Synthesis and in vitro evaluation of botryllazine B analogues as a new class of inhibitor against human aldose reductase

Botryllazine B analogues of diverse substitution patterns have been prepared, and their in vitro inhibitory activities against recombinant human aldose reductase (h-ALR2) evaluated. Among the 15 compounds tested, 6-(4-aminophenyl)-2-(4-hydroxyphenyl)carbonylpyrazine (7b) proved to be the most potent inhibitor, with IC₅₀=0.91 μM. Kinetic analyses of 7b and botryllazine B (1) revealed that these inhibitors exhibit an unprecedented mixed-type inhibition on h-ALR2 with respect to the substrate d,l-glyceraldehyde, in the presence of NADPH at inhibitor concentrations near the IC₅₀ values.     

Study of temperature-responsibility on the surfaces of a thermo-responsive polymer modified stationary phase

We investigated a thermo-sensitive polymer, poly(N-isopropylacrylamide) (PNIPAAm), which is the basis of an HPLC stationary phase. We prepared a PNIPAAm terminally-modified surface. In this study, we investigated the effect of PNIPAAm on the surface of a stationary phase on separation based on changes of the retention time with the temperature step gradient. As the temperature changed the surface property of the stationary phase switched from hydrophilic to hydrophobic. The retention on the polymer-modified stationary phase remarkably changed upon changing the temperature. Using a column packed with PNIPAAm-modified silica, the separation of steroids was carried out by changing the temperature. With increasing temperature, an increased interaction between solutes and PNIPAAm-grafted surfaces of the stationary phases was observed. A temperature-dependent resolution of steroids was achieved using only water as a mobile phase. The PNIPAAm-modified surface of the stationary phase exhibited temperature-controlled hydrophilic-hydrophobic changes. The drastic and reversible surface hydrophilic-hydrophobic property alteration for PNIPAAm terminally-grafted surfaces should be due to rapid changes in the polymer hydration state around the polymer's transition temperature. A solvent gradient elution-like effect could be achieved with a single mobile phase by programmed temperature changes during chromatographic runs. This system should be highly useful to control the function and property of the stationary phase for HPLC only by changing the temperature with an aqueous solvent.     

Sequential reaction intermediates in aliphatic C-H bond functionalization initiated by a bis(mu-oxo)dinickel(III) complex

The reaction of [Ni2(OH)2(Me2-tpa)2]2+ (1) (Me2-tpa = bis(6-methyl-2-pyridylmethyl)(2-pyridylmethyl)amine) with H2O2 causes oxidation of a methylene group on the Me2-tpa ligand to give an N-dealkylated ligand and oxidation of a methyl group to afford a ligand-based carboxylate and an alkoxide as the final oxidation products. A series of sequential reaction intermediates produced in the oxidation pathways, a bis(mu-oxo)dinickel(III) ([Ni2(O)2(Me2-tpa)2]2+ (2)), a bis(mu-superoxo)dinickel(II) ([Ni2(O2)2(Me2-tpa)2]2+ (3)), a (mu-hydroxo)(mu-alkylperoxo)dinickel(II) ([Ni2(OH)(Me2-tpa)(Me-tpa-CH2OO)]2+ (4)), and a bis(mu-alkylperoxo)dinickel(II) ([Ni2(Me-tpa-CH2OO)2]2+ (5)), was isolated and characterized by various physicochemical measurements including X-ray crystallography, and their oxidation pathways were investigated. Reaction of 1 with H2O2 in methanol at -40 degrees C generates 2, which is extremely reactive with H2O2, producing 3. Complex 2 was isolated only from disproportionation of the superoxo ligands in 3 in the absence of H2O2 at -40 degrees C. Thermal decomposition of 2 under N2 generated an N-dealkylated ligand Me-dpa ((6-methyl-2-pyridylmethyl)(2-pyridylmethyl)amine) and a ligand-coupling dimer (Me-tpa-CH2)2. The formation of (Me-tpa-CH2)2 suggests that a ligand-based radical Me-tpa-CH2* is generated as a reaction intermediate, probably produced by H-atom abstraction by the oxo group. An isotope-labeling experiment revealed that intramolecular coupling occurs for the formation of the coupling dimer. The results indicate that the rebound of oxygen to Me-tpa-CH2* is slower than that observed for various high-valence bis(mu-oxo)dimetal complexes. In contrast, the decomposition of 2 and 3 in the presence of O2 gave carboxylate and alkoxide ligands, respectively (Me-tpa-COO- and Me-tpa-CH2O-), instead of (Me-tpa-CH2)2, indicating that the reaction of Me-tpa-CH2* with O2 is faster than the coupling of Me-tpa-CH2* to generate ligand-based peroxyl radical Me-tpa-CH2OO*. Although there is a possibility that the Me-tpa-CH2OO* species could undergo various reactions, one of the possible reactive intermediates, 4, was isolated from the decomposition of 3 under O2 at -20 degrees C. The alkylperoxo ligands in 4 and 5 can be converted to a ligand-based aldehyde by either homolysis or heterolysis of the O-O bond, and disproportionation of the aldehyde gives a carboxylate and an alkoxide via the Cannizzaro reaction.     

Drastic difference in the photo-driven hydrogenation reactions of ruthenium complexes containing NAD model ligands

Successful control of photo-driven NAD(+)/NADH type hydrogenation reactions in ruthenium complexes has been accomplished by using a new NAD(+) model ligand with modulated distortion of the ligand taking advantage of the substituent effect.     

Formation and characterization of water-soluble hetero capsules derived from multiple ionic interactions

We now report the formation and characterization of water-soluble hetero-capsules 1·2 resulting from the ionic interactions between positively charged flexible aniline hydrochloride 1 and negatively charged phosphonate 2 having rigid homooxacalix[3]arene units. The formation of the molecular capsules was studied by NOESY, DOSY NMR spectroscopy and ESI-Mass spectrometry. The water solubility of the capsules is improved by the introduction of mono- or triethylene glycol substituents in the homooxacalix[3]arene-based phosphonate units 2.     

Crystallization behavior and origin of c-axis orientation in sol–gel-derived ZnO:Li thin films on glass substrates

Preferentially, c-axis-oriented lithium-doped zinc oxide (ZnO:Li) thin films were prepared on Pyrex borosilicate glass substrates by a sol–gel method starting from zinc acetate dihydrate, lithium chloride, 2-methoxyethanol and monoethanolamine. Decomposition and crystallization behavior of dip-coated amorphous precursor films during post-annealing treatments were investigated by thermogravimetry–differential thermal analysis (TG–DTA), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), optical transmittance measurements, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). It was revealed that the films contained the organic compounds at temperatures up to 300°C, which was the key to the transformation from the amorphous to the crystalline state. Thermodynamical consideration of nucleation and crystal growth was made taking account of surface energies of the film and the glass substrate and an interfacial energy between them. Mechanisms underlying the c-axis orientation were proposed based upon the initial orientation due to nucleation and final growth orientation.     

Magnetization and torque measurements on Nd2Fe14B single crystals

Magnetization and torque measurements on single crystal specimens of Nd₂Fe₁₄B have been carried out. The magnetization values measured always in the direction of easy magnetization and those in the [001] direction have been precisely determined at temperatures from 4.2K to 600K with a superconducting magnet up to 52.65 kOe. Below the spin reorientation temperature 135K, the magnetization value of the direction of easy magnetization increases anomalously with decreasing temperature. The direction of easy magnetization tilts from the [001] axis to the [110] axis and this tilt angle has been also precisely determined by torque measurement in the temperature range below the spin reorientation temperature. The four-fold symmetry in torque curve for the (001) plane is continously observed at even up to near room temperature and the [110] direction of easy magnetization and the [100] direction of hard magnetization do not change below and above the spin reorientation temperature.     

High-resolution capability of optical near-field imprint lithography

We propose a novel method to increase the resolution of imprint lithography by introducing strong localization of the optical near-field intensity, depending on the mold structure. By optimizing the thickness of the metallic film on a SiO₂ line-and-space (LS) mold without a sidewall coating, we confirmed that the optical near-field strongly localizes at the edge of the mold, using a finite-difference time-domain calculation method. Based on the calculated results, we performed optical near-field imprint lithography using a mold with metallized (20-nm-thick Al without a sidewall coating) SiO₂ LS with a 300-nm half-pitch that was 200-nm deep with illumination using the g-line (λ=436 nm), and obtained features as narrow as 50 nm wide. PACS 81.16.Nd; 81.16.Rf     

Structures and chromatographic characteristics of capsule-type silica gels coated with hydrophobic polymers in reversed-phase liquid chromatography

Summary Silicone polymer-coated silica gels modified with octadecyl and octyl groups (S/S-C₁₈, S/S-C₈), or “capsule-type silica gels” were developed as packing materials for reversed-phase liquid chromatography. They were obtained by coating the surface of totally porous silica gel with a homogeneous silicone polymer film, and thereafter modifying the coating polymer with octadecyl or octyl groups. Retaining the advantages of silica-based packings, they show strong resistance of alkali-like organic porous polymeric materials.     

One step synthesis of aziridines by the Michael type addition of free sulfimides: Preparation and absolute configuration of optically active acylaziridines

The Michael type additions of diphenyl N-unsubstituted sulfimide (free sulfimide) to various electrophilic olefins were carried out. The reaction with cis- and trans-dibenzoylethylene, dimethyl-fumarate, dimethylmaleate, benzalacetophenone and benzalacetone gave mainly the corresponding trans-2-acylaziridines and trans-enaminoketones. However, phenyl vinyl sulfone or acrylonitrile afforded not the corresponding aziridine but diphenyl-N-2-cyano or N-2-phenylsulfonylethylsulfimide, a simple Michael adduct When optically active (+)-(R)-o-methoxyphenyiphenyl free sulfimide was treated with such an α,β-unsaturated carbonyl compound as benzalacetopbenone, an optically active 2-acylazindine, i.e., (-)-trans-2-benzoyl-3-phenylaziridine was obtained in ca 30% optical purity and its absolute configuration was assigned as (2R,3S) upon chemical transformation to the configuration-ally known 2-phenyl-2-benzoylamino-1-ethanol or by comparing its CD spectrum with that of (1R,2R)-1-phenyl-2-benzoyl-cyclopropane. Meanwhile, (-)-(S)-o-methoxyphenylphenyl free sulfimide was found to react with benzalacetophenone to afford (+)-trans-2-benzoyl-3-phenylaziridine of 25% optical purity. Effects of solvent and temperature on both die distribution of the products ratio and the optical yield were examined.