DeWeese, A.D.; Schultz, T.W. Structure-Activity Relationships for Aquatic Toxicity to Tetrahymena: Halogen-Substituted Aliphatic Esters. Environ. Toxicol. 2001, 16, 1, 54–60.

Abstract

The toxicity of a series of 21 mono- and dihalogenated aliphatic monoesters has been evaluated using a Tetrahymena pyriformis population growth impairment assay. A structure-activity model has been developed for toxicity data (log(IGC50(-1))), using the 1-octanol/water partition coefficient (logKow) and the energy of the lowest unoccupied molecular orbital (ELUMO) as descriptors. A statistically robust plane (log of the inverse of the 50% growth inhibitory concentration (IGC50(-1)) = 0.34 logKow - 0.84 (ELUMO) + 0.04; n = 15, r2 = 0.85, s = 0.26, F = 33, Pr > F = 0.0001) was found for monohalogen-substituted derivatives. These substances are thought to exhibit toxicity via the soft electrophilic mode of toxic action. This toxicity is imparted by the leaving ability of the halogen, which is enhanced when it is placed in close proximity to the carbonyl group. This leaving ability allows haloesters, especially alpha-haloesters, to undergo an SN2, addition-elimination substitution electro(nucleo)philic reaction. Outliers to the above model broadly fell into two groups: small reactive molecules (e.g., propylbromoacetate) that were more toxic than predicted and molecules in which the reactive center was sterically hindered by an alkyl group (e.g., ethyl-2-bromoisovalerate), which were less toxic than predicted.