Quantitative determination of the selectivities of five different phenyl radicals in hydrogen atom abstraction from ethanol

Abstract

An experimental method is described for obtaining quantitative selectivity information for H-atom abstraction by organic radicals from different sites of a substrate in the gas phase. The method is used to determine the selectivities of five different phenyl radicals toward the three different types of hydrogen atoms in ethanol. This experimental method involves studying the reactivities and selectivities of derivatives of the radicals that contain a chemically inert, charged group (distonic ions), which allows them to be manipulated in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. A large number of studies suggest that the action of some potential anti-tumor antibiotics is based on H-atom abstraction by aromatic, ,-biradical intermediates from a sugar moiety in DNA (which ultimately leads to cell death) [1][2][3][4][5][6][7][8][9]. These compounds, however, are also destructive to healthy cells. An understanding of the factors that control the selectivity of aryl monoradicals and biradicals in H-atom abstraction reactions could aid the development of drugs that are more selective and, thus, less cytotoxic [10]. Here, we report the results for the first of a series of gas-phase studies on the selectivity of aryl radicals in H-atom abstraction reactions.An examination of H-versus D-atom abstraction from a partially labeled substrate by a phenyl radical yields semi-quantitative information about the selectivity of the radical. The difficulty, however, is that the selectivity observed in such reactions does not exactly correspond to the selectivity that is observed for the same site in an unlabeled compound. If a kinetic isotope effect (KIE) exists, the presence of a heavy isotope can affect the relative abundances of the products. That is, D-atom abstraction is likely to be slower, relative to H-atom abstraction, from the same site in the same molecule. Thus, in order to use the results obtained from selectivity studies of reactions of deuterium labeled compounds to understand the selectivities of the reactions of unlabeled analogs, it is necessary to develop a method that accounts for any potential KIE.Dunlop and Tully have previously reported a method for obtaining site-specific rate constants for H-atom abstraction by HO⅐ from 2-propanol in the gas phase by using a laser photolysis/laser-induced fluorescence technique [11]. However, this approach is based on the assumption that the KIE measured for HO⅐ for abstraction of a primary (methyl) H-/D-atom from ethane, or neopentane, represents the relative reactivity of HO⅐ toward CH 3 -and CD 3 -groups in 2-propanol. Herein, we report an approach that can be used to obtain quantitative selectivity information for radicals in H-atom abstraction reactions that involve partially deuterium-labeled substrates without the assumption made by Dunlop and Tully, and the application of this method for the determination of the selectivities of five substituted phenyl radicals toward the three different types of hydrogen atoms in ethanol. Our method is ...