The role of lipid fluidity in the interaction of DDT and some analogs with synthetic membranes

Abstract

The incorporation of two active chlorinated hydrocarbon insecticides (DDT and MeOC) and inactive DDE into vesicles of DPPC, DMPC, DOPC, and egg PC was studied by discontinuous sucrose gradient centrifugation. The extent of incorporation was used in the calculation of their partition coefficients and solubility in phospholipids. A fluid bilayer was essential for high incorporation. The partition coefficients and membrane saturation capacities were higher in fluid than in rigid membranes. Depending on the chemical, the lipid/aqueous partition coefficients were one to three orders of magnitude lower than the octanol/water partition coefficient. No significant difference was noted in these parameters for the three chemicals even though their hydrophobicities, as judged by their water solubilities, differed by about two orders of magnitude, suggesting that hydrophobicity does not ensure high lipophilicity. Furthermore the lack of correlation between these parameters and insecticidal activity indicates that the biological activities of these insecticides is not the result of specific interactions with the membrane lipids per se. A comparison of literature data with respect to the relative fluidity of various insect and mammalian membranes shows that insect membranes are strikingly more fluid. This would favor greater accumulation of chlorinated hydrocarbons into the unsaturated membranes as the first step in their action on a membrane-associated target site(s), and perhaps would partially explain their generally higher toxicity to insects.