Structure-Toxicity Relationships For Alkanones and Alkenones

Abstract

The relative toxicity (log IGC⁻¹ ₅₀) of 54 selected alkanones, both aliphatic and aromatic, as well as, alkenones and alkynones was evaluated in the static Tetrahymena pyriformis population growth assay. Excess toxicity, an indicator of bioreactivity, was associated only with the α-β unsaturated alkenones and alkynones. Moreover, the alkynones were found to be more toxic than corresponding alkenones. A high quality 1-octanol/water partition coefficient (log K_ow) dependent structure-toxicity relationship, log IGC⁻¹ ₅₀ = 0.86 (log K_ow) – 2.27; r² = 0.955, was developed for alkanones. This QSAR represented the nonpolar narcosis mechanism of toxic action. Toxicity of alkenones was predicted by the highest-occupied-molecular-orbital energy (HOMO), log IGC⁻¹ ₅₀ = −3.474 (HOMO) −35.357; r² = 0.897, and the difference between HOMO and the lowest-unoccupied-molecular-orbital energy (LUMO), log IGC⁻¹ ₅₀ = −3.559 (HOMO-LUMO gap) − 36.106; r² = 0.903. The α-β unsaturated ketones are considered soft electrophiles. Moreover, the toxicity of the aliphatic alkanones and alkenones was predicted by log K_ow and LUMO, log IGC⁻¹ ₅₀ = 0.69 (log K_ow) − 2.55 (LUMO) + 0.05; r² = 0.852.

Key Words:

• Structure-toxicity
• ketones
• narcosis
• soft electrophile
• Tetrahymena pyriformis