Development of High‐Performance Pyrimidine Nucleoside and Oligonucleotide Diarylethene Photoswitches

Abstract

Nucleosidic and oligonucleotidic diarylethenes (DAEs) are an emerging class of photochromes with high application potential. However, their further development is hampered by the poor understanding of how the chemical structure modulates the photochromic properties. Here we synthesized 26 systematically varied deoxyuridine-and deoxycytidine-derived DAEs and analyzed reaction quantum yields, composition of the photostationary states, thermal and photochemical stability, and reversibility. This analysis identified two high-performance photoswitches with near-quantitative, fully reversible back-and-forth switching and no detectable thermal or photochemical deterioration. When incorporated into an oligonucleotide with the sequence of a promotor, the nucleotides maintained their photochromism and allowed the modulation of the transcription activity of T7 RNA polymerase with an up to 2.4-fold turnoff factor, demonstrating the potential for optochemical control of biological processes.

“Click-switch” – one-step conversion of organic azides into photochromic diarylethenes for the generation of light-controlled systems

“…12(e)). Ring closing and ring opening quantum yields were determined as reported previously 58,59 and indicate a rather efficient photochemistry. A most striking feature is the high quantum yield of ring opening upon irradiation with 505 nm visible light (0.56), which compares favorably with classical dithienylethenes where this value is oen smaller than 0.01.…”

Photochemical modifications for DNA/RNA oligonucleotides

“…20). 163 In particular, the photochromism (e.g., quantum yields, composition of the photostationary states, thermal and photochemical stability, and reversibility) of the modied dU with 2-Py or Ph t Bu was maintained in the environment of the single-stranded oligonucleotide, and for Ph t Bu even in the duplex. These modications were also shown to be useful in controlling transcriptional activation.…”

“…These modications were also shown to be useful in controlling transcriptional activation. 163 Reaction characteristics. The characteristic absorption bands of the diarylethene chromophore at l ¼ 242 nm and l ¼ 305 nm are detectable in the UV/Vis spectrum of the modied nucleoside (colorless solutions-yellow).…”

“…The open-ring form containing promoters showed almost the same activity as the unmodied controls, whereas a $2 fold decrease in the transcription rate was observed for the closed form aer UV irradiation. 163…”

Development of Red‐Shifted and Fluorogenic Nucleoside and Oligonucleotide Diarylethene Photoswitches

“…which thiophene substituent we chose, λ max,vis turned out to be limited to 505-510 nm, [18,19] which will likely limit future applications in biological tissues. Another interesting property known from certain classical DAEs is intrinsic, switchable fluorescence.…”