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 ...

Direct Comparison of Solution and Gas-Phase Reactions of the Three Distonic Isomers of the Pyridine Radical Cation with Methanol

“…Previous studies of positively charged phenyl radicals in the gas phase have shown that the selectivity of hydrogen atom abstraction from ethanol is related to the EAs of the radicals. 47 Radicals with a lower EA (indicating lower reactivity) tend to attack the CH 2 -group rather than the CH 3 -group of ethanol because the CH 2 -group has a lower homolytic C-H bond dissociation energy. Indeed, in the gas phase, the hydrogen atom abstraction efficiency from methanol is 1.7 % and 0.4 % for the protonated 3- and 4-isomers, respectively.…”

Correlation of Hydrogen-Atom Abstraction Reaction Efficiencies for Aryl Radicals with their Vertical Electron Affinities and the Vertical Ionization Energies of the Hydrogen-Atom Donors

“…Because the ionic avoided curve crossing model (described above) predicts that the reaction efficiencies should also depend on the difference between the IE of the hydrogen-atom donor and the EA of the aryl radical (i.e., (IE – EA)), it was of interest to examine this relationship by using several different aryl radicals and hydrogen-atom donors. Thus, reaction efficiencies (measured here for cyclohexane and isopropanol, or measured previously) for hydrogenatom abstraction from ethanol by seven different aryl radicals ( g , k , l , n , q , s , t ),61,76 from tetrahydrofuran by twenty different aryl radicals ( b , c , d , e , f , g , h , i , j , l , m , q , s , t , aa , bb , cc , dd , ee , ff ),22,23,27,28,63 and from 2-methyltetrahydrofuran by eleven different aryl radicals ( b , d , e , f , h , i , j , m , s , aa , bb ),23 were studied. The calculated (IE – EA) values and the reaction efficiencies for hydrogen-atom abstraction are listed in Table 5.…”

Gas-Phase Reactivity of Protonated 2-, 3-, and 4-Dehydropyridine Radicals Toward Organic Reagents

“…However, the calculated reaction enthalpies (ΔH rxn ) associated with the hydrogen atom abstraction reactions of charged radicals 2 – 4 with methanol and ethanol (Table 3) do not reflect the observed differences in the reaction rates with these two neutral reagents. For example, ΔH rxn for hydrogen atom abstraction from the α-carbon in ethanol48 by 2 is only 0.2 and 3.3 kcal/mol more exothermic than those for 3 and 4 (ΔH rxn ; −25.6, −25.4 and −22.3 kcal/mol, respectively; Table 3), yet the reaction efficiency for hydrogen atom abstraction by 2 (33%; Table 1) differs from that of 3 (11%) by a factor of three and from that of 4 (4.2%) by a factor of about eight. Similar trends are also observed for methanol (Tables 1 and 3).…”