Prediction of the binding mode of imidacloprid and related compounds to house-fly head acetylcholine receptors using three-dimensional QSAR analysis

The binding activity of imidacloprid and related compounds to nicotinic acetylcholine receptors (nAChR) of house flies was measured by use of radioactive α‐bungarotoxin as a ligand. Variations in the activity were examined three‐dimensionally using comparative molecular field analysis (CoMFA). The CoMFA results suggest that one conformer among the four stable ones is active and provide support for one of the proposed binding models for this class of compound, in which the nitrogen atom of the pyridine ring and the nitrogen atom at the 1‐position of the imidazolidine ring interact with the hydrogen‐donating and electron‐rich sites of nAChR, respectively. The CoMFA field map showed that the nitroimino moiety and a portion of the imidazolidine ring were mainly surrounded by a sterically and electrostatically sensitive region of nAChR. © 1998 Society of Chemical Industry