Quantitative structure-toxicity relationships for 80 chlorinated compounds using quantum chemical descriptors

The acute toxicity to Photobacterium phosphoreum (MicrotoxTM test) of a set of 80 chlorinated compounds, containing aliphatics, benzenes, toluenes, phenols and anilines, was investigated using ‘Theoretical Linear Solvation Energy Relationship’ (TLSER) parameters. Quantative Structure-Activity Relationships (QSARs) were developed for chemical and toxicological subsets. Molecular volume (Vmc) revealed to be the most important TLSER descriptor. For the complete data set and for the phenols the TLSER descriptors are superior to log P alone. In the case of the phenols this is related to electronic information being inherent in the electrostatic parameter q−, which is correlated to the pKa of the compounds. For the benzenes a quadratic term in Vmc was very useful for the description of the toxicity. Many of the chlorinated aliphatics do not fit the narcosis I QSAR. Enhanced chemical reactivity due to the chlorine substitution may lead to activation or biodegradation of these compounds. The attempt to establish naccosis II QSARs for the polar narcotic chloroanilines and -phenols was unsuccessful. It seems that some chloroanilines interact directly with the bioluminescene system of P. phosphoreum. The authors emphasize that the concept of baseline narcosis implies that the ‘pure’ narcosis II mechanism decreases with increasing log P. The site of toxic action for narcosis II is therefore thought to be hydrophilic. Uncoupling of oxidative phosphorylation seems to play a minor role in the photobacterium than it does in fish. Reasons for this may be the ability of bacteria to crack and detoxify aromatic rings or the relative robustness of oxidative phosphorylation in bacteria.