With ammonia and primary amines, a thiomorpholine is formed (5-14):
Two molecules of amine may react with one of sulfur mustard (5-15):
Tertiary amines form quaternary ammonium salts (5-16):
When heated with a concentrated aqueous solution of thiourea, sulfur mustard gives the isothiouronium salt, which is decomposed by aqueous NaOH. Acidification produces the mercaptan in high yield
As is obvious from the chemistry described above, sulfur mustard can react with a number of important functional groups of the large variety of compounds present in cells and tissues. The reactive groups that are of greatest interest are the sulfhydryl group; the phosphate and pyrophosphate ions; organic phosphates such as nucleotides and phospholipids; aromatic nitrogen atoms such as in nicotinamide, adenine, cytosine, and histidine; the carboxyl groups of amino acids and of intermediates of glucose metabolism; the sulfides such as methionine and thiodiglycol; and the amino groups of amino acids, peptides, purines, and pyrimidines. It should be noted, however, that at physiologic pH, most amines are present predominantly in the protonated form rather than as the free base, diminishing the probability of extensive reaction with sulfur mustard.
Evidence that the cytotoxicity of sulfur mustard is due to the alkylation of DNA was first obtained in the late 1940s from studies with bacteria, DNA-containing bacterial viruses, and transforming DNA. The later discovery that the sensitivity of bacterial and mammalian cells is critically dependent on the cell's capacity for repairing sulfur mustard-induced DNA damage strongly supports the DNA target hypothesis.