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^–, 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