Oxidation of the natural amino acids by a ferryl complex: kinetic and mechanistic studies with peptide model compounds.
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 H(2)O/CH(3)CN), 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 D(2)O/CD(3)CN 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 [Fe(IV)(O)(N4Py)](2+) in the presence of the Met and Gly substrates were identical in H(2)O/CH(3)CN versus D(2)O/CD(3)CN solvents. A deuterium kinetic isotope effect of 4.8 was observed with the labeled substrate 2,2-d(2)-Ac-Gly-NHtBu, consistent with [Fe(IV)(O)(N4Py)](2+) abstracting an alpha-hydrogen atom from Ac-Gly-NHtBu and generating a glycyl radical. Abstraction of alpha-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.
Abouelatta
Ahmed I
AI
Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, Michigan 48202, USA.
Campanali
Ashley A
AA
Ekkati
Anil R
AR
Shamoun
Mark
M
Kalapugama
Suneth
S
Kodanko
Jeremy J
JJ
D000596:Amino Acids / Q000737:chemistry*; D024361:Amino Acids, Basic / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*
D000596:Amino Acids; D024361:Amino Acids, Basic; D009942:Organometallic Compounds; D010455:Peptides; C066317:ferryl iron; D007501:Iron