Carcinogenesis, Vol. 20, No. 8, 1549-1554,
August 1999
© 1999 Oxford University Press
Carcinogenesis |
Three-dimensional structure of anti-5,6-dimethylchrysene-1,2-dihydrodiol-3,4-epoxide: a diol epoxide with a bay region methyl group
1 The Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111 and
2 American Health Foundation, 1 Dana Road, Valhalla, NY 10595, USA
The three-dimensional structure of a dihydrodiol epoxide of 5,6-dimethylchrysene was elucidated by X-ray diffraction techniques. The effects of the steric overcrowding by the 5-methyl group in the bay region of this compound are described. The carbon atom of the 5-methyl group is found to lie out of the plane of the aromatic system, thereby avoiding the nearer C-H group of the epoxide ring; this C-H hydrogen atom is pushed in the opposite direction. As a result, the molecule is distorted so that the relative orientations of the epoxide group and the aromatic ring systems are very different for the diol epoxides of (nearly planar) benzo[a]pyrene (studied by Neidle and co-workers) and (distorted) 5,6-dimethylchrysene (described here). The main effect of the 5-methyl group is to change the relative angle between the epoxide-bearing ring (the site of attack when the diol epoxide acts as an alkylating agent) and the aromatic ring system (which is presumed to lie partially between the DNA bases in the DNA adduct that is about to be formed). This may favor some specific alkylation geometry.
Abbreviations: BaP, benzo[a]pyrene; 5,6-diMeC, 5,6-dimethylchrysene; PAH, polycyclic aromatic hydrocarbon
3 To whom correspondence should be addressed Email: jp_glusker{at}fccc.edu