Quantitative Structure–activity Relationship of a Series of N-Aryl O-Aryl Phosphoramidate Insecticides

Abstract

Abstract-A series of O-ethyl O-aryl N-aryl phosphoramidates was prepared and examined for housefly contact toxicity and acetylcholinesterase (AChE) inhibition. Results showed a moderate toxicity and enzyme inhibition effect. These biological properties correlated to Hammett sigma constants in the direction of increasing activity with increasing electron donation of the substituents on either the phenolic or anilinic ring of the phosphoramidates. These correlations suggest the formation of a positive charge on the phosphorus atom that is stabilized by electron-donating groups. This result invokes the mechanism of the electropholic attack of phosphorus on a nucleophilic center of AChE. The moderate toxicity of phosphoramidates is attributed to the reduction of the positive charge on the phosphorus atom by the effect of the neighboring nitrogen atom during the course of the enzyme-inhibitor interaction and hence decreasing the inhibition effect. Mass spectra of these compounds are also discussed in some detail.