松香基噻吩杂环杀虫剂的光活化诱导作用机制研究

Based on requirements of agricultural sustainable development, the development of green botanical pesticide of high efficiency, low toxicity and residue becomes very urgent and important. In this proposal, natural product rosin is chosen as the main raw materials, and a series of rosin-based thiophene heterocyclic molecules with different link structures are designed and synthesized by active substructure combination method. Meanwhile, the photoactivated insecticidal activity of target compounds is evaluated. On the basis of the screening of insecticidal activity, the mechanism of photoinduced oxidation of rosin-based thiophene heterocyclic compounds combined with symptomatology, histopathology, molecular toxicology and electron spin resonance method is systematically studied. How the unique molecular structure of rosin to influence the synergism of photoactivated insecticidal activity is especially focused. Through the density functional theory, the regulation of photodynamic reaction of target site by the chiral center, space effect, charge distribution and energy changes induced by light activation of rosin-based thiophene heterocyclic compounds on the insecticidal activity is investigated. In addition, the quantitative relationship model of the rosin-based thiophene heterocyclic compounds corresponding to the photoactivated insecticidal activity is built. The binding mode and insecticidal action mechanism of rosin-based molecules with receptors would be revealed at the level of molecular and electronic structure. These theories obtained in this study would provide guidance in the further design of rosin-based botanical insecticides, thus achieving the higher value-added applications of rosin in bio-pesticide field.

基于农业可持续发展的需要，开发高效、低毒、低残留的绿色植物源农药就变得非常紧迫和重要。本课题以天然产物松香为主要原料，通过活性亚结构拼接原理制备系列新型松香基噻吩杂环杀虫剂，并进行光活化杀虫活性研究；在活性筛选的基础上，结合症状学、组织病理学、分子毒理学和电子自旋共振等手段对其光诱导氧化作用机理进行分析，着重考察松香的独特分子结构增效杀虫活性的光诱导氧化作用方式；通过密度泛函理论，研究药剂分子的手性中心、空间效应、电荷分布和能量变化等调控靶标位点的光动力学反应；建立松香基噻吩杂环分子对应于光活化杀虫活性的定量关系模型，从分子、电子的结构水平进一步揭示药剂和受体的结合方式及作用机制。通过上述研究，可为新型高效松香基光活化杀虫剂的设计合成提供理论指导，并为松香在生物农药领域的高值化利用奠定基础。

本项目从化学农药对生态环境的危害及农药残留引发的食品安全等焦点问题出发，将具有独特菲环结构的松香骨架引入到噻吩杂环上，并通过活性亚结构拼接原理，接入噻二唑、酰胺、酰基硫脲、肟酯、schiff碱等活性基团制备了5系列新型松香基噻吩杂环光活化杀虫剂；在对小菜蛾和粘虫进行光活化杀虫作用评价的基础上，筛选出松香基噻吩具噻二唑酰胺结构系列化合物对粘虫幼虫呈现出较好的光活化杀虫效果，其中含有硝基取代基的化合物7e在光照处理24后，表现出最优的杀虫活性（LC50 = 0.613 μg/mL），与阳性对照α-三联噻吩接近（LC50 = 0.609 μg/mL）；在光活化活性筛选的基础上，结合症状学、分子毒理学和电子自旋共振等手段研究了化合物7e对粘虫幼虫生理生化的影响，并结合理论计算化学方法对其光诱导氧化作用的机理进行了初步探索，结果表明：光照使松香基噻吩骨架分子形成激发态，而噻二唑杂环基团的引入增强了松香基噻吩骨架分子的诱导和共轭效应，加快了电子从化合物到靶标的电子转移速率，使三线态氧更快的被激发形成高能量的单线态氧，并与粘虫的靶标进行反应引起氧化损伤，从而提高了该类化合物的杀虫效果；通过密度泛函理论研究，筛选出影响药剂分子光活化杀虫活性的4个关键分子结构描述符，并研究了药剂分子的手性中心、空间效应、电荷分布和能量变化等调控靶标位点的光动力学反应，建立了松香基噻吩杂环分子对应光活化杀虫活性的定量构效关系模型，从分子、电子的结构水平进一步揭示了药剂和受体的结合方式及作用机制。通过上述研究，可为新型高效松香基光活化杀虫剂的设计合成提供理论指导，并为松香在生物农药领域的高值化利用奠定基础。