Veterans at Risk The Health Effects of Mustard Gas and Lewisite (1993) / Chapter Skim
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5 Chemistry of Sulfur Mustard and Lewisite
5 Chemistry of Sulfur Mustard and Lewisite
Pages 71-80
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From page 71... ...
The synthesis and chemistry of sulfur mustard, or mustard gas, have been studied and reviewed extensively. Chemical and physical data regarding sulfur mustard were presented in Table 3-1.
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From page 72... ...
The rate constant for the hydrolysis of sulfur mustard, as determined by acid production, is markedly dependent on temperature and the presence of chloride ion, which retards the hydrolysis rate without altering the reaction products. The retardation of hydrolysis by added chloride is consistent with the reversibility of the activation step to cyclic sulfonium ion.
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From page 73... ...
The relative affinities of nucleophiles are quantitatively described by their competition factors, which compare the rate of constants for bimolecular reactions of cyclic ethylene sulfonium ion with a given nucleophile (Ka) and water (Ko)
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From page 74... ...
This is consistent with the proposed reaction mechanism, in which the rate-limiting step in the reaction of sulfur mustard in aqueous media is the formation of the cyclic sulfonium intermediate. In addition to the potential contribution of sulfonium salts to the biologic activity of sulfur mustard, the oxidized forms of sulfur mustard may also be of importance.
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From page 75... ...
The later discovery that the sensitivity of bacterial and mammalian cells is critically dependent on the cell's capacity for repairing sulfur mustardinduced DNA damage strongly supports the DNA target hypothesis.
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From page 76... ...
The molecular basis for this greater toxicity is the ability of sulfur mustard to form interstrand cross-links between guanines of the double helix, which prevents strand separation during replication. In addition, 7-aLkylguanines and 3-alkyladenines of DNA are unstable and are released spontaneously from sulfur mustardtreated DNA at physiologic pH and temperature by cleavage of the N-9 glycosyl bond to give an apurinic site.
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From page 77... ...
In particular, enzymes that maintain calcium homeostasis are sulfhydryl dependent, and sulfhydryl depletion may lead to elevated cellular calcium levels and cell death. Glutathione is also thought to be critical in reducing reactive oxygen species in the cell and preventing lipid peroxidation and loss of membrane integrity.
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From page 78... ...
However, the increased incidence of solid tumors seen with nitrogen mustard would support the conclusion that exposure of the lungs and skin to sulfur mustard produces a carcinogenic effect on these tissues. Similarly, the delayed pulmonary toxicity seen in a small percentage of patients treated with nitrogen mustards would suggest that long-term damage to the lungs would be expected with intense exposure of the lungs to sulfur mustard.
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From page 79... ...
Hydrogen peroxide causes decomposition of the ethers and thioethers in neutral or acid solution, giving free arsenic acids. Little information is available in the literature concerning the reactions of Lewisite with biologically important molecules, although it is reasonable to assume that, as with sulfur mustard, DNA is a major target.
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From page 80... ...
1962. Biological ALkylating Agents: Fundamental Chemistry and Design of Compounds for Selective Toxicity.
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