Mustard sulphoxide

Figure 2.1 Metabolic breakdown of SM. Proposed metabolic fate of SM (adapted from Black et alX). Metabolites are 1 SM 2 thiodiglycol 3 thiodi-glycol sulphoxide 4 mustard sulphoxide 5 mono-GSH-SM adduct 6 l-[S-(iV-acetylcysteinyl)]-2-(2-chloroethylsulphinyl)ethane 7 l-[S-(Af-acetylcysteinyl)]-2-(2-chloroethylsulphonyl)ethane 8 1-[S-(N-acetylcysteinyl)]-2-(ethenylsulphonyl)ethane 9 di-GSH-SM adduct 10 l,l -sulphonylbis[(2-5 -cysteinyl)ethane] 11 l,l -sulphonylbis[2-S-(Af-acetylcysteinyl)ethane] 12 l,l -sulphonylbis(ethan-2-thiol) (putative intermediate indicated by square brackets) 13 l,l -sulphonyl-bis[2-(methylthio)ethane] 14 l-methylsulphinyl-2-[2-(methylthio)eth-ylsulphonyljethane 15 l,l -sulphonylbis[2-(methylsulphinyl)ethane].

Black, R.M., Read, R.W. (1991). Methods for the analysis of thiodiglycol sulphoxide, a metabolite of sulphur mustard, in urine using gas chromatography-mass spectrometry. J. Chro-matogr. 558 393-404. 

S -methylation (Bakke and Gustafsson, 1984). This metabolic pathway is believed to be mediated predominantly by gut flora. Of the metabolites derived from simple hydrolysis, thiodigly-col sulphoxide (TDGO) (2) was the major one, with much lower amounts of TDG (1). A separate metabolism study of TDG in the rat showed that > 90% is excreted as TDGO (Black el. al., 1993). An early metabolism study using IV administration in the rat reported excretion of the bis-glutathione conjugate of sulphur mustard (Davison et al, 1961). 

Hydrolysis of VX produces 2-diisopropy-laminoethanethiol, HSCH2CH2N(/Pr)2. A metabolite (12), derived from enzymatic S-methylation of this hydrolysis product, was identified in human plasma following an assassination with VX (Tsuchihashi et al. 1998). Experiments in rats confirmed the rapid metabolic formation of (12) from HSCH2CH2N(/Pr)2 (Tsuchihashi et al., 2000). This metabolite has not been reported in urine. By analogy with (3-lyase metabolites of sulphur mustard, it might be excreted as a sulphoxide. 

Figure 2. Molecular structures of the sulphoxide and sulphone of sulphur mustard...

Mustard will also react with a wide variety of electrophiles. Its reactions with chlorine containing reagents such as hypochlorite ion are many and varied. Depending upon conditions, mustard can be oxidised to HCl, CO2, SO2, RCl and S (e.g. by solid Ca(OCl)2) or to sulphoxide (sulphur IV) and sulphone (sulphur VI) species by hypochlorite ion in aqueous media. 

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