Relative stabilities of nitrenium ions derived from polycyclic aromatic amines. Relationship to mutagenicity.
The relative energetics of arylamine N-hydroxylation and N-O heterolysis (ArNH2----ArNHOH----ArNH+) for condensed systems of two, three and four rings were calculated using semiempirical AM1 molecular orbital theory. The overall thermodynamics of N-hydroxylation were almost insensitive to the structure of the amine while differences in the energetics of nitrenium ion formation varied from 0 to 35 kcal mol-1. Limited correlations between the latter and the experimental TA98 and TA100 mutagenicities of the amines are presented.
Ford
G P
GP
Department of Chemistry, Southern Methodist University, Dallas, TX 75275.
Herman
P S
PS
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D004355:Drug Stability; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry* / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000588:Amines; D009153:Mutagens; D011083:Polycyclic Compounds