Paper Info
Title
Response-Surface Analyses for Toxicity to Tetrahymena pyriformis: Reactive Carbonyl-Containing Aliphatic Chemicals
Abstract
A response-plane has been developed with Tetrahymena pyriformis population growth impairment toxicity data [log 1/50% growth inhibitory concentration (IGC(50))], the 1-octanol/water partition coefficient (log K-ow), and the energy of the lowest unoccupied molecular orbital (E-lumo). A statistically robust plane [log 1/IGC(50) = 0.530 (log K-ow) - 0.890 (E-lumo) - 0.271, n = 50, s = 0.295, r(2) = 0.855, F = 145] was found for reactive carbonyl-containing aliphatic chemicals. These compounds had a variety of electrophilic mechanisms of action and included aldehydes acting as Schiff-base formers, alpha,beta-unsaturated aldehydes and alpha,beta-unsaturated ketones acting as Michael-type accepters, and selected alpha-diones acting as selective binders to arganine residues; gamma-diones acting as selective binders to tubulin; and beta-diones with unknown mechanisms of action. Outliers to this model broadly fell into two groups: small reactive molecules (e.g., acrolein) that were more toxic than predicted and molecules in which the reactive center was sterically hindered by an alkyl group (e.g., 2,4-dimethyl-2,6-heptadienal) that were less toxic than predicted.
Year
DOI
Venue
1999
10.1021/ci9800965
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
DocType
Volume
Issue
Journal
39
2
ISSN
Citations 
PageRank 
0095-2338
3
0.85
References 
Authors
0
2
Name
Order
Citations
PageRank
T. Wayne Schultz1121.66
Mark T. D. Cronin23110.12