Reactivity of methylazoxymethanol and its metabolites with nucleophilic centers of DNA bases: a semi-empirical NDDO molecular orbital study.
The NDDO semiempirical molecular orbital method (Kikuchi, 1977; Kikuchi and Maeda, 1977) was used to characterize the reactivities of methylazoxy-methanol (MAM) and its metabolites with DNA nucleophilic base sites. The physical association of MAM was found to occur at the guanine N7 and 06 atoms, while the ultimate alkylation reaction by MAM was predicted to occur at the guanine N7 atom more easily than at the 06 atom of guanine. These trends were also observed in the results for MAM metabolites, methylazoxy formaldehyde (MAF) and methyloazoxy carboxylic acid (MAA), and can explain the experimentally observed selectivity of MAM alkylation on DNA bases (Matsumoto and Higa, 1966; Schank and Magee, 1967). Although the methyldiazonium ion has the highest reactivity with the guanine N7 atom among the MAM metabolites, it is proposed that MAF is another candidate to react directly with the N7 atom of guanine.
D001391:Azo Compounds; D003596:Cytosine; D004247:DNA; D006147:Guanine; D006860:Hydrogen Bonding; D008745:Methylation; D008746:Methylazoxymethanol Acetate; D008968:Molecular Conformation; D013816:Thermodynamics
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; D006147:Guanine; D003596:Cytosine; D004247:DNA