title: pH-independent fluorescent chemosensor for highly selective lithium ion sensing.
abstract: 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+, Ca2+, Mg2+), a selectivity of log kLi+,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+.
authors.affiliation: Department of Applied Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. citteda@educ.cc.keio.ac.jp
authors.forename: Daniel
authors.initials: D
authors.lastname: Citterio
authors.forename: Junichiro
authors.initials: J
authors.lastname: Takeda
authors.forename: Masaki
authors.initials: M
authors.lastname: Kosugi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hisamoto
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D001665:Binding Sites; D002412:Cations / Q000032:analysis; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008094:Lithium / Q000032:analysis / Q000097:blood*; D013050:Spectrometry, Fluorescence
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D008094:Lithium