Oxyhalogen–Sulfur Chemistry: Kinetics and Mechanism of Oxidation of N-Acetyl-ʟ-methionine by Aqueous Iodine and Acidified Iodate

Abstract

The use of N-acetyl-l-methionine (NAM) as a bio-available source for methionine supplementation as well as its ability to reduce the toxicity of acetaminophen poisoning has been reported. Its interaction with the complex physiological matrix, however, has not been thoroughly investigated. This manuscript reports on the kinetics and mechanism of oxidation of NAM by acidic iodate and aqueous iodine. Oxidation of NAM proceeds by a two electron transfer process resulting in formation of a sole product: N-acetyl-l-methionine sulfoxide (NAMS=O). Data from electrospray ionization mass spectrometry confirmed the product of oxidation as NAMS=O. The stoichiometry of the reaction was deduced to be IO3– + 3NAM → I– + 3NAMS=O. In excess iodate, the stoichiometry was deduced to be 2IO3– + 5NAM + 2H+ → I2 + 5NAMS=O + H2O. The reaction between aqueous iodine and NAM gave a 1 : 1 stoichiometric ratio: NAM + I2 + H2O → NAMS=O + 2I– + H+. This reaction was relatively rapid when compared with that between NAM and iodate. It did, however, exhibit some auto-inhibitory effects through the formation of triiodide (I3–) which is a relatively inert electrophile when compared with aqueous iodine. A simple mechanism containing 11 reactions gave a reasonably good fit to the experimental data.

Electrochemistry-coupled to mass spectrometry in simulation of metabolic oxidation of methimazole: Identification and characterization of metabolites

“…Our research in the past has focused on investigating the mechanism of S-oxidation of organosulfur compounds. 9,10 Extensive studies from our laboratory have shown that nearly every organic sulfur compound presents a unique reactivity and no generic oxidation pathway can be easily derived. Sulfur atom has been implicated as a site of bioactivation, resulting in formation of reactive and potentially toxic metabolites from bioactivation of sulfur containing drugs.…”

Comment on the Principle of Detailed Balancing in Complex Mechanisms and Its Application to Iodate Reactions

“…Specifically, we identify a series of eight publications on iodate (IO 3 – ) reactions in aqueous solution having multistep mechanisms with a subset of three iodine-based reactions that violates the principle of detailed balancing. These publications describe oxidations by iodate of N -acetyl- l -methionine, N -acetylhomocysteine thiolactone (NAHT), methionine, cysteamine, N , N ′-dimethyl­amino­imino­methane­sulfinic acid, amidinothiourea, 2-aminoethanethiol sulfuric acid, and aminoiminomethanesulfinic acid (AIMSA) . Here, a mechanistic alternative is proposed that complies with detailed balancing.…”

“…Four − of the eight publications cited above all use the same set of rate constants for reactions , , and : k 1 = 2.8 M –3 s –1 , k –1 = 1.44 × 10 3 M –1 s –1 , k 2 = 2.1 × 10 8 M –2 s –1 , k –2 = 90 M –1 s –1 , k 3 = 8.6 × 10 2 M –2 s –1 , and k –3 = 2.00 M –1 s –1 . Thus, we obtain k 1 / k –1 = 1.9 × 10 –3 M –2 and ( k 2 / k –2 )­( k 3 / k –3 ) = 1.0 × 10 9 M –2 .…”