Single-Photon DNA Photocleavage up to 905 nm by a Benzylated 4-Quinolinium Carbocyanine Dye

This paper describes the DNA interactions of near-infrared (NIR) benzylated 4-quinolinium dicarbocyanine dyes containing a pentamethine bridge meso-substituted either with a bromine (4) or hydrogen (5) atom. In pH 7.0 buffered aqueous solutions, the 4-quinolinium dyes absorb light that extends into the near-infrared range up to ∼950 nm. The unique direct strand breakage of pUC19 DNA that is sensitized by irradiating either dicarbocyanine with an 850 nm LED laser constitutes the first published example of DNA photocleavage upon single-photon chromophore excitation at a wavelength greater than 830 nm. Brominated dye 4, which is more stable than and achieves DNA strand scission in higher yield than its hydrogen-bearing counterpart 5, cleaves plasmid DNA under 830 and 905 nm laser illumination. The addition of increasing amounts of DNA to aqueous pH 7.0 solutions converted an aggregated form of dye 4 to a monomer with bathochromic absorption that overlaps all three laser emission wavelengths. No induced circular dichroism and fluorescence signals were detected when DNA was present, pointing to possible external binding of the dye to the DNA. Experiments employing radical-specific fluorescent probes and chemical additives showed that brominated dye 4 likely breaks DNA strands by photosensitizing hydroxyl radical production. Micromolar concentrations of the dye were relatively nontoxic to cultured Escherichia coli cells in the dark but dramatically reduced survival of the cells under 830 nm illumination. As NIR light wavelengths deeply penetrate biological tissues, we envisage the future use of carbocyanine dyes as a sensitizing agent in phototherapeutic applications.