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Oxidation Pathways in Adenine and Guanine in Aqueous Solution from First Principles Electrochemistry
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics, Quantum Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2004 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 6, 4707-4713 p.Article in journal (Refereed) Published
Abstract [en]

The 8-oxo-7,8-dehydropurine tautomers (8-oxoA and 8-oxoG) are mutagenic lesions found in DNA. Two experimental pathways have been proposed for the formation of 8-oxoG: one initiated by deprotonation of the OH˙ radical adduct at the 8-position of guanine (G8OH˙) and the other initiated by a proton-coupled one-electron oxidation of G8OH˙. We here report standard Gibbs energies of the above processes involving proton transfer (PT), electron transfer (ET), and proton-coupled electron transfer (PT–ET) reactions calculated from first principles using DFT (B3LYP) and a continuum solvent model (IEF-PCM). The computed data show that the former pathway is unlikely to occur for A8OH˙ and G8OH˙ in neutral aqueous solution, because of the very low acidity of the hydrogen at the 8-position. In contrast, the latter route involving proton-coupled one-electron oxidations of A8OH˙ and G8OH˙ are exergonic by about 25 kcal mol−1 in aqueous solution. Energetically, adenine and guanine behave similarly toward oxidation to yield 8-oxoA and 8-oxoG. However, the calculated standard Gibbs energetics confirms that the ease of ionization of the native and oxidized forms of nucleobases B to yield the radical cations B˙+ or their deprotonation products B(–H)˙ is 8-oxoG > G > 8-oxoA > A > C > T in aqueous solution. Consequently, 8-oxoG will most readily trap radical cations and neutral radicals in DNA, since it can reduce any nucleobase radical cation B˙+ (via ET) or its deprotonation product B(–H)˙ (via PT–ET) back to the native form of the nucleobase.

Place, publisher, year, edition, pages
2004. Vol. 6, 4707-4713 p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-91640DOI: 10.1039/B410922HOAI: oai:DiVA.org:uu-91640DiVA: diva2:164439
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2013-09-11Bibliographically approved
In thesis
1. Modern Computational Physical Chemistry: An Introduction to Biomolecular Radiation Damage and Phototoxicity
Open this publication in new window or tab >>Modern Computational Physical Chemistry: An Introduction to Biomolecular Radiation Damage and Phototoxicity
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Modern fysikalisk-kemisk beräkningsmetodik : En introduktion till biomolekylära strålningsskador och fototoxicitet
Abstract [en]

The realm of molecular physical chemistry ranges from the structure of matter and the fundamental atomic and molecular interactions to the macroscopic properties and processes arising from the average microscopic behaviour.

Herein, the conventional electrodic problem is recast into the simpler molecular problem of finding the electrochemical, real chemical, and chemical potentials of the species involved in redox half-reactions. This molecular approach is followed to define the three types of absolute chemical potentials of species in solution and to estimate their standard values. This is achieved by applying the scaling laws of statistical mechanics to the collective behaviour of atoms and molecules, whose motion, interactions, and properties are described by first principles quantum chemistry. For atomic and molecular species, calculation of these quantities is within the computational implementations of wave function, density functional, and self-consistent reaction field theories. Since electrons and nuclei are the elementary particles in the realm of chemistry, an internally consistent set of absolute standard values within chemical accuracy is supplied for all three chemical potentials of electrons and protons in aqueous solution. As a result, problems in referencing chemical data are circumvented, and a uniform thermochemical treatment of electron, proton, and proton-coupled electron transfer reactions in solution is enabled.

The formalism is applied to the primary and secondary radiation damage to DNA bases, e.g., absorption of UV light to yield electronically excited states, formation of radical ions, and transformation of nucleobases into mutagenic lesions as OH radical adducts and 8-oxoguanine. Based on serine phosphate as a model compound, some insight into the direct DNA strand break mechanism is given.

Psoralens, also called furocoumarins, are a family of sensitizers exhibiting cytostatic and photodynamic actions, and hence, they are used in photochemotherapy. Molecular design of more efficient photosensitizers can contribute to enhance the photophysical and photochemical properties of psoralens and to reduce the phototoxic reactions. The mechanisms of photosensitization of furocoumarins connected to their dark toxicity are examined quantum chemically.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 80 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 965
Biology, statistical mechanics, biophysical chemistry, interface, surface thermodynamics, bioelectrochemistry, ionizing radiation, radiation therapy, condensed matter, computational chemistry, nucleic acids, radiation damage, electrode potential, electronic transport, photochemistry, strand break, photodynamic action, cytostatic, solvation, solvated electron, absolute potential, chemical potential, Biologi
National Category
Biological Sciences
urn:nbn:se:uu:diva-4224 (URN)91-554-5940-4 (ISBN)
Public defence
2004-05-03, B42, BMC, Husargatan 3, Uppsala, 09:15
Available from: 2004-04-08 Created: 2004-04-08Bibliographically approved

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