RP6 Chiral Chemistry: Toxicology of Environmental Contaminants and Phase Transfer
Thursday, 17 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(NIL-1117-822313) Acetylcholinesterase Inhibition of Chiral Organophosphorus Insecticides.

Nillos, M¹, Schlenk, D¹, Gan, J¹, ¹ University of California - Riverside, Riverside, CA, USA

ABSTRACT- A number of organophosphorus pesticides (OPs), although mainly marketed and used in racemic form, have chiral centers. OPs are among the most commonly used pesticides because they inhibit acetylcholinesterase (AChE) in insects, by phosphorylation and phosphonylation of the enzyme. Studies on the differences in bioactivity between enantiomers of a chiral pesticide are still limited. Enantioselective biological recognition of enantiomers is often observed in and is determined by the stereochemistry of the biological system (e.g. macromolecules such as enzymes, cellular receptors or molecules involved in membrane transport). The specific stereochemistry in these systems can result in the preferential interaction with one of the enantiomers over the other. Prior acute toxicity studies with D.magna suggest that the (-) enantiomer of trichloronate, crotoxyphos, fonofos and profenofos was consistently more active than the (+) enantiomer. This study measured AChE inhibition by individual enantiomers of each chiral OP. Resolution and isolation of OP enantiomers were carried out on HPLC using a chiral column. Preliminary results from in vitro AChE inhibition tests with D. magna suggest a 32% reduction in activity of AChE exposed to 100 ppb profenofos racemate, while exposure to 300 ppb (-) enantiomer of profenofos resulted in approximately 74% reduction in activity but no significant reduction with the (+) enantiomer of the same concentration. These results indicate significant differences in toxicity between the (-) and (+) enantiomers that is consistent with acute toxicity results.

Key words: Acetylcholinesterase, Chiral, Organophosphorus