title: Correlations of nitrenium ion selectivities with quantitative mutagenicity and carcinogenicity of the corresponding amines.
abstract: There is a correlation (r(adj)(2) = 0.5491-0.6338) of quantitative mutagenicity, log m, for a series of heterocyclic (HCAs) and carbocyclic (AAs) aromatic amines in Salmonella typhimurium TA 98 (18 amines) and TA 100 (15 amines) vs log S, the log of the azide/solvent selectivity of the corresponding nitrenium ion. Monocyclic aromatic amines, MAAs, are less mutagenic than other amines of similar log S. Multiple variable linear regression analysis led to a two parameter regression model, significant at the 95% confidence level for both variables, that includes log S and a ring index variable, I(rings), that is 0 for MAAs and 1 for all other amines. These models have r(adj)(2) = 0.8448 for TA 98, and 0.8927 for TA 100. Inclusion of a third variable, Clog P, increases r(adj)(2) to 0.8913 for TA 98 and 0.9011 for TA 100. This model is significant at the 95% confidence level for all variables for TA 98, but only for two of the three variables for TA 100. The confidence level is 80% for Clog P in TA 100. Quantitative carcinogenicity data in mice and rats are more weakly correlated with log S (r(adj)(2) = 0.5357 for 12 amines in mice, r(adj)(2) = 0.4216 for 10 amines in rats). Several two parameter regression models, all containing Clog P and one containing log S, adequately correlate the mouse data.
authors.affiliation: Department of Chemistry, Miami University, Oxford, Ohio 45056, USA. novakm@muohio.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Novak
authors.forename: Sridharan
authors.initials: S
authors.lastname: Rajagopal
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D001386:Azides / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000633:toxicity; D007477:Ions; D051379:Mice; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity*; D009584:Nitrogen / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013816:Thermodynamics
chemical_list: D000588:Amines; D001386:Azides; D002273:Carcinogens; D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D007477:Ions; D009153:Mutagens; D009584:Nitrogen