NEW PERFLUOROALKYLATED AMPHIPHILES CONTAINING POLY(ETHYLENE GLYCOL)-PHOSPHATE ESTER HEAD GROUPS - SYNTHESIS, SURFACE-ACTIVITY, FLUOROCARBONEMULSIFYING CAPABILITY AND BIOLOGICAL PROPERTIES

A series of new perfluoroalkylated phosphate triesters 1 to 4 and anio nic phosphate diesters 5 of various methoxypolyethylene glycols have b een synthetized. Compounds 1 to 4 have been obtained in 50-55% yields by phosphorylation of the F-alkylated alcohol using phosphorus oxytric hloride followed by condensation with the corresponding polyethylene g lycol monomethyl ether. Compound 5 was obtained in 28% overall yield u sing the H-phosphonate method. Compound 1 is neither soluble nor dispe rsible in water, but compounds 2 to 5 all exhibit high surface activit y; the most efficient and most effective is 3. The anionic diester 5 e xhibits the most efficient F-decalin (FDC) emulsifying properties of a ll the esters 2 to 5. However, 5 is less efficient as a sole surfactan t than natural egg yolk phospholipids (EYP) or Pluronic F-68. The use of 2, 4 or 5 in conjunction with EYP for the preparation of 50% w/v FD C emulsions resulted in a higher average particle size than that found in the emulsions prepared with EYP alone. The use of F-alkylated deri vatives 4 and 5 as co-surfactants with EYP induces a comparable low (b ut significant) destabilizing effect on the emulsion shelf stability. Compound 2 induces a significantly greater destabilizing effect compar ed with 4 and 5. Nevertheless, all the emulsions formulated with EYP a nd these F-alkylated derivatives are still more stable (at least 5 tim es) than any emulsion formulated with Pluronic F-68. When used as co-s urfactants of Pluronic F-68, compounds 2 and 4 have no significant eff ect on particle size or emulsion stability. A low but significant dest abilizing effect was found for compound 5 as a co-surfactant with Plur onic F-68. The new F-alkylated surfactants 2 to 5 show no detectable h emolytic activity even at concentrations as high as 25 g/L. Most impor tantly, it is found that compounds 4 and 5 have maximal tolerated dose s (MTD) higher than 2 g/kg when administered intravenously in mice and thus display a very promising in vivo tolerance. Compounds 4 and 5 ar e among the few perfluoroalkylated surfactants reported so far that ha ve been found to exhibit such high MTD values.