EFFECT OF PHENYLTIN COMPOUNDS ON LIPID BILAYER ORGANIZATION

Phenyltin compounds are known to be biologically active. Their chemica l structure suggests that they are likely to interact with the lipid f raction of cell membranes, Using fluorescence and NMR techniques, the effect of phenyltin compounds on selected regions of model lipid bilay ers formed from phosphatidylcholine was studied. The polarization of N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl) dipalmitoyl-L-phosphatidylethanol amine and desorption of praseodymium ions was used to probe the polar region, whereas the polarization of 1 - (4 - trimethylammoniumphenyl) - 6-phenyl - 1,3,5-hexatriene p-toluenesulfonate measured the hydropho bic core of the membrane. In addition, changes in the N-(5-fluorescein thiocarbanoly)dipalmitoy - L - alpha - phosphatidylethanolamine fluore scence intensity indicated the amount of charge introduced by organoti n compounds to the membrane surface. There were no relevant changes of measured parameters when tetraphenyltin was introduced to the vesicle suspension. Diphenyltin chloride causes changes of the hydrophobic re gion, whereas the triphenyltin chloride seems to adsorb in the headgro up region of the lipid bilayer. When the hemolytic activity of phenylt in compounds was measured, triphenyltin chloride was the most effectiv e whereas diphenyltin chloride was much less effective. Tetraphenyltin causes little damage. Based on the presented data, a correlation betw een activity of those compounds to hemolysis (and toxicity) and the lo cation of the compound within the lipid bilayer could be proposed. In order to inflict damage on the plasma membrane, the compound has to pe netrate the lipid bilayer. Tetraphenylitin does not partition into the lipid fraction; therefore its destructive effect is negligible. The p artition of the compound into the lipid phase is not sufficient enough , by itself, to change the structure of the lipid bilayer to a biologi cally relevant degree. The hemolytic potency seems to be dependent on the location of the compound within the lipid bilayer. Triphenyltin ch loride which adsorbs on the surface of the membrane, causes a high lev el of hemolysis, whereas diphenyltin chloride, which penetrates much d eeper, seems to have only limited potency. (C) 1998 John Whey & Sons, Ltd.