Water bridges are essential to neonicotinoids: Insights from synthesis,bioassay and molecular modelling studies

作     者：Chengchun Zhu Guanglong Li Keya Xiao Xusheng Shao Jiagao Cheng Zhong Li 

作者机构：Shanghai Key Laboratory of Chemical Biology School of Pharmacy East China University of Science and Technology Shanghai Collaborative Innovation Center for Biomanufacturing Technology 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2019年第30卷第1期

页      面：255-258页

核心收录：

学科分类：07[理学] 0703[理学-化学] 

基　　金：the financial supports from the National Natural Science Foundation of China (Nos. 21572059, 21172070) Innovation Program of Shanghai Municipal Education Commission (No. 201701070002E00037) 

主　　题：Neonicotinoids Water bridge Insecticidal activity Cyano group Molecular design 

摘      要：Water-bridged H-bonds have been observed in many cases of ligand-receptor recognitions. To explore the roles of water bridges in the binding of neonicotinoids with receptors, twenty-four neonicotinoid compounds with nine fragments, including 1 H-1,2,3-triazole, CN, COOMe, CONHNH_2, CONHMe, NO_2,NH_2, NHCOMe and NHCSNH_2 were synthesized and evaluated, of which, compounds with cyano group showed the best activities against Aphis craccivora. Accordingly, the cyano group is the optimal fragment mimicking the water bridge. Two cyano-substituted cis-nitromethylene compounds display good insecticidal activities, whereas the LC_(50) values are lower than those of their corresponding *** study showed that the cyano group acts only as H-bond acceptor, while the water bridge can act as both donor and acceptor. It revealed that the water bridge might be stable in the active site and was not suitable to be replaced by other groups. The findings illustrated that the water bridge is necessary for high insecticidal activities of neonicotinoids, which should be also helpful in better understanding the binding mode of neonicotinoids.