Thiamethoxam binding studies

Saturation binding studies revealed the following data for affinity (Kj) and binding capacity (Bmax) for thiamethoxam 13 and imidadoprid 8 with fresh membranes from M. persicae assayed at 2 °C ... 

Binding experiments revealed unusual properties of thiamethoxam at the target site (77). The optimal assay conditions to demonstrate thiamethoxam binding to aphid membranes are different and more strictly deflned than those for imidacloprid. Highest specific binding of thiamethoxam is observed at low assay temperature (2 C) with freshly prep ed membranes. Furthermore, preparations stored frozen prior to the assay are as good as fresh ones for studies with imidacloprid but not with thiamethoxam. 

Our studies with aphids clearly suggest that thiamethoxam, like the other examined neonicotoinoids, binds to nicotinic receptors. However, there are clear differences to the other commercial neonicotinoids as documented by a kinetic analysis of competition experiments. While thiamethoxam binds to receptors with nanomolar affinity, micromolar concentrations are required to displace imidacloprid. Further, the interaction between the two compounds is noncompetitive meaning that binding of thiamethoxam reduces the binding capacity of the receptor preparation for imidacloprid but not its affinity. Thiamethoxam shares this unusual mode of inhibition with other neonicotinoids (not commercialized) also featured by an W-Methyl group in die pharmacophore. In the competitive mode, displayed by the other commercial neonicotinoids, the capacity is unchanged, while the affinity is reduced. 

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