Molecular Modeling of Toxic Indole Derivatives from High Temperature Cooking

Abstract

More than two decades ago, Japanese scientists discovered a new family of highly mutagenic compounds classified as heterocyclic aromatic amines from roasted meat and grilled Fish. This group of compounds will form the basis of this investigation from a theoretical perspective. In order to simulate high temperature cooking and explore the thermochemical properties of these compounds, high level quantum calculations were employed. Accordingly, the theoretical behaviour of indole derivatives; isoindazole, 1-methyl indole, 4,7-dimethyl isoindazole and carbazole were explored at a pressure of 1 atmosphere over a wide range of pyrolysis temperatures (323-923 K) typically at temperature increments of 50 K. Ab initio analytical gradients at MP2 level of theory with 3-21G and 6-31G(d,p) basis sets and Molecular Mechanics (MM) with universal force field (UFF) from Gaussian 03 computational platform were used for geometry optimization, internal energy calculations, molecular orbitals, and vibrational frequencies. It was observed that the internal energy for isoindazole at 323 K was 75.80 kcal/mol whereas that of carbazole was 123.78 kcal/mol under similar conditions of pressure and temperature. The stability of these molecular compounds decreased with increase in pyrolysis temperature. To make decent conclusions on the potency of these indole derivatives and their effect on human health, toxicity values were estimated using Quantitative Structural Activity Relationship (QSAR) method found in HypeChem computational software.  Toxicity indices for isoindazole, 1-methyl indole, 4,7-dimethyl isoindazole and carbazole were -0.16, 0.01, 0.14 and -0.07 respectively, while those for their corresponding radicals were -0.12, -0.21, 0.19 and -0.17. These values point to highly hydrophilic species which indicate that they are very toxic. The thermochemical, and electronic properties of these compounds and their analog radicals will be presented.  Additionally, theoretical NMR chemical shifts for the most toxic by-product of high temperature cooking are also reported in this work.