Mechanism of Decomposition of the Human Defense Factor Hypothiocyanite Near Physiological pH

Abstract

Relatively little is known about the reaction chemistry of the human defense factor hypothiocyanite (OSCN(-)) and its conjugate acid hypothiocyanous acid (HOSCN), in part because of their instability in aqueous solutions. Herein we report that HOSCN/OSCN(-) can engage in a cascade of pH- and concentration-dependent comproportionation, disproportionation, and hydrolysis reactions that control its stability in water. On the basis of reaction kinetic, spectroscopic, and chromatographic methods, a detailed mechanism is proposed for the decomposition of HOSCN/OSCN(-) in the range of pH 4-7 to eventually give simple inorganic anions including CN(-), OCN(-), SCN(-), SO(3)(2-), and SO(4)(2-). Thiocyanogen ((SCN)(2)) is proposed to be a key intermediate in the hydrolysis; and the facile reaction of (SCN)(2) with OSCN(-) to give NCS(═O)SCN, a previously unknown reactive sulfur species, has been independently investigated. The mechanism of the aqueous decomposition of (SCN)(2) around pH 4 is also reported. The resulting mechanistic models for the decomposition of HOSCN and (SCN)(2) address previous empirical observations, including the facts that the presence of SCN(-) and/or (SCN)(2) decreases the stability of HOSCN/OSCN(-), that radioisotopic labeling provided evidence that under physiological conditions decomposing OSCN(-) is not in equilibrium with (SCN)(2) and SCN(-), and that the hydrolysis of (SCN)(2) near neutral pH does not produce OSCN(-). Accordingly, we demonstrate that, during the human peroxidase-catalyzed oxidation of SCN(-), (SCN)(2) cannot be the precursor of the OSCN(-) that is produced.

Hypothiocyanous Acid Suppresses PolyI:C-Induced Antiviral Responses by Modulating IRF3 Phosphorylation in Human Airway Epithelial Cells

“…In this pathway, IRF3 is activated by the linear ubiquitination of its lysine residues, which triggers its interaction with B-cell lymphoma 2-associated X protein (BAX), leading to mitochondrial activation and apoptosis (Chattopadhyay et al 2016). It has been reported that lysine residues can be carbamylated with cyanate (Wang et al 2007), a decomposition product of HOSCN (Kalmár et al 2011). Therefore, it is possible that HOSCN inhibits the interaction of IRF3 with BAX by blocking the ubiquitination of IRF3 lysine residues.…”

Tryptophan oxidation in proteins exposed to thiocyanate-derived oxidants

“…(SCN) 2 is produced through comproportionation reactions of HOSCN and SCN À [5]. Above pH 2, the comproportionation reaction is slow and intermediate (SCN) 2 reacts rapidly with HOSCN to give disproportionation products [38]. When the pH is above 2, based upon previous kinetic studies, we would expect the transient concentration of (SCN) 2 to be low, and (SCN) 2 would be too unstable (for example with respect to its reaction with HOSCN) to participate in Trp oxidation.…”

Anorganski spojevi sumpora u ljudskom tijelu. II. Tiocianati.

“…79,94,95 SPO je strukturno i katalitički slična laktoperoksidazi. 96 74,100 HOSCN je moćno mikrobicidno sredstvo koje ubija ili sprječava rast patogena: 70,79,80,85,86,101,102 raznih bakterija (uključujući i Heliobacter pylori), virusa koji se prenose oralnim putem (herpes simplex 1, respiratorni sincicijski virus, echovirus tip 11, HIV), nekih gljivica (primjerice, Candida albicans) i parazita (npr. Toxoplasma gondii).…”