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+.

A Fast-Response pH Optode Based on a Fluoroionophore Immobilized to a Mesoporous Silica Thin Film

“…The response times of the sensor in a continuous sample flow mode were recorded by placing a mesoporous silica thin-film coated round-shaped glass disc in a small-volume flow cell constructed in our laboratory. 16 Samples were delivered to the flow cell in a constant flow of 1 mL/min using a peristaltic pump SJ-1211H (ATTO Corp., Tokyo, Japan) system. Figure 1 shows the synthesis scheme for the preparation of the pH optode.…”

The role of the size of aza-crown recognition moiety in azaphthalocyanine fluorescence sensors for alkali and alkaline earth metal cations

“…Due to their high sensitivity, ultra-fast response, and the compatibility of instrumentation with the biological environment, the fluorescence sensing devices are gaining increased attention for the analysis of metal ions over other methods. Metal cation recognition is very important for quantification of blood electrolytes [2], cations involved in ion-channel transportation [3], or for monitoring of lithium [4] and potassium [2] levels in the treatment of bipolar disorder and hypertension, respectively.…”

On the merits of tetrapolar impedance spectroscopy for monitoring lithium concentration variations in human blood plasma

“…Spectrofluorimetric techniques [31,32] rely upon the reaction of lithium to a specific fluoroionophore however, to the authors' knowledge; their functionality using blood samples has not been demonstrated yet. Spectrophotometric techniques [33] make use of specific dyes which react with lithium causing a shift in light absorbance wavelengths.…”