Synthesis of alkylene-tethered bis-imidacloprid derivatives as highly insecticidal and nerve-exciting agents with potent affinity to (3H)imidacloprid-binding sites on nicotinic acetylcholine receptor

"Bivalent molecules of bis-imidacloprid with 2-10 alkylene tethers as well as tethers containing an ethenylene, ethynylene, phenylene and oxide joint were prepared. These dimeric chloronicotinyl mole-cules were highly insecticidal against American cockroaches on injection at 2-30 nanomolar doses. The minimum lethal dose of the most potent hexamethylene derivative was close to that of imidacloprid, and the potency was augmented up to about thirty-five-fold following pretreatment with metabolic inhibitors, while the binding affinity to [sup3 H] imidacloprid-binding sites on the nicotinic acetvlcholine receptor was weaker than that of imidacloprid by a factor of 160. The hexamethylene derivative elicited impulses in cockroach central nerves with an initial excitation and subsequent block at a potency comparable to imidacloprid."