Fate of free radicals generated during one-electron reductions of 4-alkyl-1,4-peroxyquinols by cytochrome P-450

Journal Article · · Chem. Res. Toxicol.; (United States)

DOI:https://doi.org/10.1021/tx00006a010· OSTI ID:6201954

Yumibe, N P; Thompson, J A

Free radicals resulting from the one-electron reduction and subsequent homolytic cleavage of oxygen-oxygen bonds by heme proteins are likely to be responsible for some aspects of the toxicity of organic hydroperoxides. In the present work, effects of the 4-alkyl substituent of 2,6-di-tert-butyl-4-alkyl-4-hydroperoxycytohexa-2,5-dienones on radical production were investigated with microsomal cytochrome P-450 from rat liver. Quinoxy radicals from homolysis of the peroxyquinols underwent ..beta..-scission to produce a quinone and an alkyl radical, and this process occurred with increasing frequency as the stability of the alkyl radical increased. The fate of benzyl and 2-phenylethyl radicals generated from the appropriately substituted peroxyquinols was investigated also. The former was converted to benzyl alcohol, benzaldehyde, and toluene and the latter to 2-phenylethanol, phenylacetaldehyde, ethylbenzene, styrene, and benzaldehyde. Oxygen-18 labeling studies demonstrate that 80-85% of the benzyl alcohol incorporated oxygen from the hydroperoxide and the balance from molecular oxygen. This indicates that the predominant reaction pathway involved recombination between the benzyl radical and the iron-bound hydroxyl radical of the P-450 intermediate complex. By contrast, about 50% of 2-phenylethanol from the 2-phenylethyl radical incorporated oxygen from water and the balance from O/sub 2/. Two alternative mechanisms are proposed to explain the formation of 2-phenylethanol that contained oxygen from water and the concurrent formation of styrene: (a) oxygen exchange of the P-450 intermediate with water, followed by hydrogen abstraction and radical recombination reactions with the P-450 complex, or (b) oxidation of the radical to the 2-phenylethyl cation followed by proton elimination and hydration.

• Research Organization: Univ. of Colorado, Boulder (USA)
• OSTI ID: 6201954
• Journal Information: Chem. Res. Toxicol.; (United States), Vol. 1:6
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
HYDROGEN PEROXIDE
TOXICITY
OXINE
METABOLISM
RADICALS
BIOSYNTHESIS
CYTOCHROMES
LIVER
METABOLIC ACTIVATION
MICROSOMES
OXYGEN 18
RATS
TRACER TECHNIQUES
ANIMALS
AROMATICS
AZAARENES
AZINES
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
EVEN-EVEN NUCLEI
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
OXYGEN COMPOUNDS
OXYGEN ISOTOPES
PEROXIDES
PIGMENTS
PROTEINS
PYRIDINES
QUINOLINES
RODENTS
STABLE ISOTOPES
SYNTHESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques