Reactivity of chloroethyl sulfides in the presence of a chlorinated prophylactic: a kinetic study by EPR/spin trapping and NMR techniques

This study reports the kinetic reaction of a chlorinated glycoluril, 1,3,4,6-tetrachloro-7, 8-diphenyl-2,5-diimino glycoluril, also known as S-330, with butyl 2-chloroethyl sulfide (half-sulfur mustard, H-MG) and bis-(2-chloroethyl) sulfide (sulfur mustard, HD) using electron paramagnetic resonance (EPR)/spin trapping and nuclear magnetic resonance (NMR) techniques. Both H-MG and HD are highly reactive in water and are capable of alkylating a variety of critical target molecules. It is well known that compounds containing reactive chlorine are useful neutralizers of HD and other vesicating agents. Organic compounds containing a chloroamide group are generally preferred. Currently, the reactive mechanism of this chlorinated glycoluril with these chloroethyl sulfides has not been documented. The kinetic experiments were performed by adding the monofunctional sulfur mustard (H-MG) directly to the spin trap agent alpha-phenyl-N-tert-butylnitrone (PBN, pH 7.1). The intensity of the EPR spectra obtained from the resulting spin adduct (hyperfine coupling constants aN = 1.45 mT and abetaH = 0.225 mT) was sensitive to the rate at which the spin adduct was formed. Different concentrations of the chloroamide were added to the reaction mixtures of PBN and H-MG. The EPR spectra of separate identical reaction mixtures were recorded with the spectrometer set for kinetic experiments. The rate constant determined by EPR was 1.78 +/- 0.14 x 10(7) M(-1)s(-1). It was found that S-330 reacts 55 times faster than PBN. The results obtained for S-330 by EPR indicate that S-330 is an efficient scavenger of H-MG. Furthermore, a 13C-NMR chemical shift of 0.903 +/- 0.002 ppm was observed for the Cl-N-C-N-Cl carbon in S-330 after exposure to HD (1 mM). In addition, the decay of 13C-NMR resonance at 91.7 ppm chemical shift was observed in the presence of HD. The 13C-NMR data showed that the formation of the ethylene sulfonium ion usually found in the case of HD was not observed in the presence of S-330.