Spectral and conformational analysis of deoxyadenosine adducts derived from syn- and anti-dibenzo[a,l]pyrene diol epoxides: Fluorescence studies

Low-temperature fluorescence spectra and results of conformational studies with trans-syn-, cis-syn-, trans-anti-, and cis-anti- dibenzo[a,l]pyrene diol epoxide (DB[a,l]PDE)-derived deoxyadenosine (dA) adducts are presented and compared with those previously obtained for the stereoisomeric DB[a,l]P tetrols [Jankowiak, R., et al. (1997) Chem. Res. Toxicol. 10, 677686]. In contrast to DB[a,l]P tetrols, for which only trans isomers exhibited two conformers, all stereoisomeric dA adducts adopt two different conformations with either half-chair or half boat structures for the cyclohexenyl ring, and an 'open'- or 'folded'-type configuration between dA and the DB[a,l]P moiety. The major conformations observed for trans-syn-, cis-syn-, and cis-anti-DB[a,l]PDE-14-N⁶dA could be assigned on the basis of the previous calculations for the DB[a,l]P tetrols. The major conformers of the trans-syn- and cis-syn-DB[a,l]PDE-14-N⁶dA adducts exist in conformations I and II, with their fluorescence origin bands at ~382 and ~389 nm, respectively. In conformation I, the cyclohexenyl ring adopts a half-boat structure with dA in a pseudoaxial position (an open configuration), whereas the cyclohexenyl ring in conformation II adopts a half-chair structure with dA in pseudoequatorial position (a folded configuration). The major conformation of cis-anti-DB[a,l]PDE-14-N⁶dA, with its origin band at ~389 nm, was also assigned as a folded-type configuration with a half-chair structure in the cyclohexenyl ring. Molecular mechanics and dynamical simulations were performed for interpretation of the low-temperature fluorescence spectra and ¹H NMR coupling constants observed for the trans- anti-DB [a,l] PDE-14-N⁶dA adduct. The major conformer of this adduct has a half-chair structure in the cyclohexenyl ring, but a deviation from planarity in the fjord region different from that of conformer II of cis-anti-DB [a,l]PDE-N⁶dA. This new structure is labeled as conformer II'. Its (0,0) fluorescence band is at 388.1 and 388.3 nm in ethanol and glycerol/water glasses, respectively, consistent with the folded-type configuration revealed by the calculations. The fluorescence line-narrowed spectra reveal that the trans-syn-, cis-syn-, trans-anti-, and cis-anti-DB[a,l]PDE-14-N⁶dA adducts can be distinguished. Thus, their spectra should prove useful for identification of DB[a,l]P-DNA adducts formed at low levels in biological samples.