Small Molecular, Macromolecular, and Cellular Chloramines React with Thiocyanate To Give the Human Defense Factor Hypothiocyanite

Abstract

Thiocyanate reacts non-catalytically with myeloperoxidase-derived HOCl to produce hypothiocyanite (OSCN−), thereby potentially limiting the propensity of HOCl to inflict host tissue damage that can lead to inflammatory diseases. However, the efficiency with which SCN− captures HOCl in vivo depends on the concentration of SCN− relative to other chemical targets. In blood plasma, where the concentration of SCN− is relatively low, proteins may be the principal initial targets of HOCl, and chloramines are a significant product. Chloramines eventually decompose to irreversibly damage proteins. In the present study, we demonstrate that SCN− reacts efficiently with chloramines in small molecules, in proteins, and in Escherichia coli cells to give OSCN− and the parent amine. Remarkably, OSCN− reacts faster than SCN− with chloramines. These reactions of SCN− and OSCN− with chloramines may repair some of the damage that is inflicted on protein amines by HOCl. Our observations are further evidence for the importance of secondary reactions during the redox cascades that are associated with oxidative stress by hypohalous acids.

Sarcoendoplasmic Reticulum Ca2+ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

“…Moreover, HOSCN can react with chloramines, longer-lived reaction products, and restore them to amines (42). It is also conceivable that Cl 2 produces chloramines in SERCA that are then repaired by HOSCN (43). However, our findings contrast with those in which SCN-induced decreases in SERCA activity were described (8).…”

Selective Metabolism of Hypothiocyanous Acid by Mammalian Thioredoxin Reductase Promotes Lung Innate Immunity and Antioxidant Defense

“…However, SCN, which is enriched in secretions, can effectively compete with Cl Ϫ for MPO and diminishes HOCl formation in favor of HOSCN (3). SCN also reacts directly with HOCl to form HOSCN (16), which alleviates cytotoxicity (17), and scavenges toxic metabolites of HOCl such as monochloramines, also forming HOSCN (16). Although HOSCN and HOCl both function in host defense, only HOSCN is well tolerated by mammalian tissue.…”

“…Although HOSCN is strongly acidic and reacts exclusively with thiolates and selenolates in biologic systems, HOCl is a milder acid with greater reduction potential (pK a ϭ 7.53, EЈ°p H 7 ϭ ϩ1280 mV for HOCl versus pK a ϭ 4.85, EЈ°p H 7 ϭ ϩ560 mV for HOSCN (35)) that reacts rapidly with thiols, selenols, amines (16), and phenyl rings (36) and can also undergo Fenton chemistry with the potential to generate hydroxyl radicals (13). Further, we observed no direct NADPH oxidation by HOSCN but did observe this feature in HOCl.…”

Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in human health

“…The favorable interaction of SCN − with compound I of MPO and EPO [8,9] protects cells by generating a weaker, less reactive oxidant in place of HOX (i.e., HOSCN, pK a =4.85, E’°=+560 mV; HOCl, pK a =7.53, E’°=+1280 mV; HOBr, pK a =8.8, E’°=+1130 mV [20,80]) (Figure 4). In addition to scavenging HOCl and HOBr, SCN − also reduces chloramines, a range of amino acid metabolites generated by HOCl [69,70,129]. Surprisingly, HOSCN may also reduce some chloramines [129].…”