59417-41-3Relevant articles and documents
Peptide Peroxyl Radicals: Base-Induced O2*- Elimination versus Bimolecular Decay. A Pulse Radiolysis and Product Study
Mieden, Oliver J.,Schuchmann, Man Nien,Sonntag, Clemens von
, p. 3783 - 3790 (2007/10/02)
Radiolytically generated OH radicals react with the cyclic dipeptides glycine anhydride (1) and alanine anhydride (2), forming a single type of peptide radical in each case by abstracting a carbon-bound H atom at the ring.In the case of sarcosine anhydride (3), besides the C(3) or C(6) atoms (78percent), the H atoms at the N-methyl groups are also targets of the OH radical attack (22percent).In N2O/O2 (4:1 v/v) saturated solutions these peptide radicals add oxygen (k ca. 2*109 dm3 mol-1 s-1) to form the corresponding peroxyl radicals 6 (from 1), 7 (from 2), and 12 and 13 (from 3).The kinetics of O2*- elimination from the radicals 6 and 7 has been monitored by pulse radiolysis techniques.The pKa values of the peroxyl radicals 6 and 7 have been determined to be 10.8 and 11.2, respectively.The anions of these peroxyl radicals (6a and 7a) rapidly eliminate O2*- with the rate constants 1.6*105 and 3.7*106 s-1, respectively.In contrast, the spontaneous HO2* elimination reactions of the peroxyl radicals 6 and 7 are very slow, with rate constants of -1 as estimated from product analysis.The overall bimolecular decay rate constants of the cyclic dipeptide peroxyl radicals have been determined by pulse radiolysis measurements (2k(6) = 8.6*108 dm3 mol-1 s-1; 2k (7) = 1.6*108 dm3 mol-1 s-1; 2k(12/13) = 4.0*108 dm3 mol-1 s-1).The main products (G values) in the γ radiolysis of glycine anhydride in N2O/O2-saturated solution at pH 6 are 3-hydroxy-2,5-dioxopiperazine (14) (3.5*10-7 mol J-1), 2,3,5-trioxopiperazine (17) (1.6*10-7 mol J-1), and 2,5-dioxo-2,3,4,5-tetrahydropyrazine (8) (0.4*10-7 mol J-1).The product 8 is in equilibrium with its hydrate 14, which is again in equilibrium with its ring-opened form N-glyoxylyl glycinamide (16).In acidic solutions radical 6 decays essentially bimolecularly, giving equal amounts of 14 (present in an equilibrium mixture of 8, 14, and 16) and 17.In basic solution 14 becomes the single main product as the OH(-) -induced O2*- elimination reaction becomes much faster than the bimolecular decay.This is in good agreement with the yield of O2*- formation as monitored by its reaction with tetranitromethane under various pH conditions.With alanine anhydride (2), the main reaction under γ radiolysis conditions even at pH 6 is still the OH(-) -induced O2*- elimination reaction with 3-hydroxy-2,5-dioxo-3,6-dimethylpiperazine (15) as the single main product (G(15) = 4.7*10-7 mol J-1.The major peroxyl radical in sarcosine anhydride system (12) only decays bimolecularly either by self-termination or by cross-termination with the minor peroxy radical (13) (products at pH 6 in γ radiolysis: 2,3,5-trioxo-1,4-dimethylpiperazine (20), G = 4.0*10-7 mol J-1; 3-hydroxy-2,5-dioxo-1,4-dimethylpiperazine (21), G = 0.4*10-7 mol J-1; 1-formyl-2,5-dioxo-4-methylpiperazine (22), G = 0.6*10-7 mol J-1; and 2,5-dioxo-1-methylpiperazine (24), G = 0.6...
Peptide Free-Radicals: The Reactions of OH Radicals with Glycine Anhydride and its Methyl Derivatives Sarcosine and Alanine Anhydride. A Pulse Radiolysis and Product Study
Mieden, Oliver J.,Sonntag, Clemens von
, p. 959 - 974 (2007/10/02)
The reactions of radiolytically generated OH radicals and H atoms with the cyclic dipeptides of glycine, alanine and sarcosine in deoxygenated aqueous solutions and the subsequent reactions of the transient peptide radicals were studied in the absence and presence of K3Fe(CN)6 as oxidant by pulse radiolysis and product analysis.Hydroxyl radicals and H atoms react with glycine anhydride and alanine anhydride by abstracting an H atom bound at C-3; there is no evidence for any other site of attack at these two peptides.The resulting radicals have pKa values of 9.8 and 10.6, respectively.In the absence of an oxidant the radicals decay by second order (2k = 7.0*108 dm3 mol-1s-1 and 2k = 4.4*108 dm3 mol-1 s-1, resp.), the main fraction (94percent of the glycine anhydride-derived radicals, 90percent of the alanine anhydride-derived radicals)yielding dehydrodimers (G = 0.58 μmolJ-1 and 0.56 μmolJ-1 (in monomer units), resp.A small portion however disproportionates via abstraction of a C-6-bound H atom followed by isomerization to 2,5-dihydroxypyrazines (pKa values of the parent 2.5-dihydroxypyrazine at about 7.9 and 10.1) and subsequent addition of water to 2.5-diketo-3-hydroxypiperazines, thus indicating that the transfer of a carbon-bound hydrogen atom is prefered to the transfer of a nitrogen-bound hydrogen atom.No disproportionation products but three different dehydrodimers (G = 0.36, 0.18 and 0.04 μmol J-1 (in monomer units) were found after irradiation of sarcosine anhydride.In this case a dose rate and solute concentration dependence of dehydrodimer formation indicates a radical-solute reaction converting part of the N-methyl radicals (21percent of 'initial' attack) into the C-3-yl radicals.A rate constant of k = 600 +/- 50 dm3 mol-1 s-1 was obtained for this reaction by measuring and computing the dehydrodimer yields as a function of dose rate and solute concentration.Thus the observed transient spectrum account only for about 79percent of the radicals from the 'inital' attack at C-3.The rate of oxidation of the glycine anhydride-derived radicals by Fe(CN)63- reflects the pKa of the transient radical.The rate constant for oxidation of the (protonated) radical derived from glycine anhydride is k = 1.0*108 dm3 mol-1 s-1, the corresponding radical anion is oxidized with k = 3.1*108 dm3 mol-1 s-1.No change with pH was observed in the case of the alanine anhydridederived radicals (k = 7.9*108 dm3 mol-1 s-1).In contrast to the disproportion, oxidation by Fe(CN)63- leads to the removal of a proton from the heteroatom, a carbocation being the intermediate.The resulting dehydropiperazines rapidly add water to yield the corresponding 2.5-diketo-3-hydroxypiperazines (G = 0.61 μmol J-1 after oxidation of the glycine anhydride-derived radicals, G = 0.58 μmol J-1 after oxidation of the ... - Keywords: Glycine Anhydride, Alanine Anhydride, Sarcosine Anhydride, Pulse Radiolysis, Hydroxyl Radical, Peptide Radicals
