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Structure-toxicity relationships for alkanones and alkenones
T W Schultz1, G D Sinks, R S Hunter
1College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
SAR and QSAR in Environmental Research
|January 1, 1995
Summary
This study evaluated the toxicity of various ketones using the Tetrahymena pyriformis assay. Unsaturated ketones showed higher toxicity, with alkynones being more potent than alkenones.
Area of Science:
- Environmental toxicology
- Computational chemistry
- Chemical risk assessment
Background:
- Ketones, including alkanones, alkenones, and alkynones, are prevalent in various industrial and environmental settings.
- Understanding their ecotoxicity is crucial for assessing environmental risks and developing predictive models.
- Previous studies have explored structure-activity relationships for some organic compounds, but a comprehensive analysis of diverse ketone classes is needed.
Purpose of the Study:
- To evaluate the relative toxicity of 54 selected alkanones, alkenones, and alkynones using a Tetrahymena pyriformis population growth assay.
- To identify structure-toxicity relationships and mechanisms of action for different ketone classes.
- To develop quantitative structure-activity relationship (QSAR) models for predicting ketone toxicity.
Main Methods:
- Static Tetrahymena pyriformis population growth assay was employed to determine relative toxicity (log IGC-1(50)).
- Evaluated 54 diverse ketone compounds, including aliphatic and aromatic alkanones, alkenones, and alkynones.
- Developed QSAR models based on physicochemical properties like 1-octanol/water partition coefficient (log Kow) and molecular orbital energies (HOMO, LUMO).
Main Results:
- Excess toxicity, indicative of bioreactivity, was observed specifically in alpha-beta unsaturated alkenones and alkynones.
- Alkynones exhibited higher toxicity compared to their corresponding alkenones.
- A robust QSAR model for alkanones was developed based on log Kow (r2 = 0.955), indicating a nonpolar narcosis mechanism.
- Toxicity of alkenones was effectively predicted by HOMO and HOMO-LUMO gap energies (r2 = 0.897 and r2 = 0.903, respectively).
- A combined QSAR model using log Kow and LUMO predicted the toxicity of aliphatic alkanones and alkenones (r2 = 0.852).
Conclusions:
- Alpha-beta unsaturated ketones act as soft electrophiles, contributing to their increased toxicity.
- The study successfully established distinct QSAR models for different ketone classes, highlighting varying mechanisms of toxicity.
- Predictive models based on log Kow and molecular orbital energies can accurately estimate ketone ecotoxicity, aiding in environmental risk assessment.