Theoretical Characterization of the Reduction Potentials of Nucleic Acids in Solution.

Valeria D’Annibale,Andrea Amadei,Marco D’Abramo,Alessandro Nicola Nardi

doi:10.1021/acs.jctc.0c00728

Abstract

Here, we present the theoretical–computational modeling of the oxidation properties of four DNA nucleosides and nucleotides and a set of dinucleotides in solutions. Our estimates of the vertical ionization energies and reduction potentials, close to the corresponding experimental data, show that an accurate calculation of the molecular electronic properties in solutions requires a proper treatment of the effect of the environment. In particular, we found that the effect of the environment is to stabilize the oxidized state of the nucleobases resulting in a remarkable reduction—up to 6.6 eV—of the energy with respect to the gas phase. Our estimates of the aqueous and gas-phase vertical ionization energies, in good agreement with photoelectron spectroscopy experiments, also show that the effect on the reduction potential of the phosphate group and of the additional nucleotide in dinucleotides is rather limited.

Highlights

Oxidation of the DNA is involved in very important processes such as DNA damage and long-range DNA charge transfer
Such an approach does not suffer from the limitations described above, for example, the vertical ionization energy (VIE) is measured from the instantaneous electron detachment, photoelectron spectroscopy (PES) is not able to provide an estimate of the free energy of the process
We present a statistical−mechanical sound approach where the effect of the perturbation is treated by means of the perturbed matrix method,[27,28] which combines the extended sampling as provided by classical molecular dynamics (MD) simulations and high-level quantum mechanical calculations

Summary

Introduction

Oxidation of the DNA is involved in very important processes such as DNA damage and long-range DNA charge transfer. Its determination via electrochemical approaches suffers by low solubility and by the irreversible nature of the process.[7] Alternatively, the characterization of the vertical ionization potential of single and small oligonucleotides has been addressed by means of the photoelectron spectroscopy (PES) technique.[10,11] such an approach does not suffer from the limitations described above, for example, the vertical ionization energy (VIE) is measured from the instantaneous electron detachment, PES is not able to provide an estimate of the free energy of the process For these reasons, the characterization of the DNA oxidation has stimulated the applications of several theoretical−computational approaches.[12−26] In these studies, the quantum mechanical calculations on the nucleobases are performed in the gas phase and the effect of the environment is taken into account by means of dielectric continuum models. Similar to the Received: July 13, 2020 Published: February 23, 2021

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Conclusion