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

TL;DR

A new dye can cut DNA using near-infrared light up to 905 nm, with potential for phototherapy.

Contribution

First example of DNA photocleavage using single-photon excitation beyond 830 nm.

Findings

Brominated dye 4 achieves higher DNA cleavage efficiency than its hydrogen counterpart.

Dye 4 induces DNA strand breakage via photosensitized hydroxyl radical production.

Dye 4 is nontoxic in the dark but reduces E. coli survival under 830 nm light.

Abstract

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.

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