FT-Raman, FT-IR and normal-mode analysis of carcinogenic polycyclic aromatic hydrocarbons. Part II—a theoretical study of the transition states of oxygenation of benzo(a)pyrene (BaP)

✍ Scribed by H.-P. Chiang; B. Mou; K. P. Li; P. Chiang; D. Wang; S. J. Lin; W. S. Tse

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 167 KB
• Volume: 32
• Category: Article
• ISSN: 0377-0486
• DOI: 10.1002/1097-4555(200101)32:1<53::aid-jrs667>3.0.co;2-b

✦ Synopsis

The first process in polycyclic aromatic hydrocarbons (PAH) metabolism is believed to be the oxygenation that leads to several structural isomeric epoxides. Most of these intermediates will be converted into non-toxic hydrophilic metabolites and be excreted. Because of this, metabolism has been considered to be primarily a detoxification mechanism. However, some may be activated to become ultimate carcinogens. Knowledge of the identities of these intermediates and their probabilities of formation will be of vital importance in mechanism elucidation and cancer prevention. Theoretically, epoxidation of benzo.a/pyrene (BaP) can take place at any one of the sites: 1,2-, 2,3-, 4,5-, 7,8-, 8,9-, 9,10-and 11,12-, leading to seven possible isomeric epoxides. The conformations of these isomers formed from direct oxygenation were simulated and their activation energies calculated. Among them, the 4,5-epoxide appears to be the most and the 8,9-complex the least energetically favorable. The 11,12-, 9,10-and 7,8-isomers are almost equally energetic. The rate of formation of the 7,8-isomer, which is believed to be the precursory carcinogen, relative to the 4,5-epoxide is estimated to be 9.1 × 10 -4 : 1. On the other hand, the relative rates of 1,2-and 2,3-complexes are extremely low. When the protoporphyrin group is used for simulation, the BaP plane is seen parallel to the porphyrin plane in the 1,2-and 2,3-complexes, but angled away to various degrees in all other epoxides. The parallel orientation results in a significant lowering of the activation energy, making 1,2-and 2,3complexes the most favorable intermediates. This is in agreement with chromatographic analyses of BaP metabolism in liver microsomes. In these experiments, 3-hydroxy-BaP is the major product.