Gas -phase reactivity of aromatic σ,σ-biradicals toward DNA components in a Fourier-transform ion cyclotron resonance (FT -ICR) mass spectrometer

Linan Yang, Purdue University

Abstract

Aromatic σ,σ-biradicals with a 1,4-relationship between the radical sites are the reactive intermediates of the enediyne class of nonhydrolytic DNA cleavers. Molecular level knowledge of the key process, the reactions of the σ,σ-biradical intermediates with DNA, is needed to facilitate the rational design of more selective synthetic DNA-cleaving agents. My research involves the systematic investigation of the reactivity of aromatic σ,σ-biradicals toward DNA components in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. Studies on the gas-phase reactivity of selected σ,σ-biradicals toward small DNA components, such as sugars and nucleobases, demonstrate that the structure of a σ,σ-biradical has a major effect on its reactivity. Singlet-triplet gap (S-T gap) and electron affinity (EA) are two important factors that control the reactivity of these singlet biradicals. In addition to the S-T gap and EA, the dehydrocarbon atom separation in meta-benzyne type biradicals can be equally important. Laser-induced acoustic desorption (LIAD) can be used to evaporate thermally labile biomolecules into the gas phase as intact neutral molecules. This technique allows us to extend our biradical studies to nucleosides and dinucleoside phosphates. The results demonstrate that σ,σ-biradicals damage nucleosides and dinucleoside phosphates predominantly via nucleobase abstraction, as opposed to monoradicals that undergo predominant hydrogen atom abstraction. The results also demonstrate that the structure of the dinucleoside phosphate has a strong influence on its reactions with biradicals. Thymine was found to be the base least susceptible to (bi)radical attack, presumably due to its high ionization energy.

Degree

Ph.D.

Advisors

Kenttamaa, Purdue University.

Subject Area

Analytical chemistry

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