Quantitative structure-activity relationship of a series of N-aryl O-aryl phosphoramidate insecticides

A series of O-ethyl O-aryl N-aryl phosphoramidates was prepared and examine d for housefly contact toxicity and acetylcholinesterase (AChE) inhibition. Results showed a moderate toxicity and enzyme inhibition effect. These bio logical properties correlated to Hammett sigma constants in the direction o f increasing activity with increasing electron donation of the substituents on either the phenolic or anilinic ring of the phosphoramidates. These cor relations suggest the formation of a positive charge on the phosphorus atom that is stabilized by electron-donating groups. This result invokes the me chanism of the electropholic attack of phosphorus on a nucleophilic center of AChE. The moderate toxicity of phosphoramidates is attributed to the red uction of the positive charge on the phosphorus atom by the effect of the n eighboring nitrogen atom during the course of the enzyme-inhibitor interact ion and hence decreasing the inhibition effect. Mass spectra of these compo unds are also discussed in some detail.