Reactivity and Selectivity of Charged Phenyl Radicals toward Amino Acids in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

Abstract

The reactivity of ten charged phenyl radicals toward several amino acids was examined in the gas phase in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. All radicals abstract a hydrogen atom from the amino acids, as expected. The most electrophilic radicals (with a greater calculated vertical electron affinity (EA) at the radical site) also react with these amino acids via NH2 abstraction (a nonradical nucleophilic addition-elimination reaction). Both the radical (hydrogen atom abstraction) and nonradical (NH2 abstraction) reaction efficiencies were found to increase with the electrophilicity (EA) of the radical. However, NH2 abstraction is more strongly influenced by EA. In contrast to an earlier report, the ionization energies of the amino acids do not appear to play a general reactivity controlling role. Studies using several partially deuterium-labeled amino acids revealed that abstraction of a hydrogen atom from the α-carbon is only preferred for glycine; for the other amino acids, a hydrogen atom is preferentially abstracted from the side chain. The electrophilicity of the radicals does not appear to have a major influence on the site from which the hydrogen atom is abstracted. Hence, the regioselectivity of hydrogen atom abstraction appears to be independent of the structure of the radical but dependent on the structure of the amino acid. Surprisingly, abstraction of two hydrogen atoms was observed for the 3-nitro-5-dehydrophenyl pyridinium radical, indicating that substituents on the radical not only influence the EA of the radical but also can be involved in the reaction. In disagreement with an earlier report, proline was found to display several unprecedented reaction pathways that likely do not proceed via a radical mechanism but rather by a nucleophilic addition-elimination mechanism. Both NH2 and 15NH2 groups were abstracted from lysine labeled with 15N on the side-chain, indicating that NH2 abstraction occurs both from the amino terminus as well as from the side-chain. Quantum chemical calculations were employed to obtain insights into some of the reaction mechanisms.

Chlorine substitution promotes phenyl radical loss from C8-phenoxy-2′-deoxyguanosine adducts: implications for biomarker identification from chlorophenol exposure

“…2(f)). The fragment peak at m/z 378 represents loss of the sugar moiety (116) followed by the neutral loss of HCl (36). This type of cleavage pattern was also observed for 2,4,6-TCP-O-dG (5) ( Fig.…”

“…Our calculations also demonstrate the destabilizing influence of 2‐Cl and 4‐Cl substituents, but suggest a slightly destabilizing influence by 3‐Cl atoms (Table ). The calculations (Table ) and experimental MS experiments demonstrate that homolytic bond cleavage of the O‐linked C8‐dG nucleoside adducts is not driven by stability of the phenyl radical product. This prediction is contrasted by fragmentation of the Bn‐O‐dG derivative ( 7 ) in which benzyl radical stability is expected to provide the driving force for production of the nucleoside distonic ion.…”

“…Substituent effects on phenyl radical stability have been studied in detail by the Kenttämaa laboratory using MS experiments. [35,36] These studies demonstrate that halogen substituents (F and Cl) increase the electron affinity (EA) of the phenyl radical, making it more electrophilic and more reactive toward H-atom abstraction processes. Cioslowski et al utilized DFT calculations to determine the impact of Cl-substitution on phenyl radical formation from polychlorinated benzenes.…”

Properties and Reactivity of Gaseous Distonic Radical Ions with Aryl Radical Sites

“…Numerous positively charged phenyl radicals were later allowed to react with several partially isotope labeled amino acids. 281 Results obtained for partially deuterium-labeled leucine and proline indicated that only a fraction of the hydrogen atom abstractions, if any, occurred at the α-carbon of the amino acid. Instead, the majority of hydrogen atoms are abstracted from the alkyl side chain.…”

White cheeses as a potential source of bioactive peptides

“…Also, antioxidant enzymes such as superoxide dismutase and peroxidase, can inhibit lipid oxidation by catalyzing the conversion of superoxide anion to hydrogen peroxide and the conversion of hydrogen peroxide to water, respectively (Valko et al, 2007). Besides, the selectivity of radical attacks on amino acid side chains and physical location the radical generation can be related to the energy of oxidation (Pates et al, 2011). Finally, heating proteins in the presence of sugars can form brown polymers called melanoidins or Maillard reaction products that act as antioxidants (Žilić et al, 2012).…”