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Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study

Abstract

The semi-iminoquinone radical of acetaminophen, which has previously been proposed as a possible hepatotoxic intermediate in the cytochrome P-450 catalysed oxidation of acetaminophen, has been generated and studied by pulse radiolysis. In the absence of other reactive solutes, the radical decays rapidly by second order kinetics with a rate constant (2k/sub 2/) of (2.2 +- 0.4) x 10/sup 9/ M/sup -1/ sec/sup -1/. In alkaline solutions the radical deprotonates with a pK of 11.1 +- 0.1 to form a radical-anion. The acetaminophen radical-anion reacts with resorcinol at high pH values, leading to the formation of a transient equilibrium from which the one-electron reduction potential of the semi-iminoquinone radical of acetaminophen is estimated to be + 0.707 +- 0.01 V at pH 7. This value predicts that acetaminophen should be oxidised by thiyl radicals. This was confirmed by pulse radiolysis experiments for reaction of the cysteinyl radical, for which rate constants of 7 x 10/sup 6/ M/sup -1/ sec/sup -1/ at pH7 and 2.7 x 10/sup 8/ M/sup -1/ sec/sup -1/ at pH 11.3 were obtained. The reaction of O/sub 2/ with the acetaminophen semi-iminoquinone radical could not be detected by pulse radiolysis, and alternative mechanisms for superoxide radical formation are  More>>
Publication Date:
Jul 15, 1988
Product Type:
Journal Article
Reference Number:
AIX-20-011021; EDB-89-021405
Resource Relation:
Journal Name: Biochem. Pharmacol.; (United Kingdom); Journal Volume: 37:pt.14
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; ANALGESICS; RADICALS; RADIOLYSIS; ABSORPTION SPECTRA; CHEMICAL REACTION KINETICS; OXIDATION; CENTRAL NERVOUS SYSTEM DEPRESSANTS; CHEMICAL RADIATION EFFECTS; CHEMICAL REACTIONS; CHEMISTRY; DECOMPOSITION; DRUGS; KINETICS; RADIATION CHEMISTRY; RADIATION EFFECTS; REACTION KINETICS; SPECTRA; 400600* - Radiation Chemistry
OSTI ID:
6565484
Research Organizations:
Salford Univ. (UK). Dept. of Biological Sciences
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: CODEN: BCPCA
Submitting Site:
INIS
Size:
Pages: 2731-2738
Announcement Date:
Nov 15, 1988

Citation Formats

Bisby, R H, and Tabassum, N. Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study. United Kingdom: N. p., 1988. Web. doi:10.1016/0006-2952(88)90035-4.
Bisby, R H, & Tabassum, N. Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study. United Kingdom. doi:10.1016/0006-2952(88)90035-4.
Bisby, R H, and Tabassum, N. 1988. "Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study." United Kingdom. doi:10.1016/0006-2952(88)90035-4. https://www.osti.gov/servlets/purl/10.1016/0006-2952(88)90035-4.
@misc{etde_6565484,
title = {Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study}
author = {Bisby, R H, and Tabassum, N}
abstractNote = {The semi-iminoquinone radical of acetaminophen, which has previously been proposed as a possible hepatotoxic intermediate in the cytochrome P-450 catalysed oxidation of acetaminophen, has been generated and studied by pulse radiolysis. In the absence of other reactive solutes, the radical decays rapidly by second order kinetics with a rate constant (2k/sub 2/) of (2.2 +- 0.4) x 10/sup 9/ M/sup -1/ sec/sup -1/. In alkaline solutions the radical deprotonates with a pK of 11.1 +- 0.1 to form a radical-anion. The acetaminophen radical-anion reacts with resorcinol at high pH values, leading to the formation of a transient equilibrium from which the one-electron reduction potential of the semi-iminoquinone radical of acetaminophen is estimated to be + 0.707 +- 0.01 V at pH 7. This value predicts that acetaminophen should be oxidised by thiyl radicals. This was confirmed by pulse radiolysis experiments for reaction of the cysteinyl radical, for which rate constants of 7 x 10/sup 6/ M/sup -1/ sec/sup -1/ at pH7 and 2.7 x 10/sup 8/ M/sup -1/ sec/sup -1/ at pH 11.3 were obtained. The reaction of O/sub 2/ with the acetaminophen semi-iminoquinone radical could not be detected by pulse radiolysis, and alternative mechanisms for superoxide radical formation are discussed.}
doi = {10.1016/0006-2952(88)90035-4}
journal = {Biochem. Pharmacol.; (United Kingdom)}
volume = {37:pt.14}
journal type = {AC}
place = {United Kingdom}
year = {1988}
month = {Jul}
}