Gas-phase studies on the reactivity of charged, aromatic σ-radicals and differentiation of stereoisomers in a Fourier transform ion cyclotron resonance mass spectrometer
Abstract
Radical-induced DNA degradation plays an important role in the action of many anti-tumor drugs. Radicals can abstract a hydrogen atom from a sugar moiety in DNA, leading to DNA cleavage. However, little is known about the factors (e.g., enthalpic, polar) that control the reactivity of these radical intermediates. This research explores the structure/reactivity relationships by aromatic a-radicals that control the efficiency of hydrogen atom abstraction from neutral atom donors. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR) was employed to characterize the reactivity of aromatic σ-radicals. These radicals contain an electron withdrawing protonated or charged nitrogen atom that allows for mass spectrometric manipulation of the radicals. In addition, by variation of the position of the heteroatom, the rates of hydrogen atom abstraction were shown to be due to polar effects and not to changes in reaction exothermicities. Furthermore, the reactivity of aromatic σ,σ-radicals was shown to be controlled by both the magnitude of their singlet-triplet gap and polar effects. Development of methods to differentiate stereoisomeric compounds is an important area of research because simple and rapid methods are needed for the analysis of stereoisomeric pharmaceutical compounds. This thesis demonstrates that phosphenium ions can be used to rapidly differentiate certain diastereomeric hydroxysteroids in an FT-ICR. Reaction of the phosphenium ions with certain steroids gives rise to the formation of unique reaction products for only one of the isomers of a diastereomeric pair.
Degree
Ph.D.
Advisors
Kenttamaa, Purdue University.
Subject Area
Analytical chemistry
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