Development of Red-Shifted and Fluorogenic Nucleoside and Oligonucleotide Diarylethene Photoswitches.

Abstract

The reversible modulation of fluorescence signals by light is of high interest for applications in super‐resolution microscopy, especially on the DNA level. In this article we describe the systematic variation of the core structure in nucleoside‐based diarylethenes (DAEs), in order to generate intrinsically fluorescent photochromes. The introduction of aromatic bridging units resulted in a bathochromic shift of the visible absorption maximum of the closed‐ring form, but caused reduced thermal stability and switching efficiency. The replacement of the thiophene aryl unit by thiazol improved the thermal stability, whereas the introduction of a benzothiophene unit led to inherent and modulatable turn‐off fluorescence. This feature was further optimized by introducing a fluorescent indole nucleobase into the DAE core, resulting in an effective photoswitch with a fluorescence quantum yield of 0.0166 and a fluorescence turn‐off factor of 3.2. The site‐specific incorporation into an oligonucleotide resulted in fluorescence‐switchable DNA with high cyclization quantum yields and switching efficiency, which may facilitate future applications.