Structural factors contributing to insecticidal and selective actions of neonicotinoids

Abstract

Nicotinoids and neonicotinoids are characterized by the presence of the 3‐pyridylmethylamine moiety in their structure. In the former, the amino nitrogen atom is ionized, while in the latter the corresponding nitrogen atom is not ionized but bears a partial positive charge. Both types of insecticides interact with nicotinic acetylcholine receptor (nAChR) of insect origin. The poor interaction of neonicotinoids with vertebrate nAChR was shown by its poor binding affinity to the nAChR from Torpedo electric organ and rat brain and poor activation with nAChR expressed in Xenopus oocytes. The full positive charge was essential to interact with the vertebrate nAChR, while the 3‐pyridylmethylamine moiety with a partial positive charge was enough to interact with the insect nAChR. For penetration into the insect central nervous system, hydrophobicity seemed to play an important role, as indicated by the binding of the injected compounds to the housefly head nAChR. The ionization reduced hydrophobicity and limited the penetration of nicotinoids, resulting in less insecticidal activity. Among neonicotinoids, nitromethylene type compounds, though far higher in binding affinity, were less hydrophobic than the corresponding nitroimine type, and the net result was better or inferior insecticidal activity. A chlorine atom at the 6 position of the 3‐pyridyl group found in commercialized neonicotinoids contributes to increased binding affinity and more importantly hydrophobicity, thus increasing insecticidal activity. N‐Me‐imidacloprid was found to be a propesticide of imidacloprid. Arch. Insect Biochem. Physiol. 37:24–32, 1998. © 1998 Wiley‐Liss, Inc.

Actions of imidacloprid, clothianidin and related neonicotinoids on nicotinic acetylcholine receptors of American cockroach neurons and their relationships with insecticidal potency

“…3,4) The insecticidal potency is influenced not only by the intrinsic actions on the targets, but also by accessibility to nAChRs and metabolism in insects. 5) To date, the nicotinic potencies of many neonicotinoids have been characterized using binding assays to examine the correlation between binding potency and insecticidal potency as well as to clarify the structure-activity relationship. [5][6][7][8][9][10][11] However, relatively few electrophysiological studies have been conducted for such purposes.…”

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

“…Acetamiprid has a higher Log P than nitroguanidine equivalents and replacing the 3 position in the imidazoline ring with sulphur also increases hydrophobicity (thiacloprid), this is predicted to enhance cuticle penetration and hence lepidopteran contact activity. 98) 2.1.5. Nitenpyram Nitenpyram is the only commercial neonicotinoid possessing a nitroenamine pharmacophore.…”

“…99) However, the improved photostability of nitroimino compounds makes them more suited for agrochemical use 46) and the higher hydrophilicity of nitroimino compounds has been suggested to increase transport to the target site, overcoming their slightly lower intrinsic potency. 36,98) 2.2. Thianicotinoyl compounds 2.2.1.…”

Interaction between pesticides and other factors in effects on bees

“…The olefin has higher not lower insecticidal activity than the parent (Nauen et al, 2001). However, species differences in metabolism exist as, in the house fly, PBO increased imidacloprid toxicity 10.7-fold while O-propyl-O-(2-propynyl)phenylphosphate (PPP) increased both imidacloprid and acetamiprid toxicity (Yamamoto et al, 1988).…”