Design and synthesis of a more highly selective ammonium ionophore than nonactin and its application as an ion-sensing component for an ion-selective electrode

A novel ammonium ionophore, which exhibits superior NH4+ selectivity compared with that of the natural antibiotic nonactin, was successfully designed and synthesized based on a 19-membered crown compound (TD19C6) having three decalino subunits in the macrocyclic system. This bulky decalino subunit is effective for (1) increasing the structural rigidity of the cyclic compound, (2) introducing the "block-wall effect", which prevents forming a complex with a large ion, and (3) increasing the lipophilicity of the ionophore molecule. In the ammonium ionophore design, the first factor contributes to increasing the NH4+ selectivity relative to smaller ions such as Li+, Na+, or even the closest size, K+, and the second factor increases the NH4+ selectivity over larger ions such as Rb+ and Cs+. The X-ray structural analysis proved that TD19C6 forms a size-fit complexwith NH4+ in its crown ring cavity. As an application of this ionophore, an ion sensor (ion-selective electrode) was prepared, which exhibited NH4+ to K+ and Na+ selectivity of 10 and 3,000 times, respectively. This electrode showed a better performance compared to the electrode based on nonactin, which is the only ammonium ionophore presently used in practical applications.

Integrated multilayer flow system on a microchip.

We utilized microchip technology and found that the multilayer flow of liquids can be formed in microchannels. Liquid/liquid interfaces were formed parallel to the side wall of the microchannels, because the surface tension and friction force are stronger than the force of gravity. A water/ethylacetate/water interface was formed in a 70-microm-wide and 30-microm-deep channel. The interface was observed to be quite stable and to be maintained for a distance of more than 18 cm. As an example of a multilayer flow application, we demonstrated the liquid/liquid extraction of Co-dimethylaminophenol complex in a microchannel. The solvent-extraction process of the complex into m-xylene in the multilayer flow was found to reach equilibrium in 4 s, while it took 60 s in a simple two-phase extraction.

Visual and colorimetric lithium ion sensing based on digital color analysis.

A new optical analytical method, "Digital Color Analysis (DCA)", is proposed based on a digital color analyzer instead of the conventional optical methodology, "Spectrophotometry". The digital color analyzer is a hand-held-size instrument for measuring "colors", and it can transform the color information into numerical values, color library data, etc., that can be treated as analytical information. DCA gives us a more informative analytical method than spectrophotometry by treating colors as digital information. In addition, DCA can also simulate the optimum color variations for optimization of the visual sensor with computer assistance. By utilizing colors as digital information, colorimetric analysis that has been used for only semiquantitative analysis can serve as an accurate determination method. On the basis of DCA, we developed a plasticized PVC film optode and a paper optode for Li+ determination in saliva. After the optimization of color variation and the detection range for the Li+ measurements, the optode membrane gives colorless gray in the Li+ therapeutic range (at 10(-3) M) in saliva. Consequently, whether or not the optimum therapeutic Li+ concentration is maintained can be easily evaluated with these optodes. Especially, the sensing paper optode can be easily handled within a short measurement time (approximately 80 s) which is suitable for home use. Using the digital color analyzer with QxQy coordinates, a linear relation calibration curve can be obtained over the range from 10(-5) to 10(-1) M Li+, in which the analyzer can detect a concentration difference of approximately 0.1 mM Li+. For the near future, an accurate and simple analysis is needed for a health check at home that does not require going to a hospital. The optode based on DCA has great potential for this analytical purpose.

On-chip integration of sequential ion-sensing system based on intermittent reagent pumping and formation of two-layer flow.

A sequential ion-sensing system using a single microchip was successfully realized. The system developed here involves intermittent pumping of plural organic phases into a microchannel, followed by contact with a single aqueous phase to form a stable organic-aqueous two-layer flow inside the microchannel. Because the plural organic phases created by intermittent flow contain the same lipophilic pH indicator dye but different ion-selective neutral ionophores, different ions can be sequentially and selectively extracted into the different organic phases, where they can be determined by thermal lens microscopy (TLM). We used KD-A3 as the lipophilic pH indicator dye and valinomycin and DD16C5 as neutral ionophores to demonstrate sequential ion sensing of potassium and sodium ions by measuring the deprotonated dye caused by the ion extraction. The integrated microfluidic system proposed here allows multi-ion sensing, which is not easily demonstrated by conventional ion sensor technology using a solvent polymeric membrane. The minimum volume of single organic phase needed to obtain an equilibrium response without dilution by cross dispersion of two organic phases was ca. 500 nL in our system, indicating that the required amounts of expensive reagents in one measurement could be reduced to 1.7 ng and 2.8 ng for the dye and ionophore molecules, respectively.

Theory and Practice of Rapid Flow-Through Analysis Based on Optode Detection and Its Application to pH Measurement as a Model Case.

Rapid flow-through analysis (RFA) based on optode (optical chemical sensor) detection is proposed, and its performance is discussed using the RFA system equipped with a pH-sensitive optode as a model case. To demonstrate and understand the usefulness of the RFA system, long-lifetime pH-sensitive optodes were prepared using a hydrophilic poly(hydroxyethyl methacrylate) (poly-HEMA) membrane covalently immobilized with a dye containing an amino group such as Congo Red or Nile Blue. The response equation for the optode with the RFA system was proposed, and satisfactory estimation for rapid pH analysis was obtained. The proposed RFA can stand as an advanced method for conventional flow injection analysis.

Optical determination of low-level water concentrations in organic solvents using fluorescent acridinyl dyes and dye-immobilized polymer membranes.

The fluorescent acridinyl indicators 4-(9-acridinyl)-N-(5-hexenyl)-N-methylaniline (KD-F0011), 6-(9-acridinyl)-1,2,2,3-tetramethyl-2,3-dihydro- 1H-perimidine (KD-F0021), and 6-(9-acridinyl)-2-(3-butenyl)-1,2,3-trimethyl-2,3-dihydro-1H-perimidine (KD-F0022) were designed, synthesized, and applied for highly sensitive optical determination of low-level water in organic solvents. All these dyes were found useful as fluorescence indicators for the detection of water below 1% (v/v) in different solvent media with a low detection limit of 0.002% (v/v) or 20 mg/L (22 ppm by weight) for KD-F0021 in THF solution. Sensing membranes made from poly(ethylene glycol) dimethacrylate by photocopolymerization with the indicator KD-F0011 were also prepared. Using the membrane sensor, the lowest detection limit of 0.001% (v/v) or 14 mg/L (20 ppm) water was achieved in diethyl ether samples. This system enables the continuous monitoring of the water content in a flow-through arrangement, where single-wavelength excitation (404 nm) and single-wavelength detection (532 mm) can be used for the fluorescence determination, allowing a simple measurement setup. In a continuous-flow experiment using THF samples, fully reversible and fast signal changes with t95% = 1-2 min for water concentrations up to 0.50% (v/v) were observed. A detection limit of 0.004% (v/v) or 40 mg/L (45 ppm) water in THF was achieved. These characteristics make this type of sensor a useful tool for the online continuous monitoring of water present as an impurity in organic media, which is difficult to achieve using a Karl Fischer instrument.

Molecular Design, Characterization, and Application of Multiinformation Dyes for Multidimensional Optical Chemical Sensings. 2. Preparation of the Optical Sensing Membranes for the Simultaneous Measurements of pH and Water Content in Organic Media.

Optical chemical sensing of pH and water content in organic solvents is proposed, using multiinformation dyes (MIDs) based on the support matrixes for the dyes. In this investigation, four kinds of merocyanine-type dyes having a polymerizable olefin unit as the MIDs were synthesized. These dyes were copolymerized with hydrophilic monomer molecules to obtain dye-immobilized optical chemical sensor (optode) membranes. In this case, selection of the monomer molecule gave optode membranes having different color change properties, because different monomer molecules provided different chemical environments around the immobilized dye. These optode membranes were used for the measurement of pH and water content in organic solvents. These membranes offered two-dimensional sensing information in one spectrum when they were employed for water content sensing in organic solvents, in which the maximum wavelength represents the water content and the absorbance at this wavelength represents the pH of the water present. These polymer membranes have a long lifetime, which can be adequate for practical use.

Molecular Design, Characterization, and Application of Multiinformation Dyes (MIDs) for Optical Chemical Sensings. 3. Application of MIDs for λ(max)-Tunable Ion-Selective Optodes.

By utilizing "multiinformation dyes (MIDs)", which have plural spectral change characteristics such as an absorption maximum wavelength (λ(max)) shift based on a polarity change and an absorbance change due to protonation, novel λ(max)-tunable ion-selective optodes were proposed and prepared by employing MIDs with membrane solvents having different polarities. For controlling the detecting λ(max) of the optode, the novel polar membrane solvent [2-[[6-(2-nitrophenoxy)hexyl]oxy]methyl]isobutane-1,3-diol was designed and synthesized, which was used together with a typical membrane solvent nitrophenyl octyl ether. By mixing these two membrane solvents, the λ(max) position of the optode detection wavelength can be shifted and controlled and was successfully applied to a λ(max)-tunable Li(+)-selective optode based on a highly Li(+)-selective ionophore TTD14C4. The λ(max) tuning technique is useful for preparing an optode system using a low-cost light source such as a light-emitting diode or a popular laser.

Design and synthesis of sodium ion-selective ionophores based on 16-crown-5 derivatives for an ion-selective electrode.

To develop an ionophore that is highly selective for sodium for use in an ion-selective electrode, we propose a model based on 16-crown-5 which has a cavity just the size of Na(+ )and has a "block" subunit to prevent complex formation with ions larger than Na(+). Based on this molecular model, eight kinds of 16-crown-5 derivatives have been synthesized, and their structural ion selectivity has been evaluated in detail. The 16-crown-5 derivatives having two bulky "block" subunits showed high Na(+) selectivity relative to K(+). In particular, the derivative with two decalino subunits (DD16C5) exhibited the highest Na(+) selectivity of all the ionophores examined. When a phosphate ester-type membrane plasticizer, tris(ethylhexyl) phosphate, was used as the membrane solvent for the ion-sensing membrane based on poly(vinyl chloride), the electrode using DD16C5 exhibited a Na(+) selectivity of over 1000 times relative to alkali metal and alkaline earth metal ions, including K(+), which is the most serious interferant. The evaluation of the relationship between the ionophore chemical structures and the ion-selective features contributes to the host-guest chemistry to give a highly selective ionophore for an alkali metal ion.

Structural ion selectivity of thia crown ether compounds with a bulky block subunit and their application as an ion-sensing component for an ion-selective electrode.

Several 14-membered thia crown ether ionophores having a bulky block subunit were synthesized, and their chemical structures and ion selectivities were examined in detail when these compounds were used as an ion-sensing component of an ion-selective electrode. The ionophores of both cyclic and noncyclic thia ethers exhibited a high selectivity for silver ion (Ag(+)), in which the sulfur atom in the ionophore molecule plays a role as the effective coordination donor site for the silver ion. The best Ag(+)-selective electrode was prepared with the 14-membered thia crown ether having one sulfur atom, three oxygen atoms, and a bulky pinan subunit. The ion selectivity of this electrode for Ag(+) was over 10(4) times that for other metal cations. In the case where the sulfide in the thia ether ionophore was changed to sulfoxide by oxidation, ion selectivity for mercury ion became higher; therefore, the sulfoxide was found to be an effective coordination site for the mercury ion. The ion selectivity features of noncyclic sulfide, sulfoxide, and sulfone were also examined and compared with the results of the cyclic and noncyclic thia ethers.