Oxidation of the Natural Amino Acids by a Ferryl Complex: Kinetic and Mechanistic Studies with Peptide Model Compounds

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 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.

Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H2O2 catalyzed by a nonheme imine based iron complex

“…3e On the other hand, no products have been observed in the oxidation of amino acids Ala, Val, Leu with KHSO 5 promoted by the pentadentate nonheme complex [Fe II (N4Py)] 2+ with the active species iron(IV)-oxo complex [Fe IV (O)(N4Py)] 2+ decaying at a rate faster than the hydrogen abstraction from these substrates. 15 The selectivity pattern observed with the 1/H 2 O 2 system resembles that of the cumyloxyl radical (CumOc) where exclusive HAT from a-C-H bond with Ala and a competition between side-chain vs. Ca-H bond cleavage for N-AcLeuOMe (4) were observed. 16 However, no HAT reaction from the tertiary b-C-H bond of N-AcValOMe (3) has been observed with CumOc, thus indicating that our system is less sensitive to steric effects in the HAT process.…”

“…For instance, [Fe IV (O)(N4Py)] 2+ reacts much faster with the electron-rich phenol moiety of N-AcTyrNHtBu than with the aromatic ring of N-AcPheNHtBu. 15 In view of the relevance of the Phe to Tyr transformation, reaction conditions were subsequently screened varying the amounts of catalyst and oxidant in order to optimize the Tyr yields. The results are shown in Table 2.…”

Site-Selective Peptide/Protein Cleavage

“…KHSO 5 as an oxidant through pattern b) in Fig 19 (Fig. 20) [158,159]. Oxidation of Ac-Xaa-NH t Bu, where Xaa ¼ Gly, produced N-acetylformamide as the major product through Cα-C (O) bond cleavage.…”

Green Polymer Synthesis: An Overview on Use of Microwave‐Irradiation

“…Amino acid amides effectively reacted to produce polypeptides in response to microwave heating. Highly enhanced coupling efficiency in solidphase peptide synthesis by microwave irradiation has motivated scientists to apply this procedure to the synthesis of key polypeptides [241][242][243][244][245][246]. In general, microwave-assisted reactions are faster than the conventional synthetic method due to the ability of MWs to disrupt the inter-and intra-chain bonds.…”