論文

To investigate the π-extension effect on an unusual negative-charged spin crossover (SCO) FeIII complex with a weak N2O4 first coordination sphere, we designed and synthesized a series of anionic FeIII complexes from a π-extended naphthalene derivative ligand. Acetonitrile-solvate tetramethylammonium (TMA) salt 1 exhibited an SCO conversion, while acetone-solvate TMA salt 2 was in a high-spin state. The crystal structural analysis for 2 revealed that two-leg ladder-like cation-anion arrays derived from π-stacking interactions between π-ligands of the FeIII complex anion and Coulomb interactions were found and the solvated acetone molecules were in one-dimensional channels between the cation-anion arrays. A desolvation-induced single-crystal-to-single-crystal transformation to desolvate compound 2’ may be driven by Coulomb energy gain. Furthermore, the structural comparison between quasi-polymorphic compounds 1 and 2 revealed that the synergy between Coulomb and π-stacking interactions induces a significant distortion of coordination structure of 2.

Cadmium sulphide (CdS) nanoparticles were chemically synthesized using reverse micelles microreactor methods. By using different washing treatments, UV-Vis spectroscopy showed that the absorption peaks appeared at 465 nm, 462 nm, 460 nm, and 459 nm respectively for CdS nanoparticles without and with 1, 2, and 3 times washing treatments using pure water. In comparison with the absorbance peak of bulk CdS at 512 nm, the shifted absorption peaks, indicates that the different sizes of CdS can be prepared. Anodic stripping voltammetry of the CdS nanoparticles was then studied at a boron-doped diamond electrode using 0.1 M KClO4 and 0.1 M HClO4 as the electrolytes. A scan rate of 100 mV/s with a deposition potential of-1000 mV (vs. Ag/AgCl) for 60 s at a potential scan from-1600 mV to +800 mV (vs. Ag/AgCl) was applied as the optimum condition of the measurements. Highly-accurate linear calibration curves (R2 = 0.99) in 0.1 M HClO4 with the sensitivity of 0.075 mA/mM and the limit of detection of 81 μM in 0.1 M HClO4 can be achieved, which is promising for an application of CdS nanoparticles as a label for biosensors.

Electroreduction of CO2 was studied at copper-modified boron-doped diamond (Cu-BDD) electrodes as the working electrode. The Cu-BDD electrodes were prepared by electrochemical reduction with various concentrations of CuSO4 solutions. FE-SEM was utilized to characterize the electrodes. At Cu-BDD electrodes, a reduction peak at around-1.2 V (vs Ag/AgCl) attributtable to CO2 reductions could be observed by cyclic voltammetry technique of CO2 bubbled in water containing 0.1M NaCl. Accordingly, electroreduction of CO2 was conducted at-1.2 V (vs Ag/AgCl) using amperometry technique. The chemical products of the electroreduction analyzed by using HPLC showed the formation of formaldehyde, formic acid, and acetic acid at Cu-BDD electrodes.

Biomolecule modified magnetic beads has been widely used in separation and sensing process. This study used streptavidin modified magnetic beads to immobilize biotin modified zanamivir. Biotin-streptavidin affinity facilitates immobilization of zanamivir on magnetic beads. Then interaction of zanamivir and neuraminidase was adopted as basic for enzyme detection. Detection of neuraminidase was performed at gold modified BDD using cyclic voltammetry technique. The measurement was carried out based on alteration of electrochemical signals of working electrode as neuraminidase response. The result showed that zanamivir was successfully immobilized on magnetic beads. The optimum amount of magnetic beads for zanamivir immobilization was 120 ug. Linear responses of neuraminidase were detected in concentration range of 0-15 mU. Detection limit (LOD) of measurement was 2.32 mU (R2 = 0.959) with precision as % RSD of 1.41%. Measurement of neuraminidase on magnetic beads could be also performed in the presence of mucin matrix. The linearity range was 0-8 mU with LOD of 0.64 mU (R2 = 0.950) and % RSD of 7.25%.

Boron-doped diamond (BDD) microelectrodes were used to observe the correlation between electrocatalytic currents caused by individual Pt nanoparticle (Pt-np) collisions at the electrode. The BDD microelectrodes, ∼20 μm diameter and ∼2 μm particle size, were fabricated at the surface of tungsten wires. Pt-np with a size of 1 to 5 nm with agglomerations up to 20 nm was used for observation. The electrolytic currents were observed via catalytic reaction of 15 mM hydrazine in 50 mM phosphate buffer solution at Pt-np at 0.4 V when it collides with the surface of the microelectrodes. The low current noise and wider potential window in the measurements using BDD microelectrode produced a better results, which represents a better correlation to the TEM result of the Pt-np, compared to when gold microelectrodes was used.

Background: Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine–glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. Methods: SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Results: Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. Conclusions: This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

Gold nanoparticles-modified boron-doped diamond (AuNPs-BDD) electrodes, which were prepared with a self-assembly deposition of AuNPs at amine-terminated boron-doped diamond, were examined for voltammetric detection of neuraminidase (NA). The detection method was performed based on the difference of electrochemical responses of zanamivir at gold surface before and after the reaction with NA in phosphate buffer solution (PBS, pH 5.5). A linear calibration curve for zanamivir in 0.1 M PBS in the absence of NA was achieved in the concentration range of 1 × 10-6 to 1 × 10-5 M (R2 = 0.99) with an estimated limit of detection (LOD) of 2.29 × 10-6 M. Furthermore, using its reaction with 1.00 × 10-5 M zanamivir, a linear calibration curve of NA can be obtained in the concentration range of 0-12 mU (R2 = 0.99) with an estimated LOD of 0.12 mU. High reproducibility was shown with a relative standard deviation (RSD) of 1.14% (n = 30). These performances could be maintained when the detection was performed in mucin matrix. Comparison performed using gold-modified BDD (Au-BDD) electrodes suggested that the good performance of the detection method is due to the stability of the gold particles position at the BDD surface.

Unprecedented anionic FeIII spin crossover (SCO) complexes involving a weak-field O,N,O-tridentate ligand were discovered. The SCO transition was evidenced by the temperature variations in magnetic susceptibility, Mössbauer spectrum, and coordination structure. The DFT calculations suggested that larger coefficients on the azo group in the HOMO-1 of a ligand might contribute to the enhancement of a ligand-field splitting energy. The present anionic SCO complex also exhibited the light- induced excited-spin-state trapping effect. Photoinduced spin transition: Unprecedented anionic spin crossover (SCO) complexes involving a weak-field FeIIIN2O4 coordination sphere were discovered. The tetramethylammonium salt of the depicted SCO anion exhibited the light-induced excited-spin-state trapping effect, which is quite rare in FeIII SCO complexes (see scheme).

We have developed a lab-on-a-chip (LOC) platform for electrochemical detection and degradation of the pesticide atrazine (Atz). It is based on boron-doped diamond (BDD) electrodes and a competitive magneto-enzyme immunoassay (EIA) that enables high sensitivity. To detect the enzymatic reaction, we employed a BDD electrode modified with platinum nanoparticles (PtNPs), as a highly conductive catalytic transducer. Chronoamperometry revealed a limit of detection (LOD) of 3.5pM for atrazine, which, to the best of our knowledge, is one of the lowest value published to date. Finally, we degraded Atz in the same platform, using a bare BDD electrode that features remarkable corrosion stability, a wide potential window, and much higher O2 overvoltage as compared to conventional electrodes. These characteristics enable the electrode to produce a greater amount of HO• on the anode surface than do conventional electrodes and consequently, to destroy the pollutant more rapidly. Our new LOC platform might prove interesting as a smart system for detection and remediation of diverse pesticides and other contaminants.

Electrochemical oxidation of adenosine phosphates, including adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), and adenosine 5'-triphosphate (ATP), have been studied using boron-doped diamond (BDD) electrodes. Cyclic voltammograms in phosphate buffer solution pH7.4 showed a typical oxidation peak at the potential of around +1.3V (vs. Ag/AgCl) attributable to the oxidation of adenine base moiety. This peak appears at both cathodically and anodically treated BDD. However, investigation at low pH showed, whereas the oxidation peak could be well observed for the oxidation of each AMP, ADP, and ATP at cathodically treated BDD, it was only found for the oxidation of AMP at anodically-treted BDD electrodes. Linear calibration curve can be achieved in the concentration range of 20 to 200μM with an average detection limit of 2μM (S/N=3). Furthermore, cathodic treatment has demonstrated its ability to maintain the electrode surface from biofouling, resulting in the excellent stability of current responses.

Although oxidoreductases are widely used in many applications, such as biosensors and biofuel cells, improvements in the function of existing oxidoreductases or the discovery of novel oxidoreductases with greater activity is desired. To increase the activity of oxidoreductases by directed evolution, a powerful screening technique for oxidoreductases is required. In this study, we developed a microfluidic total analysis system for high-throughput screening of NAD(P)-dependent oxidoreductases. This system comprises three microfluidic devices: an encapsulating device, a NADH measuring device, and a magnetic beads sorting device. We demonstrated the utility of each part of the system.

A simple and reliable enzymatic system for organophosporus pesticide detection was successfully developed, by exploiting the synergy between the magnetic beads collection capacity and the outstanding electrochemistry property of boron-doped diamond electrodes. The determination of an organophosphate pesticide, chlorpyrifos (CPF), was performed based on the inhibition system of the enzyme acetylcholinesterase bonded to magnetic beads through a biotin-streptavidin complex system. A better sensitivity was found for a system with magnetic beads in the concentration range of 10-9 to 10-5 M. The estimated limits of detection based on IC10 (10% acetylcholinesterase (AChE) inhibition) have been detected and optimized to be 5.7 × 10-10 M CPF. Spiked samples of water of Yokohama (Japan) have been measured to validate the efficiency of the enzymatic system. The results suggested that the use of magnetic beads to immobilize biomolecules or biosensing agents is suitable to maintain the superiority of BDD electrodes.

A gold nanoparticle modified boron-doped diamond electrode was developed as a transducer for biochemical oxygen demand (BOD) measurements. Rhodotorula mucilaginosa UICC Y-181 was immobilized in a sodium alginate matrix, and used as a biosensing agent. Cyclic voltammetry was applied to study the oxygen reduction reaction at the electrode, while amperometry was employed to detect oxygen, which was not consumed by the microorganisms. The optimum waiting time of 25 min was observed using 1-mm thickness of yeast film. A comparison against the system with free yeast cells shows less sensitivity of the current responses with a linear dynamic range (R2 = 0.99) of from 0.10 mM to 0.90 mM glucose (equivalent to 10 - 90 mg/L BOD) with an estimated limit of detection of 1.90 mg/L BOD. However, a better stability of the current responses could be achieved with an RSD of 3.35%. Moreover, less influence from the presence of copper ions was observed. The results indicate that the yeast-immobilized BOD sensors is more suitable to be applied in a real condition.

The development of boron doped diamond (BDD) as electrode material lead to significant improvement toward optimal sensitivity, reproducibility and stability during the in vivo monitoring of electroactive species. The most recent developments in the field of biosensing using BDD electrodes, namely the fabrication of the sensor and application in monitoring of dopamine and glutathione, are described in this chapter.

A novel star-shaped high-spin Fe(III) tetranuclear cluster was unexpectedly obtained by the reaction of an [FeIII(phsal)2]- anion with an Fe(II) coordination cation (H2phsal: N-(2- hydroxyphenyl)salicylaldimine). Despite a star-shaped Fe(III) tetranuclear structure similar to reported Fe(III) single molecule magnets, the present compound exhibited a bulk antiferromagnetic transition at 0.6K due to a magnetic exchange coupling through intercluster π-stacking interactions.

A prototype microfluidic device using boron-doped diamond (BDD) electrodes patterned on an alumina chip was designed and fabricated. Electrochemical microfluidic devices have advantages in that the amount of sample required is small, the measurement throughput is high, different functions can be integrated on a single device, and they are highly durable. In using the device for the flow injection analysis of oxalic acid, the application of a brief conditioning step ensured that the reproducibility of the current signal was excellent.Furthermore, the fabricated system also performed as a prototype of "elimination-detection flow system", in which interfering species are eliminated using "elimination electrodes" prior to the species reaching the "detection electrode". The fabricated device reduced the current due to interfering species by 78%. Designs of devices to improve this efficiency are also discussed.

To introduce both an inter-sulphur atom and π-stacking interaction between a spin crossover (SCO) cation and paramagnetic anion, we designed and synthesised two novel Fe(ii) SCO compounds involving a terpyridine-type thiazole containing ligand with the paramagnetic Ni(dmit)2 and nonmagnetic Au(dmit)2 anion (dmit = 4,5-dithiolato-1,3-dithiole-2-thione). The temperature variations of magnetic susceptibility and Mössbauer spectroscopy revealed that both complexes exhibited an almost complete SCO conversion, and moreover, the Ni(dmit)2 anion was in a paramagnetic state down to 2 K. The crystal structures for the Ni(dmit)2 complex at 213 and 400 K indicated that the chalcogen-bond and π-stacking interaction would be enhanced by the electrostatic interaction between the cation and anion, preventing the π-radicals from dimerising. The light-induced excited spin state trapping effect was observed at 5 K.

This study emphasizes the electrochemical detection of Neuraminidase (NA) based on NA inhibition by Zanamivir. The detection method was developed based on the difference of electrochemical responses of Zanamivir in the presence and the absence of NA in phosphate buffer solution (pH 5.5). Gold and gold-modified boron-doped diamond was used as the working electrode and the measurement was conducted using cyclic voltammetry method. A linear calibration curve of Zanamivir was observed in the concentration range of 5 × 10-6-1 × 10-4 mol/L (R2 = 0.991), with the estimated limit of detection (LOD) of 1.49 × 10-6 mol/L. The presence of NA increases the peak current of gold oxidation and reduction with linear calibration curves were monitored in the concentration range of 0-15mU (R2 = 0.996). An estimated LOD of 0.25mU NA and an excellent reproducibility of the detection with an RSD of 1.18% can be achieved. Application of a real sample was successfully demonstrated for NA detection in the presence of mucin, suggested that the method is promising for pharmaceutical or medical application.

The whole molecule of the title compound, C22H28Br2O2, is generated by twofold rotation symmetry. The dihedral angle of the biphenyl moiety is 85.05 (11)°. The hydroxy groups show intramolecular O - H⋯π interactions without any other hydrogen-bond acceptors. In the crystal, there are no other significant intermolecular interactions present.

Anodic stripping voltammetry (ASV) of colloidal gold-nanoparticles (AuNPs) was investigated at boron-doped diamond (BDD) electrodes in 50 mM HClO4. A deposition time of 300 s at-0.2 V (vs. Ag/AgCl) was fixed as the condition for the ASV. The voltammograms showed oxidation peaks that could be attributed to the oxidation of gold. These oxidation peaks were then investigated for potential application in immunochromatographic strip tests for the selective and quantitative detection of melamine, in which AuNPs were used as the label for the antibody of melamine. Linear regression of the oxidation peak currents appeared in the concentration range from 0.05-0.6 μg/mL melamine standard, with an estimated LOD of 0.069 μg/mL and an average relative standard deviation of 8.0%. This indicated that the method could be considered as an alternative method for selective and quantitative immunochromatographic applications. The validity was examined by the measurements of melamine injected into milk samples, which showed good recovery percentages during the measurements.