Azobenzene as a photoregulator covalently attached to RNA: a quantum mechanics/molecular mechanics-surface hopping dynamics study

The photoregulation of nucleic acids by azobenzene photoswitches has recently attracted con- siderable interest in the context of emerging biotechnological applications. To understand the mechanism of photoinduced isomerisation and conformational control in these complex biologi- cal environments, we employ a Quantum Mechanics/Molecular Mechanics (QM/MM) approach in conjunction with nonadiabatic Surface Hopping (SH) dynamics. Two representative RNA- azobenzene complexes are investigated, both of which contain the azobenzene chromophore covalently attached to an RNA double strand via a β -deoxyribose linker. Due to the pronounced constraints of the local RNA environment, it is found that trans-to-cis isomerization is slowed down to a time scale of ∼15 picoseconds, in contrast to 500 femtoseconds in vacuo, with a quantum yield reduced by a factor of two. By contrast, cis-to-trans isomerization remains in a sub-picosecond regime. A volume-conserving isomerization mechanism is found, similarly to the pedal-like mechanism previously identified for azobenzene in solution phase. Strikingly, the chiral RNA environment induces opposite right-handed and left-handed helicities of the ground-state cis-azobenzene chromophore in the two RNA-azobenzene complexes, along with an almost com- pletely chirality conserving photochemical pathway for these helical enantiomers.