Molecular structures of the chemical carcinogens 7-chloromethylbenz(a)anthracene and 7-chloromethyl-12-methylbenz(a)anthracene.
The three-dimensional structures of two carcinogens, 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[ai1anthracene, have been determined by X-ray crystallographic techniques. Both compounds are carcinogenic and are believed to act by alkylating DNA. However, the first has a nonplanar ring system, whereas the second has a planar ring system. The nonplanarity of 7-chloromethyl-12-methylbenz[a]anthracene results from steric hindrance between a hydrogen atom of the 12-methyl group and a hydrogen atom on the [a] ring. This molecule cannot be made planar unless the 12-methyl group or the [a] ring is removed. It is concluded that the carcinogenic activity of these compounds does not correlate with planarity of the ring system. This implies that, if DNA is the critical target of attack by these carcinogens, complete intercalation of the aromatic ring system of the carcinogen between the bases of DNA is not a likely mechanism of carcinogenic action in this system of compounds. The results presented here and those of others are more consistent with a model for a common interaction of the carcinogens 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[a]anthracene with DNA, in which they alkylate the bases of DNA and then lie with their long axes approximately parallel to the helix axis, probably in the major groove.
D000478:Alkylation; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D003461:Crystallography; D004247:DNA; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D004247:DNA