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,获得了它们的前线轨道能(EHOMO、ENHOMO、ELUMO、ENLUMO等)、原子电荷(Qi)、摩尔熵(Sm)、偶极矩(μ)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n AChRs、哺乳动物α4β2亚型的亲和力常数(p KD、p KA)分别与ELUMO、QW、QF、QN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模型推断了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。基于分子17,设计出4种经结构修饰后对果蝇n AChRs亲和力显著提高的重氮乙烷新烟碱类分子(分别是分子27,28,30和31),希望能得到实验的证实。
Based on the B3 LYP /6-311 G,the quantum chemical calculation of DFT method had been used to study the electronic structures and properties of 20 kinds of neonicotinoid insecticides. The structural parameters and the physical properties including the energy of frontier orbital( EHOMO、ENHOMO、ELUMO、ENLUMOetc.),the net charge of atoms in molecules( Qi),molar entropy Smand dipole moment μ had been obtained. It was found that there are good linear relationships between the experimental agonistic activity data( p KD,p KA) for the insecticides to the Drosophila n AChRs or Mammal α4β2and the calculated parameters such as ELUMO,QW,QF,and QNof the molecules respectively by leaps-and-bounds regression analysis. The established two QSAR( quantitative structure-activity relationship) models had good stability and predictability based on the results from Rcv2,Rcv- 42 of leave-one or fourout cross-validation,VIF,tα /2. The possible mechanisms for the inhibition of neonicotinoid insecticides had been proposed according to two QSAR models. Further studies indicated that the agonistic activities for the modified molecules on insecticides could be improved,if the structural modifications were 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 molecule 17,four kinds of neonicotinoid molecules( 27,28,30 and 31) had been designed by the structural modifications to improve their biological activities( to Drosophila n AChRs) obviously,which were expected to be confirmed experimentally.
出处
《化学通报》
CAS
CSCD
北大核心
2015年第1期55-62,共8页
Chemistry
基金
国家自然科学基金项目(21075138)
环境模拟与污染控制国家重点联合实验室开放基金项目(13K02ESPCT)
徐州市科技局基金项目(XM13B111)资助
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
Neonicotinoid insecticide
Drosophila
Mammal
Nicotine acetylcholine receptors(nAChRs)
Agonistic activity data
Density functional theory
Quantitative structure-activity relationship
Structural modification
