Synthesis and preliminary data on the biocompatibility and emulsifying properties of perfluoroalkylated phosphoramidates as injectable surfactants

Article abstract of DOI:10.1016/0223-5234(91)90151-C

Perfluoroalkylated dimorpholinophosphoramidates, 1-4, were synthesized in 65-80% yield by phosphorylation of the appropriate perfluoroalkylated alcohol by phosphorus oxytrichloride, followed by reaction with morpholine. Preliminary biological tests (effect on cell cultures, hemolysis of red blood cells, and acute in vivo toxicity in mice) performed on compounds 1 to 5 show that the F-alkylated derivatives 1 to 4 are better tolerated than their hydrocarbon analog 5 in spite of their higher surface activity. Where the emulsification of fluorocarbons is concerned, the incorporation of the perfluoroalkylated compounds 1 to 4 in 20% w/v F-decalin/lecithin-based emulsions results in a slight stabilizing effect (not found for the hydrocarbon analog 5), detectable only after one month of storage at 25°C. However, when used as the sole surfactant, the F-alkylated dimorpholinophosphoramidates show no emulsifying properties; this may be assigned to insufficient hydrophilicity of the dimorpholinophosphoramidate head.