Total Syntheses and Chemical Biology Studies of Hymeglusin and Fusarilactone A,Novel Circumventors of β-Lactam Drug Resistance in Methicillin-Resistant Staphylococcus aureus

Hymeglusin, a previously known eukaryotic hydroxymethylglutaryl-CoA (HMG−CoA) synthase inhibitor, was identified as circumventing the β-lactam drug resistance in methicillin-resistant Staphylococcus aureus (MRSA). We describe the concise total syntheses of a series of natural products, which enabled determination of the absolute configuration of fusarilactone A and provided structure-activity relationship information. Based on previous reports, we speculated that the target protein of this circumventing effect may be MRSA bacterial HMG−CoA synthase (mvaS). We found that this enzyme was dose-dependently inhibited by hymeglusin. Furthermore, overexpression of the MRSA mvaS gene and site-directed mutagenesis studies suggested its binding site and the mechanism of action.     

High sensitive immunoassay for endocrine disrupting chemicals using antibody immobilized microcapillary bundle structure

We proposed and fabricated a new chemical reactor with a vertical fluid flow operation for the wide biochemical applications. For rapid and high-yield reaction between reagents with large quantity, the filters, which possess 2,100 cylindrical through-bores were fabricated by deep X-ray lithography using synchrotron radiation. First, we tried the application of the fabricated vertical reactor to a sandwich enzyme-linked immunosorbent assay for the analysis of mouse immunoglobulin and nonylphenol using ultra violet absorption spectroscopy. We also confirmed the possibility of the analysis methods for competitive enzyme-linked immunosorbent assay of an endocrine disrupter, nonylphenol in a series of vertical fluidic operation. This sensitivity was one order higher than the sensitivity obtained by ordinary enzyme-linked immunosorbent assay using 96-wells microtiter plate and the same anti-NP-antibody.     

Photochromic Diarylethene Derivatives Bearing Hydrophilic Substituents

Photochromic diarylethene derivatives bearing hydrophilic N,N-bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)sulfonamide (SO₂NTEG₂) ( 1 – 3 ) or myo-inositol ( 4 – 6 ) substituents were synthesized. Although the solubility in aqueous solution of the derivatives containing the four tri(ethylene glycol) chains was relatively poor, the solubility was improved by introducing two myo-inositol residues. The derivatives could be dissolved even in pure water and underwent photochromism upon alternate irradiation with ultraviolet (UV) and visible light, in both organic and aqueous solutions. The absorption maxima of the open- and closed-ring isomers of these derivatives and the photostationary conversion ratios from the open- to the closed-ring isomers upon UV irradiation did not change much, even when the solvent polarity was changed. These results indicate that the diarylethene derivatives are mono-molecularly dissolved in aqueous solution and that intermolecular interactions between the derivatives are negligible when the concentration is less than 1×10⁻⁴ mol⋅L⁻¹.     

Xanthine Oxidase Inhibitory Activity and Hypouricemic Effect of Aspalathin from Unfermented Rooibos

Rooibos is rich in flavonoids such as aspalathin, which is a unique C‐glycosyl dihydrochalcone, that is used as a traditional herbal tea. This study was designed to evaluate the in vitro xanthine oxidase (XOD) inhibitory activity of the aspalathin‐rich fraction (ARF) and purified aspalathin from rooibos. The hypouricemic effects of the ARF and aspalathin on hyperuricemic mice were also assessed. The ARF was prepared from aqueous extract of unfermented rooibos leaves and stems, and it was collected by column chromatography; the aspalathin content in this fraction was 21.4%. The ARF and aspalathin inhibited XOD in a dose‐dependent manner. The concentrations of the ARF and aspalathin required to inhibit XOD at 50% (IC₅₀) were 20.4 μg/mL (4.4 μg/mL aspalathin equivalents) and 4.5 μg/mL, respectively. Lineweaver–Burk plot analysis indicated that aspalathin was a competitive inhibitor of XOD, and the inhibition constant (Ki) was 3.1 μM. In hyperuricemic mice induced by inosine‐5’‐monophosphate, treatment with the ARF and aspalathin significantly suppressed the increased plasma uric acid level in a dose‐dependent manner. The suppressed plasma uric acid level in mice could be attributed to the XOD inhibitory activity of the ARF and aspalathin. Further study is required to determine the effect of aspalathin or its metabolites on XOD activity in vivo.     

Stability tests of quadrupole mass spectrometer by two-stage flow-dividing system

Stability tests of two quadrupole mass spectrometers (QMSs) were performed using a two-stage flow-dividing system from the following viewpoints: (1) fluctuation and drift of ion current, (2) repeatability of ion current, (3) change in ion current owing to prior conditions of use, (4) long-term stability of sensitivity, and (5) interference effect. These tests were performed at the pressure from 8 × 10⁻⁶ Pa to 8 × 10⁻⁴ Pa using N₂, Ar, He, and H₂.The fluctuation and drift of two QMSs over 1 h were within 2%. The repeatabilities at pressures of 8 × 10⁻⁶ Pa and 8 × 10⁻⁵ Pa were within 2% during eight cycles with an interval of 1 h between each cycle. However, the repeatability at 8 × 10⁻⁴ Pa increased to be within 4%. The changes in sensitivities of QMS-1 and QMS-2 for 757 days were less than ±15% and less than ±25%, respectively. The change owing to the interference effect was less than 2% while the partial pressure of the interference gas was under 2 × 10⁻⁴ Pa. However, both positive and negative changes were observed less than 60% with increasing the partial pressure of the interference gas until 8 × 10⁻³ Pa.     

Incorporation of nonionic emulsifiers inside styrene–methacrylic acid copolymer particles during emulsion copolymerization

Emulsion copolymerizations of styrene and methacrylic acid with polyoxyethylene nonylphenyl ether nonionic emulsifiers having various hydrophilic–lipophilic balance (HLB) values (13.7, Emulgen 911; 15.5, Emulgen 920; 17.2, Emulgen 931) were performed. The incorporation behavior of the nonionic emulsifiers, comprising polydisperse poly(ethylene oxide) (PEO) chain lengths, inside the particles was investigated. At the completion of the polymerization, the incorporated percentage of the lowest HLB emulsifier was 61%, much higher than that of the highest HLB one (10%). In both polymerizations, the amounts of the incorporated emulsifiers increased with conversion, and shorter PEO chain (i.e., lower molecular weight) components were predominantly incorporated over longer PEO chain components.     

Use of compact shield tunneling method in urban underground construction

In Tokyo Metropolis, the rehabilitation and renewal of sewer systems is an urgent issue due to the aged sewers and increases in wastewater and stormwater runoff. In such urban area, shield tunneling confronts various problems, such as high construction costs, adverse effects on living environments, and densely used surface and underground spaces. To solve these problems, the authors developed a new shield tunneling method, which is called the “compact shield” method. This paper describes the concepts used for the construction of shield sewer tunnels without inner linings and an overview of the segments and a shield machine that were newly developed.     

Performance enhancement of polybenzoxazine by hybridization with polysiloxane

Polybenzoxazine-polydimethylsiloxane (PBa-PDMS) hybrids were successfully prepared in situ by the ring-opening polymerization of benzoxazine (Ba) and the sol-gel process of diethoxydimethylsilane (DEDMS). The reaction conditions were optimized, and homogeneous opaque hybrid films were obtained up to 13 wt% of PDMS content by using p-toluenesulfonic acid as the catalyst for sol-gel process. The domain size of PDMS in the PBa matrix was examined by SEM. The tensile strength and elongation at break of the PBa-PDMS hybrid films were higher than those of pristine PBa, because of the toughening effect of PDMS. Dynamic viscoelastic analysis showed that the glass transition temperature of the hybrid was also higher than that of pristine PBa. Moreover, the decomposition temperatures and weight residue at 850 °C increased with the increase of PDMS content as evidenced by thermogravimetric analysis.