Computational Insights into the Chemical Structures and Mechanisms of the Chromogenic and Neurotoxic Effects of Aromatic γ-diketones
journal contributionposted on 05.03.2003, 00:00 authored by Chang-Guo Zhan, Peter Spencer, David A. Dixon
The chromogenic properties of various candidate structures, i.e., isoindole monomers and dimers and their derivatives, of the chromophores formed from the reactions of 1,2-diacetylbenzene (1,2-DAB), a typical representative of chromogenic and neurotoxic aromatic γ-diketones, with NH3, amino acids, and proteins, have been calculated by using density functional theory. The calculated results indicate that the isoindole monomers should not exhibit a color, whereas the isoindole derivative dimers should all be colored. Further oxidization of the isoindole derivative dimers can significantly change the colors of the dimers, and the results calculated for the oxidized isoindole derivative dimers are completely consistent with all of the experimental data for the chromogenic and neurotoxic effects of 1,2-DAB. It has been demonstrated that the violet/blue chromophores formed from the reactions of 1,2-DAB with amino acids/proteins under neutral and acidic conditions are likely to be the oxidized isoindole derivative dimer structures (like 7b) cross-linking the proteins, whereas the brown chromophores formed when pH ≥ 7.5 could be the oxidized dimer structures (like 7a) without cross-linking proteins. Our results strongly support the conclusion that the chromogenic effects of aromatic γ-diketones are closely related to their neurotoxic effects and further predict that both the chromogenic and neurotoxic effects are associated with the same chemical reaction process under the neutral and acidic conditions. Such a reaction process most likely starts from the formation of the isoindole−protein adducts followed by the dimerization and further oxidization.