The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases.

Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the  ω B97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48  × 10 − 13  cm³ molecules⁻¹s⁻¹ for adenine, 1.02  × 10 − 11  cm³ molecules⁻¹s⁻¹ for guanine, 5.52  × 10 − 13  cm³ molecules⁻¹s⁻¹ for thymine, 1.47  × 10 − 13  cm³ molecules⁻¹s⁻¹ for cytosine and 7.59  × 10 − 14  cm³ molecules⁻¹s⁻¹ for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics. [ABSTRACT FROM AUTHOR]