Abiotic sulfhydryl reactivity: a predictor of aquatic toxicity for carbonyl-containing alpha,beta-unsaturated compounds.
A diverse series of aliphatic alpha,beta-unsaturated esters, ketones, and aldehydes were evaluated for reactivity with the model nucleophile sulfhydryl group in the form of the cysteine residue of the tripeptide glutathione; the reactive end point (RC50) was then related to aquatic toxicity (IGC50) assessed in the Tetrahymena pyriformis population growth impairment assay. The substructure specific to all tested reactive substances, an olefin conjugated to a carbonyl group, is inherently electrophilic and conveys the potential to act by way of Michael-type nucleophilic addition. All such unsaturated compounds are inherently acutely toxic. However, their toxicity is difficult to model with conventional descriptors since toxicity is independent of both hydrophobicity and molecular orbital electrophilicity but dependent on the specific molecular structure. While methacrylates typically did not attain an RC50 value at saturation, a linear relationship [log (IGC50(-1)) = 0.936[log (RC50(-1))] + 0.508, where n = 41, r2 = 0.846, q2 = 0.832, s = 0.35, F = 214, and Pr > F = 0.0001] was observed between aquatic toxicity and reactivity for the other carbonyl-containing alpha,beta-unsaturated chemicals.
Yarbrough
Jason W
JW
Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, Knoxville, Tennessee 37996-4543, USA.
Schultz
T Wayne
TW
D000171:Acrolein / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry / Q000633:toxicity; D000465:Algorithms; D000818:Animals; D003627:Data Interpretation, Statistical; D004952:Esters / Q000737:chemistry / Q000633:toxicity; D005978:Glutathione / Q000737:chemistry / Q000633:toxicity; D007659:Ketones / Q000737:chemistry / Q000633:toxicity; D007700:Kinetics; D020366:Methylmethacrylate / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry* / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013769:Tetrahymena pyriformis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D000447:Aldehydes; D004952:Esters; D007659:Ketones; D009930:Organic Chemicals; D013438:Sulfhydryl Compounds; D020366:Methylmethacrylate; D000171:Acrolein; D005978:Glutathione