LIPOPHILIC LI+ ION FLUOROPHORES

IT IS PLANNED TO SYNTHESIZE A NEW FAMILY OF LIPOPHILIC LI(+)ION FLUOROPHORES THAT MAY ULTIMATELY FIND USE IN A VARIETY OF APPLICATIONS OF INTEREST TO CELL PHYSIOLOGISTS AND NEUROSCIENTISTS. THESE FLUOROPHORES WILL BE ABLE TO FUNCTION IN CELL MEMBRANES AS LITHIUM ION CARRIERS TO TRANSPORT LI(+) INTO THE CYTOPLASM FOR STUDY OF THE INHIBITION OF INOSITOL PHOSPHATE METABOLISM. WITH SOME ALTERATIONS OF SUBSTITUENT GROUPS, THEY MAY BE USED TO DETERMINE THE CONCENTRATION OF CYTOSOLIC LITHIUM ION AND/OR FOR DIRECT OBSERVATION OF TEMPORAL AND SPATIAL CHANGES IN LI(+) ION CONCENTRATIONS IN SINGLE CELLS. THEY MAY ALSO BE USED IN VITRO TO DETERMINE LITHIUM IN THE BLOOD SERUM OF PATIENTS BEING TREATED FOR MANIC-DEPRESSIVE PSYCHOSIS. IN PHASE I, COVALENT ASSOCIATES, INC., WILL SYNTHESIZE THE SIMPLEST MEMBER OF THIS GROUP OF FLUOROPHORES TO TEST THE PROPOSED SYNTHESIS ROUTE AND TO DETERMINE WHETHER IT WILL FUNCTION IN VITRO AS A SELECTIVE FLUOROPHORE FOR LI(+) ION. IN PHASE II, OTHER ANALOGS WILL BE SYNTHESIZED WITH FLUOROPHORES HAVING LONG WAVELENGTH EMISSIONS AND GREATER HYDROPHOBICITY. THEIR POSSIBLE USE FOR THE IN VITRO DETERMINATION OF LI(+) IN BLOOD SERUM AND FOR THE DETERMINATION OF CYTOSOLIC FREE LI(+) ION CONCENTRATION IN VIABLE CELLS WILL ALSO BE EXPLORED.