pH-independent fluorescent chemosensor for highly selective lithium ion sensing

Since lithium salts are used as pharmaceutically active compounds against manic-depressive psychosis, there is a demand to monitor the lithium concentration in blood in the narrow range of 0.6-1.2 mM effectively and safely. Here we report on an optical sensor approach for the determination of Li ⁺, based on the design and synthesis of a novel lithium fluoroionophore KLI-1 and its polymer immobilizable derivative KLI-2, and the application to an optode. The novel lithium fluoroionophores rely on a tetramethyl "blocking subunit" bearing 14-crown-4 as a Li ⁺-selective binding site and 4-methylcoumarin as a fluorophore, intramolecularly connected to show ICT-type wavelength shift for ratiometric fluorescence measurements. The fluoroionophores showed high selectivity for Li⁺ with binding-induced blue shift in the fluorescence spectra, no response to major biological interfering cations (K⁺, Ca ²⁺, Mg²⁺), a selectivity of log k_Li+,Na+ = -2.4 over Na⁺ in solution, and no response to pH in the range of pH 3-10. A hydrophilic optode membrane with KLI-2 immobilized also showed good selectivity for Li⁺, pH independence in the physiological range (pH 6-8), and fully reversible signal changes. KLI-1 and KLI-2 are excellent Li ⁺ fluorescent chemosensors that can be applied to quantitative measurements of lithium in clinical samples, although possible interference from Na⁺ has to be considered at the lower therapeutic level of Li ⁺.