Binding Modes and Near Infrared Photo Cleavage of DNA by Pentamethine Bridged Phenanthridinium and Quinolinium Carbocyanine Dyes

Cyanine dyes have been used for labeling biomolecules such as proteins and DNA. The fluorescent properties and possibility of photosensitization by these molecules made them candidate drugs in image-guided surgery and in photodynamic therapy (PDT). In this study, we are exploring the theranostic properties of novel cyanine dyes with a goal to find near infrared photo nucleases in order to achieve an ideal photosensitizer that could be potentially used in PDT. Duplex DNA photo cleavage by pentamethine bridged near infrared cyanine dye was investigated. The detailed chemistry of dyes photo physical and photochemical properties, mechanism of dye-DNA interactions, DNA binding modes, and species involved in photo cleavage reactions were studied. The effects of different types of heterocyclic rings, variation in the length of the polymethine bridge, and the effect of electron withdrawing substitution on the dyes were investigated with a goal to achieve a new generation NIR drugs in photo therapy

DNA Photocleavage in the Near-Infrared Wavelength Range by 2-Quinolinium Dicarbocyanine Dyes

Here, we report the syntheses of two pentamethine cyanine dyes containing quinolinium rings and substituted with either hydrogen (3) or bromine (4) at the meso carbon. The electron withdrawing bromine atom stabilizes dye 4 in aqueous buffer, allowing complex formation to occur between the dye and double-helical DNA. UV–visible, CD, and fluorescence spectra recorded at low DNA concentrations suggest that dye 4 initially binds to the DNA as a high-order aggregate. As the ratio of DNA to dye is increased, the aggregate is converted to monomeric and other low-order dye forms that interact with DNA in a non-intercalative fashion. The brominated dye 4 is relatively unreactive in the dark, but, under 707–759 nm illumination, generates hydroxyl radicals that cleave DNA in high yield (pH 7.0, 22 °C). Dye 4 is also taken up by ES2 ovarian carcinoma cells, where it is non-toxic under dark conditions. Upon irradiation of the ES2 cells at 694 nm, the brominated cyanine reduces cell viability from 100 ± 10% to 14 ± 1%. Our results suggest that 2-quinolinium-based carbocyanine dyes equipped with stabilizing electron withdrawing groups may have the potential to serve as sensitizing agents in long-wavelength phototherapeutic applications