The mystery of sub-picosecond charge transfer following irradiation of hydrated uridine monophosphate

The early mechanisms by which ionizing rays damage biological structures by so-called direct effects are largely elusive. In a recent picosecond pulse radiolysis study of concentrated uridine monophosphate solutions [J. Ma, S. A. Denisov, J.-L. Marignier, P. Pernot, A. Adhikary, S. Seki and M. Mostafavi, J. Phys. Chem. Lett., 2018, 9, 5105], unexpected results were found regarding the oxidation of the nucleobase. The signature of the oxidized nucleobase could not be detected 5 ps after the electron pulse, but only the oxidized phosphate, raising intriguing questions about the identity of charge-transfer mechanisms that could explain the absence of U+. We address here this question by means of advanced first-principles atomistic simulations of solvated uridine monophosphate, combining Density Functional Theory (DFT) with polarizable embedding schemes. We contrast three very distinct mechanisms of charge transfer covering the atto-, femto- and pico-second timescales. We first investigate the ionization mechanism and subsequent hole/charge migrations on a timescale of attoseconds to a few femtoseconds under the frozen nuclei approximation. We then consider a nuclear-driven phosphate-to-oxidized-nucleobase electron transfer, showing that it is an uncompetitive reaction channel on the sub-picosecond timescale, despite its high exothermicity and significant electronic coupling. Finally, we show that non-adiabatic charge transfer is enabled by femtosecond nuclear relaxation after ionization. We show that electronic decoherence and the electronic coupling strength are the key parameters that determine the hopping probabilities. Our results provide important insight into the interplay between electronics and nuclear motions in the early stages of the multiscale responses of biological matter subjected to ionizing radiation.