Stabilized liposomes with phospholipid polymers and their interactions with blood cells

To stabilize a phospholipid liposome, addition of various water-soluble polymers into a liposomal aqueous suspension was investigated. The water-soluble polymers were poly(ethylene oxide) (PEO), poly(N-vinyl pyrrolidone) (PVPy) and poly[2-methacryloyloxyethyl phosphorylcholine(MPC)], and poly[MPC-co-n-butyl methacrylate(BMA)]. The gel–liquid crystal transition temperature (T_c) of the diparmitoylphosphatidylcholine (DPPC) liposome was not changed by addition of these polymers significantly. However, membrane fluidity of DPPC liposome treated with water-soluble polymers, which was measured with fluorescence probe, depended on the chemical structure of the water-soluble polymers. In the case of PEO and PVPy, the temperature dependence of membrane fluidity was the same as that of the original DPPC liposome, on the other hand, poly(MPC) and poly(MPC-co-BMA) induced a rise in the temperature where an increase in the membrane fluidity was observed. The release of carboxy fluorescein from the DPPC liposome was suppressed by the addition of the MPC polymers. The liposomes in the MPC polymer solution were stable compared with those in water when plasma was added into the suspension. Interactions with stabilized liposome with blood cells such as platelets and erythrocytes were evaluated. Activation of platelets in contact with liposome covered with poly(MPC) or poly(MPC-co-BMA) was less than PEO-stabilized liposome. On the other hand, no hemolysis of erythrocytes was observed when every polymer-treated liposome was added in the suspension of erythrocytes. Based on these results, the MPC polymers could interact with the liposome surface, adsorb on the liposomes and stabilize them, and had no adverse effect to the blood cells even when they were in a physiological environment.     

Synthesis of 2-phenylbenzofuran derivatives as testosterone 5 alpha-reductase inhibitor

A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. Against rat enzyme, the carbamoyl derivatives had more potent inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6-carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives. Against human enzyme, the 6-substituted derivatives had more potent inhibitory activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino derivatives tended to show stronger inhibitory activities against human type 1 enzyme than against type 2 enzyme, but they were not largely selective.     

Stereoregularity of poly(vinyl ether)

α-Methylvinyl isobutyl and methyl ethers were polymerized cationically and the structure of the polymers was studied by NMR. Poly(α-methylvinyl methyl ether) polymerized with iodine or ferric chloride as catalyst was found to be almost atactic, whereas poly(α-methylvinyl isobutyl ether) polymerized in toluene with BF₃OEt₂ or AlEt₂Cl as catalyst was found to be isotactic. In both cases, the addition of polar solvent resulted in the increase of syndiotactic structure as is the case with polymerization of alkyl vinyl ether. tert-Butyl vinyl ether was polymerized, and the polymer was converted into poly(vinyl acetate), the structure of which was studied by NMR. A nearly linear relationship between the optical density ratio D₇₂₂/D₇₃₆ in poly(tert-butyl vinyl ether) and the isotacticity of the converted poly(vinyl acetate) was observed.     

Stereocontrolled,straightforward synthesis of 3-substituted methyl 7α-methoxy-1-oxacephems

Stereocontrolled and industrially feasible synthesis of a new antibiotic $\text{1a}$ and related derivatives, which is characterized by using all the carbon atoms of the penicillin skeleton, is described.     

Scale-up potential of ion-pair high-performance liquid chromatography method to produce biologically active inositol phosphates

This study was undertaken to evaluate the possibility that an analytical ion-pair HPLC procedure used to determine phytic acid (IP6) and its degradation products (IP3-IP5) can be transformed to a preparative purification method. A commercial phytic acid (CPA) preparation was separated into its component fractions of IP3, IP4, IPS, and IP6 on two C18 columns (1.8 and 4.2 ml) using 51% methanol containing 0.6-1% tetrabutylammonium hydroxide as ion-pair reagent and 0-0.025 M formic acid (pH 4.3) as eluent at 1.7 and 3.0 cm/min linear velocity, respectively, and 40 degrees C. Elution was monitored at 40 degrees C by a refractive index detector. Reproducible separation of CPA into four well-resolved peaks on these columns was possible after optimizing method variables, particularly the concentration of ion-pair reagent in the injected sample (>1.5%). The same separations were obtained after CPA loads were scaled up 25 times on a steel column (15 cm x 19 mm I.D.), packed with Ethyl C2 sorbent (10 microm) and on a 25 cm x 21.2 mm I.D. C18 column, but at a reduced linear velocity to increase the resolution. Therefore, this optimization of separation not only is useful for analysis of phytic acid and its degradation products but also it provides key parameters for scale up for further fractionation and characterization.     

Construction of on-line supercritical fluid extraction with reverse phase liquid chromatography–tandem mass spectrometry for the determination of capsaicin

A column-switching system, composed of supercritical fluid extraction (SFE) and reverse phase liquid chromatography/mass spectrometry (RPLC/MS) was constructed for on-line extraction and reverse-phase separation of capsaicinoids in capsicum fruits.     

A mechanistic study of the photoreaction of dimethylaniline and methyl chloroacetate: Role of acid-base properties in both the ground state and the excited state

On irradiation, dimethylaniline 1 reacted with methyl chloroacetate 2 in both acidic and basic solutions to yield methyl o- and p-dimethylaminophenylacetates (3a,3b). Kinetic treatments on the basis of quantum yields for fluorescence quenching and disappearance of 1 revealed the mechanism, which involves the exciplex in a broad sense under acidic conditions and both the exciplex and the charge-transfer complex under basic conditions.     

Le prolongement analytique de la solution du problème de Cauchy pour un certain opérateur différentiel à coefficients polynomiaux

In this article, we study analytic continuations of the solution of the Cauchy problem for a certain differential operator in the complex domain. à la mémoire de Jean Leray