Oxidation of the natural amino acids by a ferryl complex: Kinetic and mechanistic studies with peptide model compounds

Ahmed I. Abouelatta, Ashley A. Campanali, Anil R. Ekkati, Mark Shamoun, Suneth Kalapugama, Jeremy J. Kodanko

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29 Scopus citations

Abstract

Kinetic and mechanistic studies detailing the oxidation of substrates derived from the 20 natural amino acids by the ferryl complex [Fe IV(O)(N4Py)]2+ are described. Substrates of the general formula Ac-AA-NHtBu were treated with the ferryl complex under identical conditions ([Ac-AA-NHtBu] = 10 mM, [Fe] = 1 mM, 1:1 H2O/CH 3CN), and pseudo-first-order rate constants were obtained. Relative rate constants calculated from these data illustrated the five most reactive substrates; in order of decreasing reactivity were those derived from Cys, Tyr, Trp, Met, and Gly. Second-order rate constants were determined for these substrates by varying substrate concentration under pseudo-first-order conditions. Substrates derived from the other natural amino acids did not display significant reactivity, accelerating decomposition of the ferryl complex at a rate less than 10 times that of the control reaction with no substrate added. Ferryl decomposition rates changed in D2O/CD3CN for the Cys, Tyr, and Trp substrates, giving deuterium kinetic isotope effects of 4.3, 29, and 5.2, respectively, consistent with electron-transfer, proton-transfer (Cys and Trp), or hydrogen atom abstraction (Tyr) mechanisms. Decomposition rates for [FeIV(O)(N4Py)]2+ in the presence of the Met and Gly substrates were identical in H2O/CH3CN versus D2O/CD3CN solvents. A deuterium kinetic isotope effect of 4.8 was observed with the labeled substrate 2,2-d2-Ac-Gly- NHtBu, consistent with [FeIV(O)(N4Py)]2+ abstracting an α-hydrogen atom from Ac-Gly-NHtBu and generating a glycyl radical. Abstraction of α-hydrogen atoms from amino acid substrates other than Gly and oxidation of side chains contained in the amino acids other than Cys, Tyr, Trp, and Met were slow by comparison.

Original languageEnglish
Pages (from-to)7729-7739
Number of pages11
JournalInorganic Chemistry
Volume48
Issue number16
DOIs
StatePublished - Aug 17 2009

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