Analysis of the metabolic transformation of heterocyclic amines by molecular orbital calculations

Heterocyclic amines (HCAs), contained in charred parts of broiled fish and meat, show a variety of mutagenic activities. To investigate the structure-activity correlation of HCAs, molecular orbital calculations were performed for 19 HCAs. We focused our attention on the binding reaction of the nitrenium ion of HCAs to bases of DNA and calculated the activation energy for the reaction. The activation energies for guanine were found to be the smallest of those for the four bases. This explains the experimental result that HCAs react preferentially with guanine in DNA. Correlations, however were poor between the activation energy and the mutagenicity of HCAs, which indicates that the production rate and stability of nitrenium ions are more important in the mutagenicity of HCAs than the reaction rate of the ions.