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

• Published in: Journal of the American Chemical Society 2011-12, Vol.133 (49), p.19911-19921
• Main Authors: Kalmár, József, Woldegiorgis, Kelemu L, Biri, Bernadett, Ashby, Michael T
• Format: Article
• Language: English
• Subjects: Anions - chemistry; Humans; Hydrogen-Ion Concentration; Hydrolysis; Spectrum Analysis; Thiocyanates - chemistry; Water - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja2083152

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–, SO3 2–, and SO4 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.