| 李鸣建,冯长君.化学通报,2015,78(1):55-62. |
| 新烟碱类杀虫剂生物活性的理论研究和结构修饰* |
| Theoretical Studies of Biological Activitiesof Neonicotinoid Insecticides and Structural Modification |
| 投稿时间：2014-03-17 修订日期：2014-04-22 |
| DOI： |
| 中文关键词: 新烟碱杀虫剂 果蝇 哺乳动物 烟碱型乙酰胆碱受体 亲和力常数 密度泛函理论 构效关系 结构修饰 |
| 英文关键词:neonicotinoid insecticide, Drosophila, Mammal, nicotine acetylcholine receptors (nAChRs), antibacterial activity data, density functional theory, quantitative structure–activity relationship, structural modification |
| 基金项目: |
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| 中文摘要: |
| 在B3LYP/6-311G基组水平下,运用密度泛函理论(DFT)的量子化学方法,对20种重氮乙烷新烟碱类杀虫剂分子的电子结构特征进行了研究,获得了它们的EHOMO、ENHOMO、ELUMO、ENLUMO、ΔE1(= ELUMO-EHOMO)、ΔE2(= ENLUMO - ENHOMO)、QC1-QC7、QN、QN1、QW、QB、QYJ、QF、QZ、Ev、E、Cv、μ和S等量化参数与物理性质。经最佳变量子集回归研究发现,重氮乙烷新烟碱类杀虫剂分子对果蝇nAChRs、哺乳动物α4β2亚型亲和力常数(pKD,pKA)分别与QN、QB、ELUMO、QW、QF、QZ、μ等参数具有良好的线性关系。逐一或逐四剔除交互验证以及VIF、tα/2检验,所建2个QSAR模型具有良好的稳健性及预测能力。根据2个QSAR模型建议重氮乙烷新烟碱类分子可能的杀虫机理。进一步研究发现,在重氮乙烷新烟碱类分子的吡啶环上的合适部位,选用不含复键的吸电子能力较强的取代基团对其进行结构修饰,有利于提高修饰后分子的生物活性。 基于第17号分子,设计出4种经结构修饰后对果蝇nAChRs亲和力显著提高的重氮乙烷新烟碱类分子(分别是第27,28,30和31号分子),希望能得到实验的证实。 |
| 英文摘要: |
| Based on the B3LYP/6-311G, the quantum chemical calculation of density functional theory(DFT) method set has been used to study the electronic structure and properties of 20 neonicotinoid insecticides. The structural parameters and the physical properties including the energy of highest occupied molecular orbital (EHOMO), energy of the next highest occupied molecular orbital(ENHOMO), lowest unoccupied molecular orbital(ELUMO), energy of the next lowest unoccupied molecular orbital (ENLUMO), ΔE1(= ELUMO-EHOMO), ΔE2(= ENLUMO - ENHOMO), QC1-QC7,QN, QN1, QW, QB,QYJ,QF,QZ, Ev,E,Cv,μ and S have been obtained. It is found that there are good linear relationships between the experimental agonistic activity data(pKD, pKA) for the insecticides to the Drosophila nAChRs or Mammal α4β2 and the calculated parameters such as QN, QB, ELUMO, QW, QF, QZ, μ of the molecules respectively by Leaps-and-Bounds regression analysis. The established two QSAR(quantitative structure–activity relationship) models have good stability and predictability based on the results from Rcv2, Rcv-42 of leave-one or four -out cross-validation, VIF, tα/2. The possible mechanisms for the inhibition of neonicotinoid insecticides have been proposed according to two QSAR models. Further studies indicate that the agonistic activities for the modified molecules on insecticides can be improved, if the structural modifications are carried out on the suitable positions of pyridine ring of neonicotinoid molecules by using the substituent groups with the electron-withdrawing ability but without double bonds. Based on the 5th molecules, four kinds of neonicotinoid molecules(27th, 28th, 30th and 31th) have been designed by the structural modifications to improve their biological activities (to Drosophila nAChRs) obviously, which are expected to be confirmed experimentally. |
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