Gas-phase ion-molecule reaction studies on DNA components by using laser -induced acoustic desorption (LIAD) coupled with FT -ICR mass spectrometry
Some anti-tumor antibiotics are believed to generate aromatic σ,σ-biradicals that attack DNA of cancer cells. However, little is known about the reactions of phenyl radicals with DNA. A better understanding of these reactions may facilitate the design of better drugs. This research focuses on the characterization of the factors that affect a phenyl radical's ability to attack DNA. Further, the thermochemical properties of nucleobase radical cations were examined. The experiments were carried out by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR) coupled with laser-induced acoustic desorption (LIAD). H-atom abstraction by the phenyl radicals (N-phenyl-3-dehydropyridinium (radical a), N-(3-dehydrophenyl)pyridinium (radical b) and N-methyl-2-dehydropyridinium (radical c)) with different electron affinities (EA, c > a > b) was found to be the predominant reaction for all tested nucleosides and dinucleoside phosphates. In addition, radical a attacks purine bases and radical c attacks nucleobases, with the exception of thymine, upon reactions with dinucleoside phosphates. An increase in the EA of a radical facilitates both the addition and H-atom abstraction reactions, but more the former. These results suggest that the less electrophilic phenyl radicals are more selective toward H-atom abstraction, while the more electrophilic phenyl radicals also cause substantial base damage. Purine bases are more vulnerable than pyrimidine bases toward radical damage. Finally, the recombination energies of the nucleobase radical cations were formed to be in agreement with the established trend in ionization potentials, U > T > C > A > G. The gas-phase acidity ordering of the nucleobase radical cations was found to be A+. (213 ± 3 kcal/mol) > T+. (195.5 ± 3 kcal/mol) > U+. (192 ± 3 kcal/mol) > C+. (189 ± 3 kcal/mol).
Kenttamaa, Purdue University.
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