INFIQC   05475
INSTITUTO DE INVESTIGACIONES EN FISICO- QUIMICA DE CORDOBA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Quantum-mechanical calculations of the interactions of mutagenic heteroaromatic amines with DNA
Autor/es:
BOROSKY, GABRIELA L.
Lugar:
Montevideo
Reunión:
Congreso; XLII Congreso de Químicos Teóricos de Expresión Latina, Quitel 2016; 2016
Resumen:
Heteroaromatic amines found in well-done/over cooked meats and protein rich foods have been confirmed to be mutagenic and carcinogenic. They are metabolically transformed into aryl N-hydroxylamines, and further activated to sulfuric or acetic acid esters. The esters undergo N-O bond cleavage to yield highly reactive arylnitrenium ions. These nitrenium ions are the ultimate electrophilic metabolites that covalently bind and modify DNA, leading to mutations and cancer. Nitrenium ion stability has been pointed out to be important in determining the bioactivity of aromatic and heteroaromatic amines.Computational methods were applied to elucidate the factors determining the variations in mutagenic activity within groups of isomeric heteroaromatic amines differing in the position of methyl groups. The nitrenium ions derived from these molecules present very similar relative stabilities. In this way, the aim of this work was to determine the influence of methyl substitution on structure-mutagenicity relationships. The role of the molecular structure on the bioactivity of this type of compounds was analyzed in the search for correlations between computed properties and the mutagenic potencies reported in the literature. The effect of the amine structure on the formation of noncovalent complexes and covalent adducts with a DNA segment was evaluated by quantum-mechanical calculations performed for a two-layer ONIOM(ωB97X-D/6-31G*:PM6) system. Molecular docking techniques were also carried out. The influence of the environment was considered by means of the IEFPCM continuum model.