Methylhydrazines

Abstract: Hydrazines are an important class of compounds which find considerable technical and commercial applications. Furthermore, numerous biological activities of hydrazine derivatives have been discovered which make them potent drugs, peptidomimetics, and pesticides. 2] Besides their synthetic relevance, hydrazines are also interesting from a mechanistic point of view, as they have two adjacent nucleophilic nitrogen centers. Unsymmetrically substituted hydrazines are, therefore, ambident nucleophiles, and the factors that determine the regioselectivities of their reactions have been studied intensively. Typically, protonations as well as alkylations of alkyl-substituted hydrazines take place at the more-substituted nitrogen atom. Thus, in the case of 1,1-dialkyl hydrazines, quaternary ammonium salts are formed. 3] Kinetic investigations focused on the parent hydrazine and little is known about the nucleophilic reactivities of substituted hydrazines though this information is crucial for predicting the regioselectivities in a variety of heterocyclic syntheses. To investigate the factors which control relative reactivities of the different sites of unsymmetrical hydrazines we

Abstract: The methylhydrazines, monomethylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine, are known carcinogens but only weak mutagens in the Ames test. Chemical oxidation of these compounds by potassium ferricyanide greatly enhanced their mutagenicity to an Escherichia coli ada mutant and converted them into inducers of the adaptive response of E. coli to alkylation damage. Enzymatic oxidation of monomethylhydrazine by horseradish peroxidase-H2O2 also yielded products which induced the adaptive response. Thus, methylhydrazines can be oxidized to active DNA-methylating derivatives which generate methylphosphotriesters (the inducing signal of the adaptive response), O6-methylguanine and/or O4-methylthymine (the miscoding bases repaired by the Ada protein) in DNA. These observations support the suggestion that metabolic oxidation of methylhydrazines in mammalian systems may be required to generate the mutagenic/carcinogenic derivatives.