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First Principles Electrochemical Study of Redox Events in DNA Bases and Chemical Repair in Aqueous Solution
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry, 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, 2426-2433 p.Article in journal (Refereed) Published
Abstract [en]

Primary and secondary radiation-induced damage to DNA, and chemical repair of the lesions on the nucleobases in solution involve a cascade of proton transfer (PT), electron transfer (ET), and proton-coupled electron transfer (PT-ET) reactions. The rate constants of these reactions depend on the standard Gibbs energy changes that can be derived from experiment. We here apply a first principles approach to calculate standard Gibbs energy changes of proton, electron, and proton-coupled electron transfer reactions in solution, wherein electrons and protons participate as independent ions; data that is fully compatible with that experimentally derived. Hence, the thermodynamic feasibility of ET and PT-ET pathways for these reactions depending on the effective concentration of hydrogen ions can be directly rationalized from first principles. The focus of this study is the primary and secondary ionization events in nucleobases in the presence of hydrogen atoms, solvated electrons and protons in aqueous solution, leading to the formation of nucleobase radical anions B˙, radical cations B˙+ and their major deprotonated radical forms B(–H)˙. We also examine the chemical repair reaction by thiols, B(–H)˙(aq)+RSH(aq)=B(aq)+RS˙(aq), where B=A,G,C,T. Our results for the chemical repair of B(–H)˙ suggest that a PT-ET pathway should be favored for A and C at any pH, whereas for G and T, a PT-ET pathway is preferred at acidic and near neutral pH, but in the pH range 9-11, the ET pathway would dominate.

Place, publisher, year, edition, pages
2004. Vol. 6, 2426-2433 p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-91638DOI: 10.1039/B400507DOAI: oai:DiVA.org:uu-91638DiVA: diva2:164437
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2013-05-16Bibliographically 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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