One-electron reduction of N-chlorinated and N-brominated species is a source of radicals and bromine atom formation

David I. Pattison, Robert J. O'Reilly, Ojia Skaff, Leo Radom, Robert F. Anderson, Michael J. Davies

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (O2 •-) can reduce N-halogenated species to nitrogen- and carbon-centered radicals. N-Halogenated species and O2 •- 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 k2 > 109 M-1 s-1, whereas O2 •- 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.

Original languageEnglish
Pages (from-to)371-382
Number of pages12
JournalChemical Research in Toxicology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 21 2011
Externally publishedYes

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Bromine
Imides
Electron affinity
Electrons
Oxidants
Atoms
Chloramines
Nitrogen
Bromosuccinimide
Ions
Hypochlorous Acid
Biological Models
Nucleophiles
Immune system
Human Development
Substrates
Sulfur
Amides
Superoxides
Oxidation-Reduction

ASJC Scopus subject areas

  • Toxicology

Cite this

One-electron reduction of N-chlorinated and N-brominated species is a source of radicals and bromine atom formation. / Pattison, David I.; O'Reilly, Robert J.; Skaff, Ojia; Radom, Leo; Anderson, Robert F.; Davies, Michael J.

In: Chemical Research in Toxicology, Vol. 24, No. 3, 21.03.2011, p. 371-382.

Research output: Contribution to journalArticle

Pattison, David I. ; O'Reilly, Robert J. ; Skaff, Ojia ; Radom, Leo ; Anderson, Robert F. ; Davies, Michael J. / One-electron reduction of N-chlorinated and N-brominated species is a source of radicals and bromine atom formation. In: Chemical Research in Toxicology. 2011 ; Vol. 24, No. 3. pp. 371-382.
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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 (O2 •-) can reduce N-halogenated species to nitrogen- and carbon-centered radicals. N-Halogenated species and O2 •- 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 k2 > 109 M-1 s-1, whereas O2 •- 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•.",
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