We propose to synthesize a new family of lipophilic Li+ ion fluorophores which may ultimately find use in a variety of applications of interest to cell physiologists and neuroscientists. They 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 useful to determine the concentration of cytosolic lithium ion and/or for direct observation of temporal and spacial 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. Immobilization of the fluorophore on the end of a fiber optic sensor could eventually lead to in vivo determination of Li+ in blood. In Phase I, we intend to synthesize the simplest member of this group of fluorophores to test the synthesis route we have proposed, and to determine whether it will function in vitro as a selective fluorophore for Li+ ion. In Phase II we will synthesize other analogs with fluorophores having long wavelength emissions and greater hydrophobicity. We will also explore their possible use for the in vitro determination of Li+ in blood serum, and for determination of cytosolic free Li+ ion concentration in viable cells.
