structure/activity relationships of pyrethroid insecticides. 1. A novel approach based upon the use of multivariate QSAR and computational chemistry

The structure/activity relationships of substituted benzyl (1RS)‐transcyclopropane‐1‐carboxylate insectieides have been investigated by a combination of multivariate statistical techniques and molecular modelling. Quantum and molecular mechanics were used to calculate a set of seventy descriptors to represent the molecular properties of the series. These can be summarised by eight uncorrelated factors which describe the associations between the seventy descriptors with little loss of information. The neurotoxicities, knockdown and killing activities of the compounds are associated with the same three physicochemical factors, suggesting that common molecular features are required for these different responses. In this series, high biological potency is conferred by the presence of a partial positive charge at a meta carbon in the benzyl ring of the alcohol moiety, small nucleophilic superdelocalisabilities on the carbonyl carbon and oxygen atoms of the ester linkage, and chlorosubstituents subtended by the terminal carbon atom of the vinyl side chain at C3 of the cyclopropane ring. An additional property related to the nucleophilic superdelocalisabilities of the ortho and meta carbons of the benzyl ring is required for knockdown activity.