MOLECULAR MECHANISM FOR SELECTIVE TOXICITY OF NICOTINOIDS AND NEONICOTINOIDS

The binding study on nicotinoids, neonicotinoids and the related compo unds using [H-3]alpha-bungarotcsin and [H-3]nicotine as probes reveale d that binding to the recognition site of nicotinic acetylcholine rece ptor (nAChR) in insects requires the molecules to have 3-pyridylmethyl amino moiety, while high ionization in vertebrates. When [H-3]phencycl idine was used as a probe for the ion channel opening of Torpedo nAChR , it was indicated that high ionization of the molecule is important t o be agonistic, although the presence of 3-pyridylmethylamino moiety i s preferred. N-15 NMR Of the amino nitrogen atom of nicotinoids and th e corresponding one of neonicotinoids indicated that the latter was fa r deshielded as compared with the former. The result implies that the unshared electron pair on the concerned nitrogen atom is delocalized b y the presence of strong electron-withdrawing group and the nitrogen a tom becomes partially positive. Such nitrogen is enough to interact wi th the insect nAChR, but not with the vertebrate one. The overall resu lts explain why nicotine is highly toxic to mammals and rather limited in insecticidal activity, whereas imidacloprid is highly insecticidal and low in mammalian toxicity.