Formation of Cyclobutane Dimers from the Solvated Uracil Stacks

Abstract

In the biological environment, RNA is prone to absorb UV light upon which the formation of intra- and inter-strand crosslinks of cyclobutane-type is possible. Mutual orientation of the nucleobases could be important since it could lead to the different photochemical products. To resolve photochemistry behind this, comparative nonadiabatic molecular dynamics study of microsolvated face-to-back (F2B) and face-to-face (F2F) stacked uracil clusters is performed using the second-order algebraic-diagrammaticconstruction (ADC(2)) method. Around the half of the simulated trajectories of the microsolvated F2B stacks excited at 260 nm relaxed non-reactively to the ground state by an ethylenic twist around the one of the uracils C=C bond (ππ*/S0 CoIn) and the other half remained in the lowest nπ* state in which stack dissociation is observed. The dissociation of the F2B stack rule out possibility of the cyclobutane uracil dimer (CUD) formation through the triplet manifold (3ππ* state). However, somewhat constrained translational motion of the uracils within the RNA environment could still facilitate dimerization. Photodynamics observed on this model system suggest low propensity towards CUD formation for the F2B stacks, i.e., intra-strand CUD between adjacent RNA uracils. On the other hand, analysis of the microsolvated F2F uracil stacks simulated trajectories revealed several pro-reactive trajectories in which nascent CUD product could be recognized. At the end of the simulated trajectories F2F stack reside near ππ*/S0 CoIn. These findings confirm, on the qualitative level, experimental finding that there is a greater tendency of RNA to form inter-strand cyclobutane-type crosslinks, i.e., cyclobutane-type products between the bases that are geometrically close, but distant in the primary structure. Example of such geometrical arrangement occurs in the RNA hairpin loops.