title: Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds.
abstract: Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC50) data for a group of halo-substituted ketones, esters and amides (i.e. SN2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose alpha-halo-carbonyl compounds to be more reactive than non-alpha-halo-carbonyl compounds; in addition, the reactivity is reduced when the number of C atoms between the carbonyl and halogen is greater than one. Comparing reactivity among alpha-halo-carbonyl-containing compounds with different beta-alkyl groups shows the greater the size of the beta-alkyl group the lesser the reactivity. A comparison of reactivity data for 2-bromoacetyl-containing compounds of differing dimensions reveals little difference in reactivity. Regression analysis demonstrates a linear relationship between toxicity and thiol reactivity: log (IGC(50)(-1)) = 0.848 log (EC(50)(-1)) + 1.40; n=19, s=0.250, r2=0.926, r2(pred)=0.905, F=199, Pr > F=0.0001.
authors: Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, TN 37996-4543, USA.
authors: T W
authors: TW
authors: Schultz
authors: K E
authors: KE
authors: Ralston
authors: D W
authors: DW
authors: Roberts
authors: G D
authors: GD
authors: Veith
authors: A O
authors: AO
authors: Aptula
mesh_terms: D000577:Amides / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D004952:Esters / Q000737:chemistry / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000737:chemistry* / Q000633:toxicity*; D007659:Ketones / Q000737:chemistry / Q000633:toxicity; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000633:toxicity; D013769:Tetrahymena pyriformis / Q000187:drug effects; D018675:Toxicity Tests; D014873:Water Pollutants / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000577:Amides; D004952:Esters; D006846:Hydrocarbons, Halogenated; D007659:Ketones; D013438:Sulfhydryl Compounds; D014873:Water Pollutants