PESTICIDES AND ION TRANSPORT ACROSS LIPID MEMBRANES

本项目是对渗透毒性形式的深入研究， 农药与脂膜相互作用，引起渗透性的变化， 质子和脂溶性离子。 这两类杀虫剂， 将研究的是（a）衍生自取代酚的那些， 充当质子载体并破坏细胞中的能量转换过程， (b)由氯化苯氧基和苯甲酸衍生的那些，包括 它们的代谢产物，改变膜的离子选择性。 的 建立农药膜定量模型的主要目的 相互作用将需要在三个一般领域进行协调研究： 第一个领域将是农药吸附的多方面探索。 将确定中性和电离的 水相和膜之间的农药形式，脂质单层， 和代表不同膜区域的有机溶剂。 这些 对农药引起的变化的调查将作为研究的补充 在有机脂质/水界面上的电势分布， 研究每种形式的杀虫剂在脂质阵列中的定位，以及 农药吸附热力学参数的测定。 的 所采用的方法包括脂质体的微电泳， 表面电位的测量、压缩等温线的测定 和等压线的脂质单层，和观察的凝胶流体 在膜上的转变。(2)第二个领域将侧重于 中性分子和离子化分子之间形成的氢键复合物 酚基农药，其在膜中的存在对于 农药介导的质子渗透性。 研究将包括 络合物在膜状溶剂中的稳定常数， 用各种方法制备的纯配合物的结构测定 有机抗衡离子 (3)第三个方面包括说明， 通过稳态和动态膜电导率测量 在动力学的时域和/或频域中操作， 杀虫剂改变了离子渗透性 动力学研究 质子泳农药将依赖于农药诱导的存在 膜电导率，而那些作为离子选择性的研究 改性剂将利用由膜建立的明确的传输方案， 离子探针 上述三个研究领域的成果结合 将为全面了解这些机制提供基础， 许多重要的杀虫剂干扰了 生物膜作为带电溶质的渗透屏障。

This project is an in depth study of the forms of permeatoxicity in which pesticides interact with lipid membranes causing changes of permeability to protons, and to lipid soluble ions. The two classes of pesticides which will be investigated are (a) those derived from substituted phenols, which act as protonophores and disrupt energy conversion processes in cells, and (b) those derived from chlorinated phenoxy and benzoic acids, including their metabolic products, which change ionic selectivity of membranes. The major goal of establishing quantitative models of pesticide-membrane interactions will require coordinated studies in three general areas: (1) The first area will be a multifaceted exploration of pesticide adsorption. Determinations will be made of the distribution of both neutral and ionized forms of pesticides between aqueous phases and membranes, lipid monolayers, and organic solvents representative of different membrane regions. These studies will be complemented by investigations of pesticide induced changes of electric potential profiles across organized-lipid/water interfaces, studies of where each form of pesticide is localized in lipid arrays, and measurements of the thermodynamic parameters of pesticide adsorption. The methods employed will include microelectrophoresis of liposomes, measurements of surface potential, determinations of compression isotherms and isobars of lipid monolayers, and observations of gel-fluid transformations in membranes. (2) The second area will focus on the hydrogen-bonded complexes formed between the neutral and ionized molecules of phenol-based pesticides whose presence in membrane is essential for pesticide-mediated proton permeability. Studies will include mesurements of stability constants of complexes in membrane-like solvents and structural determinations on complexes prepared in pure form with various organic counterions. (3) The third area encompasses the elucidation, through steady-state and dynamical membrane conductivity measurements operating in the time and/or frequency domains of the kinetics of pesticide-altered ionic permeability. The kinetic studies of protonophoretic pesticides will rely on the existence of pesticide-induced membrane conductivity, whereas studies of those acting as ion selectivity modifiers will utilize well defined transport schemes set up by membrane ion probes. The combination of results from the above three research areas will provide a basis for a comprehensive understanding of the mechanisms by which many important pesticides interfere with the crucial role of biomembranes as a permeability barrier to charged solutes.