Peptide Peroxyl Radicals: Base-Induced O2*- Elimination versus Bimolecular Decay. A Pulse Radiolysis and Product Study

Article abstract of DOI:10.1021/j100117a026

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 and ca. 0.5 s^-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...