Chemistry of Mustard Compounds

The two main categories of mustard compounds are sulfur mustards and nitrogen mustards. Sulfur mustard was the first vesicant chemical weapon used. Its first widespread use was recorded in the World War One. After a number of sporadic military attacks, another widespread use of sulfur mustard occurred in the Iran-Iraq war. Nitrogen mustard derivatives are used in chemotherapy. HN-1, HN-2, HN-3 are the most important forms of nitrogen mustards. Nitrogen mustard HN-2 is chlormethine (Mechlorethamine) and has been used for treatment of multiple cancer diseases such as Hodgkin’s disease. Sulfur mustard has the chemical name bis(2-chloroethyl) sulfide and the IUPAC name 1-chloro-2-(2-chloroethylsulfanyl) ethane. It is also known as mustard, mustard gas, HD or Yperite. The compound is highly reactive and has carcinogenic, cytotoxic and powerful vesicant characteristics. Mustard gas was first synthesized from the reaction of ethylene and sulfur dichloride (Levinstein process) through an electrophilic addition mechanism. Later, it was prepared by the reaction of thiodiglycol with phosphorus trichloride (Meyer reaction) in a substitution reaction. Finally, reaction of concentrated hydrochloric acid (HCl) and thiodiglycol resulted in the production of sulfur mustard. Pure mustard is a viscous, colorless and odorless liquid which evaporates slowly in the atmosphere. Cytotoxicity of sulfur mustard stems from the formation of electrophilic species called sulfonium cation upon nucleophilic attack. This transient cation then readily reacts with macromolecules of DNA, RNA and proteins or with water to form the corresponding hydroxyl compounds. DNA Cross-linking of guanine by sulfur mustard and its interaction with imidazole are well studied. Nitrogen mustard (NM) and sulfur mustard (SM) slightly differ in properties. Like sulfur mustard, nitrogen mustard compounds are also alkylating agents and are reactive compounds that covalently bind to nucleophilic groups such as amine, carboxyl, sulfhydryl and imidazole moieties in DNA, RNA and proteins. Decontamination of SM can be achieved via hydrolysis in presence of aqueous solutions of sodium hypochlorite and or chloramine-T; in which HD decomposes into thiodiglycol non-poisonous product. No specific antidote for SM poisoning has been introduced. However, some formulations have been introduced as effective skin decontaminants.