Benzo pyrenes structure

Feng, B., Gorin, A., Hingerty, B.E., Geacintov, N.E., Broyde, S., and Patel, D.J. (1997) Structural alignment of the (+)-trans-attti-benzo[ ]pyrene-dG adduct positioned opposite dC at a DNA template-primer junction. Biochemistry, 36,13769-13779. 

Being interested here in the volatile components of coffee aroma, we shall arbitrarily limit the list of the aromatic hydrocarbons to tricyclic structures. The higher fused polycyclic hydrocarbons (fluoranthene [206-44-0], pyrene [129-00-0], chrysene [218-01-9], benz[ ]anthracene (1,2-benzanthracene) [56-55-3], benz[< ]acephenanthrylene (3,4-benzofluoranthene) [205-99-2], benzo[ ]pyrene (3,4-benzopyrene, 3,4-BP) [50-32-8], benzo[e]pyrene (1,2-benzopyrene) [192-97-2], perylene [198-55-0], benzo[g,/i,/]perylene (1,12-benzopyrene) [191-24-2], and dibenz[ ,//]anthracene (1,2,5,6-dibenzanthracene) [53-70-3]) cannot be considered as a part of the aroma. However, as some of these, specially benzo[o pyrene, are known for carcinogenic properties, they have been particularly analyzed in food subject to roasting or smoke-curing. 

Fig. 1. Structures of benzo[<2]pyrene, 3-methylcholanthrene and dioxin. Benzo[<2]-pyrene and 3-methylcholanthrene are PAH compounds, but dioxin is not. Benzo [ ] pyrene is converted to the ultimate carcinogen BPDE by CyplAl.

Benzo[a]pyrene, a molecule with five, fused, hexagonal rings, is among the most carcinogenic of the polycyclic aromatic hydrocarbons (PAHs). Such biological activity may be related to the electronic structure of benzo[a]pyrene and its metabolites. Ionization energies of these molecules therefore have been investigated with photoelectron spectroscopy [28]. 

FIGURE 2.6 The procarcinogen benzo[a]pyrene oriented in the CYPlAl active site (stereo view) via n- n stacking between aromatic rings on the substrate and those of the complementary amino acid side chains, such that 7,8-epoxidation can occur. The substrate is shown with pale lines in the upper structures. The position of metabolism is indicated by an arrow in the lower structure (after Lewis 1996). 

Some examples of different types of hydrocarbons are given in Figure 9.1. Nonaromatic compounds without ring structure are termed aliphatic, whereas those with a ring structure (e.g., cyclohexane) are termed alicyclic. Aromatic hydrocarbons often consist of several fused rings, as in the case of benzo[a]pyrene. 

The structures of some PAHs of environmental interest are given in Figure 9.1. Naphthalene is a widely distributed compound consisting of only two fused benzene rings. It is produced commercially for incorporation into mothballs. Many of the compounds with marked genotoxicity contain 3-7 fused aromatic rings. Benzo[a] pyrene is the most closely studied of them, and will be used as an example in the following account. 

Figure 2. 7-Methylbenz[a]anthracene and benzo[a]pyrene indicating those regions defined as bay regions and the structures of the corresponding bay region dihydrodiol epoxides.

The reaction of metabolically generated polycyclic aromatic diol epoxides with DNA Ua vivo is believed to be an important and critical event in chemical carcinogenesis Cl,2). In recent years, much attention has been devoted to studies of diol epoxide-nucleic acid interactions in aqueous model systems. The most widely studied reactive intermediate is benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), which is the ultimate biologically active metabolite of the well known and ubiquitous environmental pollutant benzo(a)pyrene. There are four different stereoisomers of BaPDE (Figure 1) which are characterized by differences in biological activities, and reactivities with DNA (2-4). In this review, emphasis is placed on studies of reaction mechanisms of BPDE and related compounds with DNA, and the structures of the adducts formed. 

Figure 3. Structure of major DNA adduct detected in many in vivo systems as a result of metabolic activation of benzo[a]pyrene or the reaction of anti-B[alPDE with DNA jji vitro dR=deoxyribose moiety.

Recent structure-activity studies of 1-alkylbenzo[a]pyrenes also suggest that DNA intercalation of benzo[a]pyrene (BP) metabolites plays a role in the mechanism of BP carcinogenesis (38). The addition of bulky alkyl groups at the 1-position of BP, which inhibit DNA intercalation of 1-alkyl-BP metabolites (19), causes a reduction in carcinogenic activity. 

This procarcinogen undergoes metabolic conversion to benzo[a]pyrene diol epoxides, BPDEs (5,28-31), which have been the focus of structural and conformational studies by theoretical and experimental methods. These chemically reactive BPDEs are involved in covalent binding to DNA (13-22). 

A theoretical analysis is presented for the binding of the four dia-stereoisomers of benzo[a]pyrene diol epoxides (BPDEs) to N2(g), N6(a), 06(G) and NU(c). Molecular models for binding and stereoselectivity involving intercalation, intercalative covalently and externally bound forms are presented. Molecular mechanics calculations provide the energetics which suggest possible structures for the formation of each of the principal DNA-BPDE complexes. Stereographic projections are used to illustrate the molecular structures and steric fits. The results of previous calculations on intercalation and adduct formation of BPDE l(+) in kinked DNA (37) are summarized and extended to include the four diastereoisomers l( ) and II( ). The theoretical model is consistent with the observed experimental data. 

The results of a crystal structure formed by a trans opening of the BPDE l(+) to yield 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPTOH) shows a Cde (90) conformation of the ring. The 07-HOT and O8-H8 groups are de, and the 09-H9 and 010-H10 are also de. The torsion angles of the benzo ring are in best agreement with our second most stable structure, Cde, of the anti BDE-N2(G) trans adduct as is seen from Table III. In adduct formation to N2(G) the trans adduct is the major product (13-22) ... 

Lemaire-Gony, S. and P. Lemaire. 1992. Interactive effects of cadmium and benzo[a]pyrene on cellular structure and biotransformation enzymes of the liver of the European eel Anguilla anguilla. Aquat. Toxicol. 22 145-160. 

FIGURE 7. Nitroarene structures analogous to that of benzo(a)pyrene... 

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