Reactions of substituted phenyl radicals with organic compounds and nucleic acid components: A mass spectrometric study

Degradation of DNA via radical attack plays an important role in various biological processes (e.g., carcinogenesis). Radicals (e.g., aromatic sigma-radicals) can add to a double bond of a nucleobase or abstract a hydrogen atom from the sugar moiety, leading to DNA cleavage. Unfortunately, little is currently known about the factors (e.g., enthalpic, polar) that control the reactivity of these radical intermediates. This research focuses on the structural features that affect a phenyl radical's ability to attack DNA.;The powerful tool of Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR) was employed in studies of the intrinsic reactivity of phenyl radicals. The experimental approach is based on the placement of a chemically inert charged group that allows manipulation of the radicals in the mass spectrometer. Addition of neutral groups in the phenyl ring allows the evaluation of substituent effects in the gas phase. This approach was employed to demonstrate that the addition of electron-withdrawing groups to the phenyl ring enhances its reactivity toward several organic compounds and components of DNA. The increases in reactions rates were found not to be due to changes in the heats of reaction, but rather attributable to polar effects.;The ultimate goal of this research is to examine reactions of polyatomic radicals with oligonucleotides. However, these biomolecules are nonvolatile species that decompose upon heating. As a result, a laser desorption approach involving optoacoustic waves was developed to evaporate these fragile biological substrates. The evaporation and ionization of various nucleosides was achieved with this Laser Induced Acoustic Desorption (LIAD) method. Finally, LIAD was shown to be a practical method for the examination of radical reactions of laser-desorbed biomolecules, such as thymidine.