1-[N-(2-Chloro-5-thiazolylmethyl)]-2-nitromethylene-imidazolidine (NMI) is a very potent insecticide and is 6-fold more effective than imidacloprid (IMI) in displacing [3H]IMI from its binding site in the house fly acetylcholine (ACh) receptor (AChR). NMI differs from IMI in two isosteric replacements, i.e., 2-chloro-5-thiazolyl (CT) for 6-chioro-3-pyridinyl (CP) and nitromethylene for nitroimine. The CP and CT moieties in this series confer almost equivalent potency and binding properties allowing intercomparisons based on the nitromethylene and nitroimine substituents. [3H]NMI (55 Ci/mmol) was prepared from 2-chloro-5-(carbethoxy)thiazole by reducing with lithium aluminum tritide to the alcohol which was converted to the chloromethyl derivative and then coupled with ethylenediamine followed by reaction with 1,1-bis(methylthio)-2-nitroethylene. Binding parameters in house fly head membranes treated with Triton X-100 are very similar for [3H]NMI and [3H]IMI, each with a single saturable specific binding site of Kd = 1.2 nM and Bmax = 853-897 fmol/mg protein, and there are also similar initial rates of association and dissociation for the two radioligands. However, there is a significant difference in the Hill coefficient with 1.4 ± 0.06 for NMI and 1.0 ± 0.1 for IMI. Without Triton X-100 treatment, there are both low and high affinity binding components for [3H]IMI but only a low affinity one for [3H]NMI. Competing ligands are less effective at displacing [3H]NMI than [3H]IMI, e.g., 9-fold for ACh (with paraoxon to inhibit acetylcholinesterase), 40-fold for carbachol, and 2- to 6-fold for the nicotinic agents (-)-nicotine and α-bungarotoxin. The enhanced insecticidal activity and receptor potency of NMI compared with IMI may be associated with its higher apparent cooperativity facilitating disruption of the AChR.
All Science Journal Classification (ASJC) codes
- Agronomy and Crop Science
- Health, Toxicology and Mutagenesis