Reversible photoswitching of RNA hybridization at room temperature with an azobenzene C-nucleoside

Chemistry. 2015 Feb 9;21(7):2845-54. doi: 10.1002/chem.201405840. Epub 2014 Dec 23.


Photoregulation of RNA remains a challenging task as the introduction of a photoswitch entails changes in the shape and the stability of the duplex that strongly depend on the chosen linker strategy. Herein, the influence of a novel nucleosidic linker moiety on the photoregulation efficiency of azobenzene is investigated. To this purpose, two azobenzene C-nucleosides were stereoselectively synthesized, characterized, and incorporated into RNA oligonucleotides. Spectroscopic characterization revealed a reversible and fast switching process, even at 20 °C, and a high thermal stability of the respective cis isomers. The photoregulation efficiency of RNA duplexes upon trans-to-cis isomerization was investigated by using melting point studies and compared with the known D-threoninol-based azobenzene system, revealing a photoswitching amplitude of the new residues exceeding 90 % even at room temperature. Structural changes in the duplexes upon photoisomerization were investigated by using MM/MD calculations. The excellent photoswitching performance at room temperature and the high thermal stability make these new azobenzene residues promising candidates for in-vivo and nanoarchitecture photoregulation applications of RNA.

Keywords: RNA; azobenzenes; nucleic acids; photoisomerization; photoswitches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azo Compounds / chemistry*
  • Hybridization, Genetic
  • Molecular Structure
  • Nucleosides / chemistry*
  • Oligonucleotides
  • RNA / chemistry*


  • Azo Compounds
  • Nucleosides
  • Oligonucleotides
  • RNA
  • azobenzene