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 dio l epoxide (DB [a,l]PDE)-derived deoxyadenosine (dA) adducts are presented a nd compared with those previously obtained for the stereoisomeric DB[a,l]P tetrols [Jankowiak, R., et al. (1997) Chem. Res. Toxicol. 10, 677-686]. In contrast to DB[a,l]P tetrols, for which only tl ans isomers exhibited two c onformers, all stereoisomeric dA adducts adopt two different conformations with either half-chair or half-boat structures for the cyclohexenyl ring, a nd an "open"- or "folded"-type configuration between dA and the DB[a,l]P mo iety. The major conformations observed for trans-syn-, cis-syn-, and cis-an ti-DB [a,l]PDE-14-N(6)dA could be assigned on the basis of the previous cal culations for the DB[a,l]P tetrols. The major conformers of the trans-syn- and cis-syn-DB[a,l]PDE-14-N(6)dA adducts exist in conformations I and II, w ith their fluorescence origin bands at similar to 382 and similar to 389 nm , respectively. In conformation I, the cyclohexenyl ring adopts a half-boat structure with dA in a pseudoaxial position (an open configuration), where as the cyclohexenyl ring in conformation II adopts a half-chair structure w ith dA in pseudoequatorial position (a folded configuration). The major con formation of cis-anti-DB [a,l] PDE-14-N(6)dA, with its origin band at simil ar to 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 fluor escence spectra and H-1 NMR coupling constants observed for the trans-anti- DB [a,l] PDE-14-N(6)dA adduct. The major conformer of this adduct has a hal f-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 -N(6)dA. This new structure is labeled as conformer II'. Its (0,0) fl uorescence band is at 388.1 and 388.3 nm in ethanol and glyceror/water glas ses, respectively, consistent with the folded-type configuration revealed b y the calculations. The fluorescence line-narrowed spectra reveal that the trans-syn-, cis-syn-, trans-anti-, and cis-anti-DB [a,l] PDE-14-N(6)dA addu cts can be distinguished. Thus, their spectra should prove useful for ident ification of DB [a,l] P-DNA adducts formed at low levels in biological samp les.