Linear dichroism properties and orientations of different ultraviolet transition moments of benzo[a]pyrene derivatives bound noncovalently and covalently to DNA.
Linear dichroism and absorption methods are used to study the orientations of transition moments of absorption bands of polycyclic aromatic epoxide derivatives which overlap with those of the DNA band in the 240-300 nm region. Both the short and long axes of the pyrene residues of 1-oxiranylpyrene (1-OP) and the (+) and (-) enantiomers of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) noncovalently bound to double-stranded native DNA are oriented approximately perpendicular to the axis of the DNA helix, consistent with intercalative modes of binding. The covalent binding of these three epoxide derivatives to DNA is accompanied by reorientations of both the short and long axes of the pyrene residues. Covalent adducts derived from the highly mutagenic (+)-anti-BPDE are characterized by tilts of the short axis within 35 degrees or less, and of the long axis by more than 60-80 degrees, with respect to the planes of the DNA bases. In the adducts derived from the binding of the less mutagenic (-)-anti-BPDE and 1-OP epoxide derivatives to DNA, the long axes of the pyrenyl rings are predominantly oriented within 25 degrees of the planes of the DNA bases; however, in the case of the (-) enantiomer of BPDE, there is significant heterogeneity of conformations. In the case of the 1-OP covalent DNA adducts, the short axis of the pyrene ring system is tilted away from the planes of the DNA bases, and the pyrene ring system is not intercalated between DNA base-pairs as in the noncovalent complexes. The stereochemical properties of the saturated 7,8,9,10-ring in BPDE, or the lack of the 7 and 8 carbon atoms in 1-OP, do not seem to affect noncovalent intercalative complex formation which, most likely, is influenced mainly by the flat pyrenyl residues. These structural features, however, strongly influence the conformations of the covalent adducts, which in turn may be responsible for the differences in the mutagenic activities of these molecules.
Roche
C J
CJ
Chemistry Department, New York University, NY 10003.
Geacintov
N E
NE
Ibanez
V
V
Harvey
R G
RG
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001564:Benzo(a)pyrene; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; D011721:Pyrenes; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; D011721:Pyrenes; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; C043956:1-oxiranylpyrene