Structure elucidation of the adducts formed by fjord-region Dibenzo[a,l]pyrene 11,12-dihydrodiol 13,14-epoxides and deoxyadenosine.
Model adducts to be used in the identification of biologically formed adducts were synthesized by reaction of fjord-region dibenzo[a,l]pyrene 11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE) and deoxyadenosine (dA). The (+/-)-anti-DB[a,l]PDE was reacted with dA in dimethylformamide at 100 degrees C for 30 min to give four DB[a, l]PDE-14-N(6)dA adducts: (-)-anti-trans (26%), (+)-anti-trans (26%), (-)-anti-cis (17%), and (+)-anti-cis (17%). The (+/-)-syn-DB[a,l]PDE was reacted with dA under the same conditions to yield four DB[a, l]PDE-14-N(6)dA adducts and one N7Ade adduct: (+)-syn-cis (19%), (+)-syn-trans (13%), (-)-syn-cis (19%), (-)-syn-trans (13%), and (+/-)-syn-DB[a,l]PDE-14-N7Ade (22%). The structures of the eight stereoisomers of DB[a,l]PDE-14-N(6)dA were unequivocally assigned by reacting optically pure (-)-anti-DB[a,l]PDE and (+)-syn-DB[a,l]PDE with dA and by a combination of NMR, circular dichroism, and fast atom bombardment mass spectrometry. Reactions at 100 degrees C yielded mainly the trans-opened adducts at the benzylic C-14 position for both (+/-)-anti-DB[a,l]PDE and (-)-anti-DB[a,l]PDE, whereas (+/-)-syn-DB[a,l]PDE and (+)-syn-DB[a,l]PDE afforded mainly cis-opened adducts. At room temperature, however, only trans-opened adducts were obtained from (+/-)-anti-DB[a,l]PDE and only cis-opened adducts from (+/-)-syn-DB[a,l]PDE. Steric hindrance created by the fjord region may be an important factor for the stereoselectivity observed at room temperature.
Li
K M
KM
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
George
M
M
Gross
M L
ML
Seidel
A
A
Luch
A
A
Rogan
E G
EG
Cavalieri
E L
EL
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000138:chemical synthesis*; D003839:Deoxyadenosines / Q000737:chemistry*; D004101:Dihydroxydihydrobenzopyrenes / Q000737:chemistry*; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D018736:DNA Adducts; D003839:Deoxyadenosines; D004101:Dihydroxydihydrobenzopyrenes; C071371:dibenzo(a,l)pyrene 11,12-dihydrodiol; D004247:DNA