Hydroquinone-functionalized cyanine dye as reduction-sensitive probe for imaging of biological reducing species

Abstract

The redox chemistry and status of different cell types and tissues has still not been well understood and thus represents a major focus for the development of novel responsive fluorophores. In this context, there is an ongoing search for reduction-sensitive probes that can globally or specifically image reducing environments or species in biological settings. Here, the synthesis and characterization of responsive cyanine dyes operating in the near-infrared (NIR) is reported based on the use of the hydroquinone/quinone and catechol/quinone couple. The introduction of a hydroquinone group into the meso-position of an indodicarbocyanine dye via a Suzuki cross-coupling reaction created a water-soluble fluorescent “on-off-on” probe whose fluorescence can be modulated through oxidation and reduction. By adding biologically relevant reducing species, such as glutathione, cysteine or ascorbate, the “off”-probe could be rapidly turned on around 660 nm within 30 s. Reversible switching between the “on” and “off” form was demonstrated. Furthermore, the sensor was applied in confocal microscopy studies as a reduction-sensitive probe for bioimaging in living cells.