Preparation and biological activity of 2-[4-(thiazol-2-yl)phenyl]propionic acid derivatives inhibiting cyclooxygenase.

A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with alpha-bromoaldehyde diethyl acetals or alpha-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R1) of the benzene ring and a methyl group in position 4 (R2) and/or 5 (R3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R1.     

Enantioseparation of chiral aromatic amino acids by capillary electrophoresis in neutral and charged cyclodextrin selector modes

Simultaneous enantioseparations of 15 racemic aromatic amino acids and L-mimosine for their chiral discrimination were achieved by neutral selector-modified capillary electrophoresis (CE) and by charged selector-modified CE. Among the diverse cyclodextrins (CDs) examined, hydroxypropyl (HP)-alpha-CD as the neutral selector and highly sulfated (HS)-gamma-CD as the charged selector provided best chiral environments of different enantioselectivities. Fairly good enantiomeric resolutions were achieved with the HP-alpha-CD mode except for racemic 6-hydroxy-3,4-dihydroxyphenylalanine, threo-3,4-dihydroxyphenylserine and homophenylalanine while high-resolution separations of all the enantiomeric pairs were achieved in the HS-gamma-CD mode except that L-mimosine was not detected and a partial resolution (0.6) for threo-3,4-dihydroxyphenylserine enantiomers. Relative migration times to that of internal standard under the respective optimum conditions were characteristic of each enantiomer with good precision (% RSD: 0.7-3.8), thereby enabling to cross-check the chemical identification of aromatic amino acids and also their chiralities. The method linearity was found to be adequate (r> 0.99) for the chiral assay of the aromatic amino acids investigated. When applied to extracts of three plant seeds, nonprotein amino acids such as L-mimosine (42 nug/g) from Mimosa pudica Linné, and L-3,4-dihydroxyphenylalanine (268 nug/g) from Vicia faba were positively detected along with L-tryptophan, L-phenylalanine and L-tyrosine.     

Preparation of antipyretic analgesic by direct compression and its evaluation

Direct compression is able to produce tablets at a lower cost than wet granulation and tableting method, due to a fewer items of process validation. In this study, acetaminophen was used as a medicine with various granular diameters to formulate tablets by direct compression, thus evaluating their physical properties. Consequently, direct compression was found effective in formulating tablets with excellent physical properties, with the granular diameter taken into account. It was confirmed that tablets produced by direct compression were similar in physical properties in tablets produced by wet granulation and tableting method. Further, it was suggested that use of a dry-type binder would make it possible to provide a tablet having higher content of the medicine with excellent physical properties.     

Fluorescence studies on phenylene moieties embedded in a framework of periodic mesoporous organosilica

The excited state characteristics of phenylene (Ph)-bridged periodic mesoporous organosilica (PMO) powders with crystal-like and amorphous wall structures are investigated. Crystal-like Ph-PMO has a molecular ordering of the bridging organic moieties with intervals of 0.76 and 0.44 nm parallel and perpendicular to the mesochannel direction, respectively, whereas amorphous Ph-PMO has no molecular-level periodicity in the wall. Fluorescence from the exciton and excimer of the Ph moieties and the defect center in the silicate network were detected at room temperature, but fluorescence from the excimer and the defect center were not detected at 77 K for crystal-like Ph-PMO dispersed in a methanol/ethanol mixed solvent. The decay curve of the exciton fluorescence of crystal-like Ph-PMO at room temperature was analyzed successfully using a one-dimensional diffusion model quenched by the defect center and the excimer site. The results were discussed in comparison with those for the crystal-like biphenylene-bridged PMO reported in the preceding paper (Yamanaka et al., Phys. Chem. Chem. Phys., 2010, 12, 11688-11696). The existence of excited states with various conformations including ground state dimers or aggregates of the Ph moieties was suggested for amorphous Ph-PMO. It was clearly apparent that the differences in the excited state dynamics reflected the differences in the molecular-level structure in the wall.     

Solid state reaction synthesis of filled skutterudite compounds (Ce or Y)yFexCo4-xSb12 and the effect of filling atoms Ce or Y on lattice thermal conductivity

The synthesis of filled skutterudite compounds (Ce or Y)_y(Fe)_x(Co)_(4x)(Sb)_(12), through a solidstate reaction using chloride of Ce or Y,high purity powder of Co, Fe, and Sb as starting materials,was investigated. (Ce or Y)_y(Fe)_x(Co)_(4x)(Sb)_(12) (x=0--1.0, y=0--0.15) compounds were obtained at850--1 123 K. The results of Rietveld analysis demonstrate that (Ce or Y)_y(Fe)_x(Co)_(4x)(Sb)_12synthesized by a solid state reaction possesses a filled skutterudite structure. The filling fraction ofCe or Y obtained by Rietveld analysis agrees well with the composition obtained by chemicalanalysis. The lattice constant of (Ce)_y(Fe)_x(Co)_(4x)(Sb)_(12) increases with increasing substitution of Fe at Cosites, and with an increasing Ce filling fraction in the Sb-dodecahedron voids. The lattice thermalconductivity of (Ce or Y)_y(Fe)_x(Co)_(4x)(Sb)_(12) decreases significantly with an increasing Ce or Y fillingfraction in the voids and with substitution of Fe at Co sites.     

The crystallographic structure of the natural air-hydrate in Greenland dye-3 deep ice core

We have carried out X-ray diffraction studies on single crystals of natural air-hydrate in deep ice cores recovered at Dye-3 Greenland. Integrated intensities for 470 diffracting planes were measured by an automated four-circle diffractometer. The space group determined is cubicFd3m and the lattice constant is 17.21(3) Å. These results indicate that the crystallographic structure is the Stackelberg's structure II, in contrast to the previously anticipated structure. This finding agrees with the recent results on the synthetic air-hydrate by Davidsonet al. It was also found by difference Fourier synthesis for guest molecules that electron density in a 16-hedral cage has multiple maxima displaced from the center of the cage while that in the 12-hedron was approximately spherical.Dedicated to Dr D. W. Davidson in honor of his great contributions to the sciences of inclusion phenomena.     

Fused silica capillary tube isotachophoresis using a multichannel photodiode array detector

Isotachophoresis carried out in a 0.25 mm i.d. fused-silica capillary tube yielded high resolution, compared with that in a fluorinated ethylene-propylene polymer tube. The use of an ultraviolet-visible multichannel spectrophotometer with photodiode array as detector together with a cross flow cell (volume 0.01 μl) was investigated. The system was successfully applied to the analysis of cationic dyes such as neutral red, bismarck brown, and basic fuchsine.     

Formation of cyclic organosilicon compounds via organopolysilyl anions starting from methoxymethyldisilanes. A mechanistic study

In the presence of a catalytic amount of sodium methoxide, sym-dimethoxytetramethyldisilane was converted into α,ω-dimethoxypermethylpolysilanes, MeO(SiMe₂)_nOMe where n ? 3, at room temperature. On the other hand, similar treatment of the disilane in THF solution gave cyclic polysilanes, (Me₂Si)_n where n = 5–7. Decomposition of the disilane in the presence of diphenylacetylene afforded a trisilacyclopentene derivative under similar conditions. This compound was obtained also by the reaction between α,ω-dimethoxypermethylpolysilanes and diphenylacetylene in the presence of sodium methoxide. These cyclic products most likely were formed via permethyl polysilyl anion intermediates derived from α,ω-dimethoxypermethylpolysilanes. Also, the formation of α,ω-dimethoxypermethylpolysilanes could be elucidated in terms of the mechanism involving the base-assisted, concerted nucleophilic substitution or stepwise substitution by silyl anions, rather than the successive dimethylsilylene (Me₂Si:) insertion reaction.     

Inhibitory effects of 3-O-acyl-(+)-catechins on Epstein-Barr virus activation

In the course of an exploratory investigation of antitumor-promoting catechins, 3-O-acyl-(+)-catechins of varying carbon lengths from C(4) to C(18) were assessed for inhibitory effects on the activation of the Epstein-Barr virus early antigen. Like 3-O-acyl-(-)-epigallocatechins, the (+)-catechin derivatives showed promising effects with the C-3 acyl chain of C(8)-C(11) carbon atoms.