Abstract
The molecular structures of two racemic trans-tetrahydrotetrols formed by hydrolysis of the (±)anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro derivatives of the strong carcinogen benzo[a]pyrene and the weak carcinogen chrysene have been determined by X-ray crystallographic methods.3 Focusing on the (+)isomers, the stereochemical features of the two tetrols are discussed in detail to determine structural differences, which can be related to the different biological activity of their parent hydrocarbons, since they provide a model for the hydrocarbon moiety in the major PAH-DNA adduct. As a result of this study, a tentative correlation can be stated between biological activity of quasi-planar bay-region PAHs and the presence of structural features, which can decrease the steric hindrance of the aromatic skeleton and the other hydroxy groups on the pseudo-axial O4, which mimics the position of the covalent bond to DNA. The significant structural features seem to be an out-of-plane distortion with a negative torsion angle at the bay region and a half chair conformation of the saturated ring distorted toward the envelope with C8 at the tip as in BPT, in addition to the axial and pseudo-axial conformations of the hydroxy groups at C9 and C10 due to the near bay region. They may be considered generated by trans-opening of the oxirane ring in an anti-diol epoxide biologically active because it is highly strained. The strains, derived from the activation of bay-region PAHs with a negative torsion angle, seem greater in an anti-diol epoxide relative to the syn-isomer. Thus, when the strains are released, the derived trans-tetrol occurs with structural features, which seem to better fit the target. As a consequence, the presence of a methyl group at a bay region should increase the biological activity of a PAH, imposing greater strains to the structure of the anti-diol epoxide.
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Bachechi, F., Polcaro, C. Crystal Structures of trans-Tetrahydrotetrols of Benzo[a]pyrene and Chrysene: A Possible Structure-Activity Relationship in Quasi-Planar Bay-Region Polycyclic Aromatic Hydrocarbons. Structural Chemistry 10, 135–148 (1999). https://doi.org/10.1023/A:1022037431181
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DOI: https://doi.org/10.1023/A:1022037431181