Effects of insecticide acephate on membrane mimetic systems: The role played by electrostatic interactions with lipid polar headgroups

Abstract Pesticides are important agrochemicals to yield high crop productivity but their indiscriminate use may harm the environment and human health. In order to seek a compromise between effectiveness as insecticide and safety for humans, it is essential to correlate their physiological action with molecular-level interaction with cell membranes. In this study, we found that acephate interacts preferentially with positively charged Langmuir monolayers that represent simplified cell membranes. This was proven by comparing surface pressure-molecular area (π-A) isotherms and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) data on monolayers of the zwitterionic 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), the cationic dimethyldioctadecyl ammonium bromide (DODAB) and 1,2-dipalmitoyl-3-trimethylammonium-propane (DPTAP), and the anionic dihexadecyl phosphate (DHP) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA). While acephate induced a closer packing of DODAB and DPTAP monolayers upon binding to their quaternary ammonium and choline groups, respectively, almost no effects were observed in the π-A isotherms of the other lipids. Such preferred interaction between acephate and the positively-charged groups was confirmed with density-functional theory (DFT) calculations. Acephate also changed the size and zeta potential of large unilamellar vesicles (LUVs) formed with cationic lipids. Taken together these results point to a physiological action related to acephate binding to positively charged groups owing to its negative character, which may help establish conditions for the safe use of this insecticide.