Analogs of Changsha near-infrared dyes with large Stokes Shifts for bioimaging

The construction of fluorescent imaging probes has contributed significantly to the recent advances in biology and medicine. Near infrared (NIR) fluorescent probes are favorable to be employed in fluorescence imaging in living animals. Rhodamine dyes have been widely used as a robust platform for development of fluorescent probes for a wide variety of targets. However, the absorption and emission wavelengths of classical rhodamine derivatives are below 600 nm. Thus, it is desirable to construct rhodamine analogs with longer absorption and emission wavelengths, preferably in the NIR region. Toward this end, our group has previously constructed Changsha (CS) NIR dyes while retaining the rhodamine-like fluorescence ON-OFF switching mechanism. However, like classic rhodamines, these rhodamine NIR derivatives still have small Stokes shifts (typically less than 35 nm), which can lead to serious self-quenching and fluorescence detection error due to excitation backscattering effects. This shortcoming may constrain the full potential of their applications. Thus, there is a need to develop rhodamine NIR derivatives with large Stokes shifts. In this work, we have designed and synthesized a class of analogs of CS NIR dyes with large Stokes shifts. Among the new dyes presented herein, the dye 1c displays a high fluorescence quantum yield in biological media and thus promising for in vivo imaging applications. Furthermore, using 1c as a platform, we further constructed the NIR fluorescent turn-on probe 3, which is suitable for imaging endogenously produced HClO in the RAW264.7 macrophage cells, demonstrating the value of our new NIR functional fluorescent dye 1c. (C) 2013 Elsevier Ltd. All rights reserved.