TY - JOUR

T1 - The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases

AU - Ekstrøm, Anna Thorn

AU - Hansen, Vera Staun

AU - Sauer, Stephan P. A.

PY - 2024

Y1 - 2024

N2 - 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 ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction has been 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

AB - 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 ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction has been 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

KW - Faculty of Science

KW - Radiation Therapy

KW - DNA

KW - OH radical

KW - nucleobases

U2 - 10.3390/ijms25063118

DO - 10.3390/ijms25063118

M3 - Journal article

VL - 25

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 6

M1 - 3118

ER -