Benzo fjord region

Fig. 10.12. Upper part The K, M, bay, and fjord regions of three isomeric tetracyclic aromatic hydrocarbons (benz[a]anthracene (BaA, 10.31), chrysene (CR, 10.32), and benzo[c]phenanthrene (BcPh, 10.33)). Lower part. The three pairs of enantiomeric (S,R)- and (R,S)-K-region epoxides and...

The formation and reactivity of dihydrodiol epoxides is now illustrated for benzo[a]pyrene (BaP, 10.34, Fig. 10.13), one of the most extensively investigated PAHs and a highly active carcinogen. However, far from being exclusive to BaP, this toxification pathway is known to occur for a number of PAHs containing a bay or fjord region. 

Substitution at bay/fjord region benzo ring J, if ring substitution at each and every bay/fjord region benzo ring Prevent formation of bay/ fjord region diol epoxide... 

Amin, S., Desai, D., Dai, W., Harvey, R.G., and Hecht, S.S. (1995) Tumori-genicity in newborn mice of fjord region and other sterically hindered diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[de/p] chrysene), 4H -cyclopenta[de/]chrysene and fluoranthene. Carcinogenesis, 16, 2813-2817. 

Amin, S., Krzeminski, J., Rivenson, A., Kurtzke, C., Hecht, S.S., and El-Bay-oumy, K. (1995) Mammary cardno-genidty in female CD rats of fjord region diol epoxides of benzo[c] phenanthrene, benzo[g]chrysene and dibenzo[a,l]pyrene. Carcinogenesis, 16, 1971-1974. 

In addition to syn- and a t/-bcPhDE s four more fjord region diol epoxides have been synthesised and investigated, viz., syn and anti-benzo[c]chrysene DE s (BcChDE) as well as syn- and anti-benzo[g]chrysene DE s (BgChDE) [87]. All six fjord-region diol... 

A number of instances can be cited from the literature wherein the isosteres had similar transformations. Bacterial dioxygenase-catalyzed ci5-dihydroxylation of the tetracyclic arene benzo[c]phenanthrene was found to occur exclusively at fjord region (cavity region) bonds. The isosteric compounds benzo[b]naphthol [l,2-d]furan and benzo[b]naphthol[l,2-d]thiophene were also similarly ci5-dihydroxylated at the fjord region bonds by bacterial dioxygenases (Boyd et al., 2001) (see Fig. 4.3). The isosteres 1,2-dihydronaphthalene, 2,3-dihydrobenzothiophene, and 2,3-dihydro-benzofuran gave similar corresponding diol products on incubation with Pseudomonas putida UV4. Microbes that possess the metabolic pathways to metabolize benzene, when substituted by... 

This structure-activity relationship has been supported by several findings. According to Iball index which is proportional to the fraction of subject animal that shows a carcinogenic response divided by the mean latent period, dibezo(a,l)pyrene has the maximum value of 74, benzo(a)pyrene has 72, other compounds with a bay region in their structures have values above 50 while compounds such as fluoranthene, tiiphenylene, and phenanthrene without any bay or fjord region have a value of 0 [11]. 

The diol epoxides (83) and (8 ) of the carcinogen fluoroanthene have been prepared. MO theory has been used to predict that (83) should be substantially more reactive than (84) and this has been verified by mutagenicity tests. Force field molecular structures for the fjord region diol epoxides of benzo s Pheriari thi ene (85) have revealed sterlc crowding lidiich influences the relative confoimer stabilities in this system. ... 

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