SEMIFLUORINATED SYMMETRICAL DIETHERS FOR INTRAOCULAR USE: SYNTHESIS, CHARACTERIZATION, AND IN VITRO BIOCOMPATIBILITY

Abstract

Semifluorinated symmetrical diethers were synthesized using the William ether synthesis. These diethers should have similar properties to perfluorocarbons as are chemical inertness and high oxygen solubility, but in contrast a considerably lower density. With their lower density the damaging of the choroidal tissue of the eye observed with perfluorocarbons should be avoided. The synthesized diethers are inert compounds being stable against nucleophiles, oxidiziers and strong bases. Their density is in the range of 1.1–1.2 g/cm³. Besides the physical and chemical tests we conducted several in vitro biocompatibility tests. The tests comprised induction of hemolysis, the generation of C3a complement, the influence on the production of interleukin1β, the influence on cell proliferation of a Raji and a Hela cell line (³H-Thymidine uptake) and finally the direct cytotoxic effect on these cell lines. All tested symmetrical diethers were positive in one or more tests and can be expected to be incompatible in vivo. Especially the “short” semifluorinated diethers [(CF₃CH₂O)₂(CH₂)_3–6] showed a nearly total inhibition of cell proliferation or interleukin1β release. Further variation of the compounds will be necessary to generate better biocompatible derivates.