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A novel halogen bond and a better-known hydrogen bond cooperation of neonicotinoid and insect nicotinic acetylcholine receptor recognition

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Abstract

Neonicotinoid insecticides target the insect nicotinic acetylcholine receptor (nAChR) and are highly effective against the piercing-sucking pests. To explore the molecular interaction mechanism between the neonicotinoids and the insect nAChR, some key neonicotinoid compounds were docked into Aplysia californica acetylcholine binding protein (Ac-AChBP), which serves as a suitable structural surrogate of the insect nAChR. The binding mode study showed that the hydrogen bond force between the electronegative pharmacophore of the neonicotinoids and Cys190NH of the target binding pocket is crucial to the high efficiency of the neonicotinoids. Increasing the coplanarity between the guanidine or amidine and the electronegative pharmacophore of the neonicotinoids could increase the Π-Π stacking effect with Tyr188 of the Ac-AChBP and thus enhance the insecticidal potency. The introduction of an azide group to the chloropyridine ring of the neonicotinoids would reduce its binding ability due to the disappearance of a novel halogen bonding interaction. A series of novel neonicotinoid molecules were designed based on the halogen bonding interaction and two compounds with 6-bromopyridine-3-yl and 6-(trifluoromethyl)-3-pyridinyl were found to be with potential insecticidal activities.

A new binding model between the neonicotinoids and the insect target nAChR with the hydrogen bond force, the π-π stacking effect and the halogen bond interaction is successfully generated by the Surflex-Dock algorithm. Two compounds with 6-bromopyridine-3-yl and 6-(trifluoromethyl)-3-pyridinyl are found to be good neonicotinoids candidates with potentially high activities

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Acknowledgments

This work was supported by the grants from the National Natural Science Foundation of China (30800719) and National Science & Technology Support Program in the 12th Five-year Plan of China (2011BAE06B05). The authors thank Mr. Fuheng Chen in China Agricultural University for writing assistance.

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Authors and Affiliations

  1. Department of Applied Chemistry, College of Science, Key Laboratory of Pesticide Chemistry and Application Technology, China Agricultural University, Beijing, 100193, People’s Republic of China

    Hongxia Duan, Weiwei Zhang, Jin Zhao, Xinling Yang & Shuhui Jin

  2. College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Desheng Liang

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  1. Hongxia Duan
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  2. Weiwei Zhang
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  3. Jin Zhao
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  4. Desheng Liang
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  5. Xinling Yang
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  6. Shuhui Jin
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Correspondence to Hongxia Duan or Shuhui Jin.

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Duan, H., Zhang, W., Zhao, J. et al. A novel halogen bond and a better-known hydrogen bond cooperation of neonicotinoid and insect nicotinic acetylcholine receptor recognition. J Mol Model 18, 3867–3875 (2012). https://doi.org/10.1007/s00894-012-1393-4

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  • DOI: https://doi.org/10.1007/s00894-012-1393-4

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