Deprotonation reactions from oxygen in the a-L-rhamnose radical cation : a quantum chemical simulation study of radiation induced damage using DFT and TDDFT methods

Abstract

Damages from ionizing radiation to the sugar part of the DNA molecule may result in strand breaks. These are damages that can lead to mutations, cancer or cell death. Sugar damages in DNA can be studied experimentally by use of electron paramagnetic resonance (EPR) spectroscopy. In order to obtain a more complete understanding of the processes that occur immediately after irradiation, quantum chemical calculations are also more and more becoming an indispensable tool.

When carbohydrates in the condensed phase are oxidized by ionizing radiation, cation radicals and free electrons are generated. These products then partake in subsequent chemical reactions. In order to restore charge balance, the cations may send off a proton, deprotonate. Deprotonation reactions from hydroxyl groups (leaving neutral oxygen-centered radicals) have been studied in the carbohydrate α-L-rhamnose (C3H12O5). Rhamnose has four hydroxyl groups; all are possible positions for deprotonation reactions. The radiation-induced radicals in this sugar have been examined by EPR spectroscopy (Samskog and Lund 1980; Budzinski and Box 1985), but only one oxygen-centered radical was found, indicating that deprotonation selectively occurs from one of the four possible positions. Theoretical quantum chemical calculations based on density functional theory (DFT) later confirmed (Pauwels et al. 2008) that the oxygen-centered radical in rhamnose is deprotonated at the O4 position, yet no explanation was found for the observed selectivity.

In the present work, the electronic ground-state energy profiles for deprotonation from all four hydroxyl groups in rhamnose have been examined theoretically by means of DFT calculations. Both periodic boundary conditions, a two-layered cluster approach (ONIOM) and single molecule calculations have been used. Calculations of EPR properties of the obtained structures indicate that the periodic calculations are able to describe the experimentally observed radical. The energy profiles for the four different deprotonation reactions clearly indicate that deprotonation from O4 is both thermodynamically and kinetically preferred. Although these calculations would explain the observed preference for the O4-centered radical, the calculated energy barrier for the deprotonation reaction is still much higher than the thermal energy available at the typically low temperature of the experiments (4 K and 77 K). Hence, in the electronic ground state, the deprotonation reaction would not be likely to occur.

One possible explanation is that excited states are involved in the radical formation. The deprotonation may well occur before the molecule relaxes into the electronic and vibrational ground states after the initial ionization event. In order to investigate the possible role of excited electronic states of the cation, the excited states of have been examined by time-dependent DFT (TDDFT). The excited states were calculated throughout the deprotonation reactions and energy profiles were made. The attention has been focused on finding states with a lower energy barrier for the deprotonation reactions than the ground state and/or conical intersections with the ground state potential energy surface. So far, no such state has been found, but analyses still remain to be done. In order to get a better understanding for the abilities and potential of the TDDFT method, benchmark calculations have also been performed on three small molecules (H2O, CH3 and CO+) for which experimental data are available for comparisons.