Improved cross-axis synchronous flow-through coil planet centrifuge for performing counter-current chromatography. II. Studies on retention of stationary phase in short coils and preparative separations in multilayer coils

Performance of the apparatus was evaluated in terms of stationary phase retention, partition efficiency and sample loading capacity. Preliminary studies with short coils revealed high retention of the stationary phase under a proper combination of the head-tail elution and planetary motion. Preparative capability of the apparatus was successfully demonstrated on efficient multigram separations of 2,4-dinitrophenyl amino acids, indole auxins, and bacitracin in a pair of large multilayer coils with a total capacity of 1.5 l.     

Experimental observations of the hydrodynamic behavior of solvent systems in high-speed counter-current chromatography. II. Phase distribution diagrams for helical and spiral columns

Extensive studies have been performed on hydrodynamic distribution of two immiscible solvent phases in helical and spiral columns by means of coil planet centrifugation. Under the Scheme IV [see Fig. 1 in Y. Ito, J. Chromatogr., 301 (1984) 377] planetary motion, the two phases display unilateral distribution in the coil, i.e., one phase travels toward the head and the other phase toward the tail. This hydrodynamic trend is sensitively affected by various factors such as physical properties of the solvent system, helical diameter of the column, revolutional radius, etc. Phase distribution diagrams obtained from a set of conventional two-phase solvent systems under various experimental conditions provide extremely useful information for both basic hydrodynamic studies and practical application in high-speed counter-current chromatography.     

Synthesis and characterization of flavylium salts having three types color depending on recrystallization conditions

Three types of flavylium salts (FVs, yellow, green and red) have been synthesized and the colors depended on recrystallization conditions. The existence of these color states was confirmed by diffuse reflectance spectra. The spectra were almost the same as the absorption spectra in ethanol solution. The molecular state of FVs in crystals will be the same as that in solutions. The crystal colors of the FVs are controlled by the recrystallization conditions.     

Studies on antiallergic agents. I. Synthesis and antiallergic activity of novel pyrazine derivatives.

Various pyrazine derivatives were synthesized and their antiallergic activity was examined. The inhibitory activity on allergic histamine release of the compounds bearing a 5-tetrazolyl group was more potent than that of the corresponding carboxyl derivatives. The introduction of -CONH- or -NHCO- between the pyrazine ring and the 5-tetrazolyl group as a spacer greatly enhanced the activity. N-(1H-Tetrazol-5-yl)-2-pyrazinecarboxamide (I-3) was estimated to exhibit nearly the same potency as disodium cromoglycate (DSCG). The structure-activity relationship among various derivatives modified by introducing some substituents onto the 3-, 5- or 6-position of the pyrazine ring of I-3 was investigated. The activity remained unchanged or was reduced when such substituents as methyl, chloro, methoxy, methylamino and dimethylamino were introduced at the 3- or 5-position. In contrast, 6-substitution with various alkylamino groups more or less increased the activity. Among them, the 6-dimethylamino (I-17c) and 6-(1-pyrrolidinyl) (I-34) derivative were proved to be most potent. The IC50 values (concentration which produces 50% inhibition of the allergic histamine release) of I-17c and I-34 were determined to be 4.7 x 10(-10) and 4.6 x 10(-10) M, respectively. These two compounds produced a potent inhibitory activity on passive cutaneous anaphylaxis (PCA) in rat, not only by the intravenous route (ED50 = 0.0096 mg/kg for both compounds) but also by the oral route (ED50 = 0.19 and 0.18 mg/kg, respectively). On the other hand, when the pyrazine ring of some representative compounds was replaced with a pyridine ring, the inhibitory activity on histamine release was significantly reduced.     

SPECIFIC PHOTOCOUPLING OF 5-BROMOURIDINE TO TRYPTOPHAN IN AQUEOUS FROZEN SOLUTION§

Abstract —5-Bromouridine (BrUd) photochemically reacted with l -tryptophan (trp) only in aqueous frozen solution giving rise to 2-[1,2,3,4-tetrahydro-1-(β-d -ribofuranosyl)-2,4-dioxo-5-pyrimidinyl]-l -tryptophan ( 1a ). Under similar conditions irradiation of 5-bromouracil (BrU) and trp gave the corresponding coupled product 2. Addition of acetone, potassium carbonate or sodium chloride to the frozen system completely inhibited the photocoupling reaction. These photocoupling reactions are suggested to proceed via mixed aggregate formation between trp and BrUd (or BrU) in frozen aqueous solution. Stacking interactions in these aggregates are characterized by an efficient quenching of trp fluorescence by BrUd. Under the same conditions other amino acids such as phenylalanine, tyrosine, histidine and lysine did not react with BrUd, indicating that the photocoupling of BrUd (or BrU) is specific for trp.     

Copolymerization of 1,6-anhydro-ß-D-galactopyranose and 1,6-anhydro-ß-D-mannopyranose derivatives

1,6-Anhydro-2,3,4-tri-O-(p-methylbenzyl)-ß-D -galactopyranose (TXGal,M₁) has been copolymerized with 1,6-anhydro-2,3,4-tri-O-benzyl-ß-D -mannopyranose (TBMan,M₂), the products characterized by NMR, specific rotation, and viscosity, and the reactivity ratios calculated. The reactivity ratios r₁ = 0.37 ± 0.15 and r₂ = 38 ± 4 indicate that the anhydromannose derivative is about 100 times as reactive as that of anhydrogalactose. A comparison of glucose, mannose, and galactose copolymerizations suggests that the reactivity differences of the three propagating cations are comparatively small and the reactivity differences of the monomers large. This result is consistent with a mechanism proposed earlier. Methyl substitution on the aromatic rings of the p-xylyl groups inhibits the initiation process significantly relative to benzyl, but propagation only slightly.     

Dependence of molecular recognition of fullerene derivative on the adlayer structure of zinc octaethylporphyrin formed on Au(100) surface

Adlayers of ZnOEP were prepared on reconstructed Au(100)-(hex) and unreconstructed Au(100)-(1 x 1) surfaces by immersing into a benzene solution containing ZnOEP molecules, and the adlayer structures were characterized by scanning tunneling microscopy (STM). A hexagonally arranged ZnOEP array was formed on an Au(100)-(hex) surface, whereas a rectangularly arranged ZnOEP array was found on an Au(100)-(1 x 1) surface. The adlayer structure of ZnOEP was dependent upon the underlying Au atomic arrangements. Furthermore, an investigation of the spuramolecular assembly for these modified surfaces was carried out by using an open-cage C(60) derivative (opened C(60)). A supramolecular assembled adlayer with a 1:1 composition of opened C(60)/ZnOEP was formed on Au(100)-(hex), whereas aggregates of opened C(60) were found on the ZnOEP-modified Au(100)-(1 x 1) surface. Electrochemical responses of opened C(60) were significantly influenced by underlying ZnOEP arrays. This finding suggests that precise control of underlying ZnOEP adlayers with the Au atomic structure is important to recognize the opened C(60) on them.     

Novel method to control release of lipophilic drugs with high potency from silicone

Silicone has been utilized as a carrier material for sustained release system of lipophilic drugs. Extensive studies revealed that drug release rate is influenced by factors such as physicochemical properties of the drug and additives.(1-5)) When a lipophilic drug is highly potent at low concentrations, the drug release rate should be strictly controlled so as to avoid side effects. In this study, using vitamin D(3) (VD(3)) as an example of such drugs, we investigated novel method to suppress initial burst and to modify drug release rate from silicone matrix. As a result, it was found that (a). addition of human serum albumin (HSA) suppressed initial burst and enhanced release rate in the later stage, resulting constant release of VD(3), (b). covering a matrix formulation with a membrane of low diffusivity (core-rod formulation) suppressed initial burst and released drug in a constant rate, and (3) using materials for which the drug has high affinity as dissolution solvent (reservoir formulation), the drug release rate was reduced.     

Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives.

To find a novel alpha-blocker with high alpha-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking selectivity as well as potent alpha-blocking activity.     

Singlet Oxygen–mediated Hydroxyl Radical Production in the Presence of Phenols: Whether DMPO–·OH Formation Really Indicates Production of ·OH?¶

The reaction of singlet oxygen (1O2) generated by ultraviolet-A (UVA)-visible light (lambda > 330 nm) irradiation of air-saturated solutions of hematoporphyrin with phenolic compounds in the presence of a spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), gave an electron spin resonance (ESR) spectrum characteristic of the DMPO-hydroxyl radical spin adduct (DMPO-*OH). In contrast, the ESR signal of 5,5-dimethyl-2-pyrrolidone-N-oxyl, an oxidative product of DMPO, was observed in the absence of phenolic compounds. The ESR signal of DMPO-*OH decreased in the presence of either a *OH scavenger or a quencher of *O2 and under anaerobic conditions, whereas it increased depending on the concentration of DMPO. These results indicate both 1O2- and DMPO-mediated formation of free *OH during the reaction. When DMPO was replaced with 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO), no DEPMPO adduct of oxygen radical species was obtained. This suggests that 1O2, as an oxidizing agent, reacts little with DEPMPO, in which a strong electron-withdrawing phosphoryl group increases the oxidation potential of DEPMPO compared with DMPO. A linear correlation between the amounts of DMPO-*OH generated and the oxidation potentials of phenolic compounds was observed, suggesting that the electron-donating properties of phenolic compounds contribute to the appearance of *OH. These observations indicate that 1O2 reacts first with DMPO, and the resulting DMPO-1O2 intermediate is immediately decomposed/reduced to give *OH. Phenolic compounds would participate in this reaction as electron donors but would not contribute to the direct conversion of 1O2 to *OH. Furthermore, DEPMPO did not cause the spin-trapping agent-mediated generation of *OH like DMPO did.