exo- and enantioselective cycloaddition of azomethine ylides generated from N-alkylidene glycine esters using chiral phosphine-copper complexes

High diastereo- and enantioselectivities were obtained for the asymmetric 1,3-dipolar cycloaddition of azomethine ylides generated from N-alkylideneglycine esters with dipolarophiles using chiral phosphine-copper complexes as catalysts. Whereas the cycloaddition of azomethine ylides catalyzed by metal salts generally afforded endo-adducts as the predominant product, the present method is the first example of an exo-selective cycloaddition. [reaction: see text]     

Molecule-Responsive Fluorescent Sensors of α-Helix Peptides Bearing α-Cyclodextrin, Pyrene and Nitrobenzene Units in Their Side Chains

-Helix peptides bearing one unit of -cyclodextrin (-CD), one unit of pyrene and one unit of nitrobenzene (NB) in their side chains have been designed and synthesized as novel molecule-responsive devices.In both the CD-peptides, -PR17 and -PL17, the NB unit is separated from the CD unit by two turns of the helix. Two reference peptides (PL17, and -P17,) have also been synthesized. The circular dichroism studies in the peptide absorption region (200–250 nm)of -PR17 and -PL17 suggestthat the CD-peptides form stable-helixstructures (83–77%), which was destabilized by accommodating guest molecules (e.g., n-pentanol) into the CD cavity. It suggests that formation of intramolecular host–guest(CD–NB) complex stabilized thehelical structure and exogenous guest molecule excluded the appending NB moiety from inside to outside of the CD cavity, thereby causing destabilization of the helical structure and increasing the random coil content. The ICD spectra of the peptides in the pyrene and nitrobenzene absorption region (250–40 nm) suggest that NB forms inclusion complex with CD. The fluorescence studies revealed that the fluorescence of the pyrene unit is quenched by the NB unit in -PR17 and -PL17. The fluorescence intensity increases with increasing guest concentration for the CD-peptides.This guest-responsiveenhancement in the fluorescence intensity can be explained in terms of increased distance between the pyrene and NB moieties, which is caused by exclusion of the NB moiety from the CD cavity by guest accommodation. Using the guest-responsive fluorescence quenching properties of the CD-peptides, we have obtained binding constants for various short chain alkanols. -PL17 has higher binding affinity to the guest molecules than its isomer, -PR17, indicating that the location of functional groups on the peptide scaffold is important in molecule detection.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.     

Temperature stabilized optical waveguide modulator

A low drive-voltage optical modulator using a Ti-diffused UNbO₃ optical waveguide has been fabricated. Stabilization against ambient temperature change was realized by using a miniature halfwave plate. The halfwave voltage, 3 dB bandwidth, optical insertion loss and extinction ratio were 3·8 V (at 1·06m wavelength), 850 MHz, 10 dB and 13 dB, respectively. A reduction scheme for the optical absorption caused by metallic electrodes, and an analysis of the modulator high frequency response are also reported.     

Release from or through a wax matrix system. V. Applicability of the square-root time law equation for release from a wax matrix tablet

To obtain basic and clear release properties, wax matrix tablets were prepared from a physical mixture of drug and wax powder at a fixed mixing ratio. Properties of release from the single flat-faced surface, curved side surface, and/or whole surface of the wax matrix tablet were examined. Then tortuosity and the applicability of Higuchi's square-root time law equation were examined. The Higuchi equation well analyzed the release processes of different release manners. However, the region fitted to the Higuchi equation differed with the release manner. Tortuosity obtained with release from the single flat-faced surface and curved side surface was comparable with that obtained with the release from a reservoir device tablet, whereas tortuosity obtained with release from the whole surface was larger. As the wax matrix tablets were prepared at a fixed mixing ratio, their internal structures should be similar. Therefore changes in the matrix volume or volume fraction with release were examined, and an extra volume where dissolved drug stray becomes large with release time in the case of release from the whole surface. These factors should be taken into account for evaluation of applicability and release properties. Furthermore, the entire release process should be analyzed using a combination of the square-root time law and other suitable equations in accordance with release manner or condition.     

Release from or through a wax matrix system. IV. Generalized expression of the release process for a reservoir device tablet

Generalization of the release process through the wax matrix layer was examined by use of a reservoir device tablet. The wax matrix layer of the reservoir device tablet was prepared from a physical mixture of lactose and hydrogenated castor oil to simplify the release properties. Release through the wax matrix layer showed zero-order kinetics in a steady state after a given lag time, and could be divided into two stages. The first stage was the formation process of water channel by dissolving the soluble component in the wax matrix layer. The lag time obtained by applying the square root law equation was well connected with the amount of the matrix layer and mixed weight ratio of components in this layer. The second stage was the zero-order release process of drug in the reservoir through the wax matrix layer, because the effective surface area was fixed. The release rate constants were connected with thickness of the matrix layer and permeability coefficient, and the permeability coefficients were connected with the diffusion coefficient of drug and porosity. Hence the release rate constant could be connected with the amount of matrix layer and the mixed weight ratio of components in the matrix layer. It was therefore suggested that the release process could be generalized using the amount of matrix layer and the mixed weight ratio of components in the matrix layer.