CONFORMATIONAL STUDIES OF STEREOISOMERIC TETROLS DERIVED FROM SYN-DIBENZO[A,L] AND ANTI-DIBENZO[A,L] PYRENE DIOL EPOXIDES

An understanding of the conformational behavior of the stereoisomeric tetrols at the 11,12,13,14-positions of dibenzo[a,l]pyrene (DB[a,l]P) is essential for the spectroscopic identification of DNA adducts deriv ed from the biologically highly active fjord region syn- and anti-DB[a ,l]P-11,12-diol 13,14-epoxides. Conformational effects are expected to play an important role in DNA-DB[a,l]P diol epoxide reactivity, base- sequence specificity, and conformation dependent repair. The results o f conformational studies on trans-anti-, cis-anti-, and cis-syn-DB[a,l ]P tetrol isomers are presented and compared to the results obtained p reviously for trans-syn-DB[a,l]P tetrol (Carcinogenesis 17, 829-837, 1 996). Molecular mechanics, dynamical simulations, and semiempirical ca lculations of electronic transitions are used to interpret the low-tem perature fluorescence spectra and H-1 NMR data. Molecular dynamics sim ulations (in vacuo) identified two conformers (I and II) for each of t he tetrol isomers; in all conformations the aromatic ring system is se verely distorted. Fluorescence line-narrowing (FLN) spectroscopy ident ified tyro distinct conformational species for the trans-anti isomer, one occurring in ethanol and the other occurring in a glycerol/water m atrix. The corresponding structures are assigned based on the S-1 <-- S-0 transition energies calculated for conformers I and II, respective ly. H-1 NMR spectroscopy confirmed the structure of conformer I at roo m temperature. In contrast to trans-syn-DB[a,l]P tetrol (where the maj or conformation was identified as a boat structure), both conformation s of trans-anti-DB[a,l]P tetrol feature a half-chair structure for the cyclohexenyl ring with different orientations of the hydroxyl groups. For cis-anti- and cis-syn-DB[a,l]P tetrols, only a single conformer i s detected by FLN spectroscopy. The NMR results for the latter appear to be most consistent with a mixture of two half-chair conformers I an d II, while for the cis-anti isomer a flattened, boatlike conformation was observed. The generally good agreement between the NMR coupling c onstants and those estimated theoretically indicates that these struct ures should serve as good starting points for spectroscopic or computa tional studies of DNA adducts derived from DB[a,l]P diol epoxides.