and benzothiazole or methyl benzothiazole endgroups were synthesized. The chemical structures of the two dyes—(E)-6,7-dimethoxy-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium iodide (3a) and(E)-4-((3,5-dimethylbenzo[d]thiazol-2(3H)-ylidene)methyl)-1,2-dimethylquinolin-1-ium iodide(3b)—were confirmed through NMR spectroscopy and MALDI-TOF mass spectrometry.A new methodology was developed to study monocationic dyes in the absence of amatrix and cationizing compounds in MALDI-TOF mass experiments. The newly synthesizeddyes contain hydrophobic functional groups attached to the chromophore, enhancingtheir affinity for the hydrophobic regions of nucleic acids within the biological matrix. Thedyes’ photophysical properties were investigated in aqueous solutions and DMSO, as wellas in the presence of nucleic acids. The dyes exhibit notable aggregachromism in both pureaqueous and buffered solutions. The observed aggregation phenomena were further elucidatedusing computational methods. Fluorescence titration experiments revealed that uponcontact with nucleic acids, the dyes exhibit bioaggregachromism–aggregachromism on thesurfaces of the respective biomolecular matrix (RNA or DNA). This bioaggregachromismwas further confirmed by CD spectroscopy. Given the pronounced aggregachromismdetected, we conclude that the dyes investigated in this study are highly suitable for useas fluorogenic probes in biomolecular recognition techniques. The unique absorption andfluorescence spectra of these dyes make them promising fluorogenic markers for variousbioanalytical methods related to biomolecular recognition.