One-Electron Reduction of N-Chlorinated and N-Brominated Species Is a Source of Radicals and Bromine Atom Formation

Abstract

Hypochlorous (HOCl) and hypobromous (HOBr) acids are strong bactericidal oxidants that are generated by the human immune system but are implicated in the development of many human inflammatory diseases (e.g., atherosclerosis, asthma). These oxidants react readily with sulfur- and nitrogen-containing nucleophiles, with the latter generating N-halogenated species (e.g., chloramines/bromamines (RR'NX; X = Cl, Br)) as initial products. Redox-active metal ions and superoxide radicals (O(2)(•-)) can reduce N-halogenated species to nitrogen- and carbon-centered radicals. N-Halogenated species and O(2)(•-) are generated simultaneously at sites of inflammation, but the significance of their interactions remains unclear. In the present study, rate constants for the reduction of N-halogenated amines, amides, and imides to model potential biological substrates have been determined. Hydrated electrons reduce these species with k(2) > 10(9) M(-1) s(-1), whereas O(2)(•-) reduced only N-halogenated imides with complex kinetics indicative of chain reactions. For N-bromoimides, heterolytic cleavage of the N-Br bond yielded bromine atoms (Br(•)), whereas for other substrates, N-centered radicals and Cl(-)/Br(-) were produced. High-level quantum chemical procedures have been used to calculate gas-phase electron affinities and aqueous solution reduction potentials. The effects of substituents on the electron affinities of aminyl, amidyl, and imidyl radicals are rationalized on the basis of differential effects on the stabilities of the radicals and anions. The calculated reduction potentials are consistent with the experimental observations, with Br(•) production predicted for N-bromosuccinimide, while halide ion formation is predicted in all other cases. These data suggest that interaction of N-halogenated species with O(2)(•-) may produce deleterious N-centered radicals and Br(•).

Free radical studies of components of the extracellular matrix: contributions to protection of biomolecules and biomaterials from sterilising doses of ionising radiation

“…These findings suggested that these potential in vivo oxidizing radicals, particularly the carbonate radical, may react in a site-specific manner with the N-Cl group in the glycosaminoglycan chloramides. For the strongly-reducing species, formate radicals and hydrated electrons, the reactions with the chlroamidesare 100% site-specific, attacking only the N-Cl group and releasing chloride ion in 100% yield as confirmed in other pulse radiolysis studies on chloramines (Poskrebyshev et al 2003;Pattison et al 2002Pattison et al , 2011.…”

Decomposition of N-Chloroglycine in Alkaline Aqueous Solution: Kinetics and Mechanism

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] These reactions lead to the formation of various N-chlorinated amines under various conditions. 20,21 Hypochlorous acid is formed in vivo by the oxidation of chloride ion with hydrogen peroxide catalyzed by the myeloperoxidase enzyme.…”

One-electron oxidation and reduction of glycosaminoglycan chloramides: A kinetic study

“…Pulse radiolysis studies of the simplest chloramine, NH 2 Cl, showed that it reacts with the hydrated electron at diffusion-controlled rates (k= 2.2 x 10 10 M -1 s -1 ) [25,26]. In more recent pulse radiolysis studies of the chloramines and chloramides of amino acid derivatives [27] and of chloro-and bromo-derivatives of model compounds, such as Nbromoglutarimide (NBG) and N-bromosuccinimide (NBS) [28], hydrated electrons were also shown to react at near diffusion-controlled rates. In the latter study, superoxide radicals were also reacted with NBG and NBS and found to follow complex chain reaction pathways.…”