Structure-Toxicity Relationships for the Effects to Tetrahymena pyriformis of Aliphatic, Carbonyl-Containing, ,
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- 作者：T. Wayne Schultz ; Tatiana I. Netzeva ; David W. Roberts ; and Mark T. D. Cronin
- 刊名：Chemical Research in Toxicology
- 出版年：2005
- 出版时间：February 2005
- 年：2005
- 卷：18
- 期：2
- 页码：330 - 341
- 全文大小：141K
- 年卷期：v.18,no.2(February 2005)
- ISSN：1520-5010
文摘
Toxicity data for 82 aliphatic chemicals with an 
,
-unsaturated substructure were compiled.Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairmentassay. Toxic potency [log(IGC50-1)] for most of these chemicals was in excess of baseline narcosisas quantified by the 1-octanol/water partition coefficient (log Kow). The toxicity of the ,-unsaturated aldehydes was modeled well by log Kow in conjunction with the sum of partialcharges on the vinylene carbon atoms (QC4 + QC3) and the energy of the lowest unoccupiedmolecular orbital (Elumo). These electronic descriptors were also successful at modeling thetoxicity of ,-unsaturated ketones. The toxicity of a range of acrylates was constant withinabout 0.2 of a log unit. Conversely, the toxicity of methacrylates and esters containing thevinylene group varied considerably and was explained by their hydrophobicity. The comparisonof the quantitative structure-activity relationship (QSAR) for the methacrylates and esterswith that for non-polar narcosis showed little significant difference and hence suggested thatsubstitution on the carbon-carbon double bond in the methacrylates and vinylene unsaturatedesters does not enhance toxicity over that of baseline. Substitution on the carbon-carbon doublebond in the ,-unsaturated aldehydes resulted in toxicity that was similar to that for saturatedderivatives. Although an excellent hydrophobicity-dependent QSAR was developed for the esterscontaining ethynylene group, these compounds are considered to act as Michael-type acceptors.Attempts to combine different groups of Michael-type acceptors into a single QSAR, based onmechanistically derived descriptors, were unsuccessful. Thus, the modeling of the toxicity ofthe ,-unsaturated carbonyl domain is currently limited to models for narrow subdomains.
,-unsaturated substructure were compiled.Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairmentassay. Toxic potency [log(IGC50-1)] for most of these chemicals was in excess of baseline narcosisas quantified by the 1-octanol/water partition coefficient (log Kow). The toxicity of the ,-unsaturated aldehydes was modeled well by log Kow in conjunction with the sum of partialcharges on the vinylene carbon atoms (QC4 + QC3) and the energy of the lowest unoccupiedmolecular orbital (Elumo). These electronic descriptors were also successful at modeling thetoxicity of ,-unsaturated ketones. The toxicity of a range of acrylates was constant withinabout 0.2 of a log unit. Conversely, the toxicity of methacrylates and esters containing thevinylene group varied considerably and was explained by their hydrophobicity. The comparisonof the quantitative structure-activity relationship (QSAR) for the methacrylates and esterswith that for non-polar narcosis showed little significant difference and hence suggested thatsubstitution on the carbon-carbon double bond in the methacrylates and vinylene unsaturatedesters does not enhance toxicity over that of baseline. Substitution on the carbon-carbon doublebond in the ,-unsaturated aldehydes resulted in toxicity that was similar to that for saturatedderivatives. Although an excellent hydrophobicity-dependent QSAR was developed for the esterscontaining ethynylene group, these compounds are considered to act as Michael-type acceptors.Attempts to combine different groups of Michael-type acceptors into a single QSAR, based onmechanistically derived descriptors, were unsuccessful. Thus, the modeling of the toxicity ofthe ,-unsaturated carbonyl domain is currently limited to models for narrow subdomains.