Neonicotinoids binding models

The binding model is also a critical issue for the design and structure-activity relationship of new derivatives. Here, ab initio quantum chemical calculation was used for the investigation of nonbonded bindings between neonicotinoids and key residues of nAChR. 

Figure 2. The alternative binding model between neonicotinoids and nAChR.

For example, in 1970 a useful nicotinic pharmacophore model was already described by Beers and Reich and subsequently improved by Sheridan et al. [103]. Starting from different models a distance from the onium group to a point on the van der Waals surface of the H-bond acceptor of 5.9 A was common to several ligands. Up to now three binding models of neonicotinoids have been proposed (cf Fig. 29.1.2) [104]. 

Generally, the open-chain neonicotinoids are less lipophilic than the corresponding neonicotinoids with a ring structure (Chapters 29.2.2 and 29.2.3). Based on CoMFA results, a binding model for imidacloprid (11) has been described. 

Acetylcholine Binding Protein, Chicken a4 Subunit, Chicken (32 Subunit, Drosophila mdanogasterDal Subunit, Homology Modeling, Loop D, Neonicotinoid, Nicotinic Acetylcholine Receptor, Two-Electrode Voltage-Clamp... 

Neonicotinoids target nicotinic acetylcholine receptors as is mostly known from studies with imidacloprid and conveniently sized lab model insects real target pests have not yet been used for technical reasons. Hence, conclusions, especially those on receptor sensitivity, should be taken with care. On the other hand, radioligand binding studies, which usually do not impose technical hurdles, have been widely performed with neonicotinoids using membranes from target and non-target insects. 

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