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Radiation-Induced Damage in Serine PhosphateInsights into a Mechanism for Direct DNA Strand Breakage

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journal contribution
posted on 10.06.2004, 00:00 by Jan Lipfert, Jorge Llano, Leif A. Eriksson
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.