Structure–activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds^‖

‖Presented at the 12th International Workshop on Quantitative Structure--Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.

Abstract

Using abiotic thiol reactivity (EC₅₀) and Tetrahymena pyriformis toxicity (IGC₅₀) data for a group of halo-substituted ketones, esters and amides (i.e. S_N2 electrophiles) and related compounds a series of structure–activity relationships are illustrated. Only the α-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose α-halo-carbonyl compounds to be more reactive than non-α-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 α-halo-carbonyl-containing compounds with different β-alkyl groups shows the greater the size of the β-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: ; n = 19, s = 0.250, r ² = 0.926, r ²(pred) = 0.905, F = 199, Pr > F = 0.0001.

‖Presented at the 12th International Workshop on Quantitative Structure--Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.

Keywords:

• Structure–activity relationships
• Halogenated carbonyl chemicals
• Abiotic thiol reactivity
• Tetrahymena pyriformis toxicity

Acknowledgments

This work was supported in part by the US Army Medical Research and Material Command under contract No. W81XWH-050C-0017 and a grant from Veith Scientific Designs, LLC. The views, opinions and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy or decision unless otherwise so designated by other documentation.

Notes

‖Presented at the 12th International Workshop on Quantitative Structure--Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.