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, 677-686]. 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-N(6)dA 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-N(6)dA adducts exist in conformations I and II, with their fluorescence origin bands at approximately 382 and approximately 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-N(6)dA, with its origin band at approximately 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 (1)H 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 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-N(6)dA. 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-N(6)dA 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.
Jankowiak
R
R
Ames Laboratory-U.S. Department of Energy and Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA. jankowiak@ameslab.gov
Lin
C H
CH
Zamzow
D
D
Roberts
K P
KP
Li
K M
KM
Small
G J
GJ
D001580:Benzopyrenes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D001580:Benzopyrenes; D018736:DNA Adducts; D003839:Deoxyadenosines; D004852:Epoxy Compounds; C087596:11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo(a,l)pyrene; D004247:DNA