title: Carcinogenicity of acrylamide: a computational study.
abstract: This paper reports a series of ab initio, density functional theory (DFT), and semiempirical molecular orbital (MO) calculations concerning the reaction between the ultimate carcinogen of acrylamide and guanine. Acrylamide--a product of the Maillard reaction--is present in a variety of fried and oven-cooked food. After intake, it is epoxidized by cytochrome P450 2E1 to yield the ultimate carcinogen--glycidamide. Effects of solvation were considered using the Langevin dipoles (LD) model of Florian and Warshel and the solvent reaction field (SCRF) model of Tomasi and co-workers. In silico activation free energies are in very good agreement with the experimental value of 22.8 kcal/mol. This agreement presents strong evidence in favor of the validity of the proposed S N2 reaction mechanism and points to the applicability of quantum chemical methods to studies of reactions associated with carcinogenesis. In addition, insignificant stereoselectivity of the studied reaction was predicted. Finally, the competing reaction of glycidamide with adenine was simulated, and the experimentally observed regioselectivity was successfully reproduced.
authors: National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
authors: Katja
authors: K
authors: Galesa
authors: Urban
authors: U
authors: Bren
authors: Agata
authors: A
authors: Kranjc
authors: Janez
authors: J
authors: Mavri
mesh_terms: D020106:Acrylamide / Q000737:chemistry / Q000633:toxicity*; D000225:Adenine / Q000737:chemistry; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D004852:Epoxy Compounds / Q000737:chemistry; D005504:Food Analysis; D006358:Hot Temperature; D015416:Maillard Reaction; D008433:Mathematics; D013816:Thermodynamics
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; D000225:Adenine