Electrochemical oxidation of acetaminophen in aqueous solutions: Kinetic evaluation of hydrolysis, hydroxylation and dimerization processes

Abstract Electrochemical oxidation of acetaminophen (paracetamol) has been studied in various pHs using cyclic voltammetry and controlled-potential coulometry. The results indicate that electrochemically generated N -acetyl- p -benzoquinone-imine (NAPQI) participates in different type reactions based on solution's pH. It is hydrolyzed in strong acidic media and hydroxylated in strong alkaline media and also, it is dimerized in intermediate pHs. Furthermore, in this work, a simple method for electrochemical synthesis of acetaminophen's dimer is described. In addition, in various pHs, based on related mechanism, the observed homogeneous rate constants ( k obs ) of hydrolysis, hydroxylation and dimerization reactions were estimated by comparing the experimental cyclic voltammetric responses with the digital-simulated results. The most amounts of k obs are calculated in pHs less than 2 and more than 9. In this study, the least observed homogeneous rate constant ( k obs ) belongs to pHs 5.0 and 9.0.

[1]  R. Adams,et al.  Anodic oxidation pathways of phenolic compounds , 1972 .

[2]  D. Nematollahi,et al.  Investigation of electrochemically induced conjugate addition reaction: A facile approach to preparation of Schonberg adduct , 2008 .

[3]  D. Nematollahi,et al.  Estimation of homogeneous rate constants of reaction of electrochemically generated ortho‐benzoquinones with 1,3‐indandione , 2007 .

[4]  E. Valero,et al.  Quantification of acetaminophen by oxidation with tyrosinase in the presence of Besthorn's hydrazone. , 2003, Analytical biochemistry.

[5]  E. Valero,et al.  Catalytic oxidation of acetaminophen by tyrosinase in the presence of L-proline: a kinetic study. , 2003, Archives of biochemistry and biophysics.

[6]  D. Gunnell,et al.  Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. , 2000, Suicide & life-threatening behavior.

[7]  Kosuke Izutsu.  Electrochemistry in Nonaqueous Solutions , 2002 .

[8]  D. Nematollahi,et al.  Electroorganic synthesis of catecholthioethers. , 2005, The Journal of organic chemistry.

[9]  J. Rice,et al.  Voltammetry of acetaminophen and its metabolites , 1981 .

[10]  E. Hazai,et al.  Reduction of toxic metabolite formation of acetaminophen. , 2002, Biochemical and biophysical research communications.

[11]  A. Samadi-Maybodi,et al.  Mechanistic study of electrochemical oxidation of 4-tert-butylcatechol: A facile electrochemical method for the synthesis of new trimer of 4-tert-butylcatechol , 2004 .

[12]  A. Rettie,et al.  Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen. , 2000, Drug metabolism and disposition: the biological fate of chemicals.

[13]  A. Forbes,et al.  Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. , 1991, BMJ.

[14]  A. Y. Lu,et al.  N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Ebadi.  Electrocatalytic oxidation of hydroxylamine by (RuPc)2 graphite modified electrode , 2003 .

[16]  N. Tietz,et al.  Textbook of clinical chemistry , 1986 .

[17]  P. Dargan,et al.  Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism? , 2002, Drug safety.

[18]  R. Greef,et al.  Instrumental Methods in Electrochemistry , 2002 .

[19]  D. Miller,et al.  Identification of acetaminophen polymerization products catalyzed by horseradish peroxidase. , 1985, The Journal of biological chemistry.

[20]  M. Hulbert,et al.  Melanin. I. Kinetics of the oxidative cyclization of dopa to dopachrome. , 1974, The Journal of organic chemistry.

[21]  M. Heravi,et al.  Estimation of heterogeneous rate constants of reaction of electrochemically generated o-benzoquinones with various nucleophiles containing thiol group , 2009 .

[22]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .

[23]  Orawon Chailapakul,et al.  Electrochemical analysis of acetaminophen using a boron-doped diamond thin film electrode applied to flow injection system. , 2002, Journal of pharmaceutical and biomedical analysis.

[24]  Manfred Rudolph.  Digital simulations on unequally spaced grids.: Part 1. Critical remarks on using the point method by discretisation on a transformed grid , 2002 .

[25]  R. Mason,et al.  Free-radical metabolites of acetaminophen and a dimethylated derivative. , 1985, Environmental health perspectives.

[26]  D. Nematollahi,et al.  Electrosynthesis of symmetric and highly conjugated benzofuran via a unique ECECCC electrochemical mechanism: evidence for predominance of electrochemical oxidation versus intramolecular cyclization. , 2007, The Journal of organic chemistry.

[27]  S. Dehdashtian,et al.  A facile galvanostatic method for the synthesis of quinoxalinediones , 2006 .

[28]  R. Adams,et al.  Anodic hydroxylation of aromatic compounds , 1968 .

[29]  W. Trager,et al.  Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. , 1998, Chemical research in toxicology.

[30]  A. Proudfoot,et al.  Paracetamol (acetaminophen) poisoning , 1995, The Lancet.

[31]  M. Rafiee,et al.  Kinetic study of the oxidation of some catecholamines by digital simulation of cyclic voltammograms , 2005 .

[32]  R Williams,et al.  Early indicators of prognosis in fulminant hepatic failure. , 1989, Gastroenterology.