uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Radiation Induced Damage in Serine Phosphate: Insights into a Mechanism for Direct DNA Strand Breakage
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: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 108, no 23, 8036-8042 p.Article in journal (Refereed) Published
Abstract [en]

The radiation-induced decomposition mechanisms of l-O-serine phosphate and the properties of the resulting radicals are explored at the hybrid Hartree−Fock−density functional theory level B3LYP, incorporating a polarized continuum model (IEF-PCM). Three different radical products were identified in earlier experimental studies, formed through deamination (radical I), decarboxylation plus radical exchange (radical II), or dephosphorylation (radical III) reactions, respectively. The calculated hyperfine coupling constants of the resulting radicals agree well with experimental data. The computed energetics for the two competing mechanisms resulting from electron capture, radicals I and III, show that the deamination reaction is barrierless, whereas the dephosphorylation reaction requires an initial electronic redistribution and formation of a phosphoranyl radical with trigonal bipyramidal geometry. From this, the dephosphorylation reaction has to overcome a barrier of approximately 26 kcal/mol, which explains the predominance of radical I over radical III in the experimental measurements. For radical II, the initial decarboxylation step resulting from electron loss was explored and found to proceed without barriers. The results of the current study have implications for radiation-induced damage of amino acids. In addition, serine phosphate is a model of a DNA sugar−phosphate fragment, and thus we may obtain new insights into a possible mechanism for cleavage of the phosphate ester bond of the DNA backbone leading to strand break.

Place, publisher, year, edition, pages
2004. Vol. 108, no 23, 8036-8042 p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-91641DOI: 10.1021/jp037499eOAI: oai:DiVA.org:uu-91641DiVA: diva2:164440
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

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Quantum ChemistryDepartment of Cell and Molecular Biology
In the same journal
Journal of Physical Chemistry B
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 210 hits
ReferencesLink to record
Permanent link

Direct link