Liposome modified with Mn-porphyrin complex can simultaneously induce antioxidative enzyme-like activity of both superoxide dismutase and peroxidase

An antioxidative liposome catalysis that mimics both superoxide dismutase (SOD) and peroxidase (POD) activities has been developed by using the liposomes modified with lipophilic Mn-(5,10,15,20-tetrakis[1-hexadecylpyridium-4-yl]-21H,23H-porphyrin) (Mn-HPyP). The SOD- and POD-like activities of the Mn-HPyP-modified liposome were first investigated by varying the type of phospholipid, such as 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC). Higher SOD-like activity was obtained in the case of DLPC and DMPC liposomes, in which the ligands were well-dispersed on the membrane in the liquid crystalline phase. The POD-like activity was maximal in the case of DMPC liposome, in which the Mn-HPyP complex was appropriately clustered on the membrane in the gel phase. On the basis of the above results, the co-induction of the SOD and POD activities to eliminate the superoxide and also hydrogen peroxide as a one-pot reaction was finally performed by using the Mn-HPyP-modified DMPC liposome, resulting in an increase in the efficiency of the elimination of both superoxide and hydrogen peroxide.     

Magnetically Alignable Bicelles with Unprecedented Stability Using Tunable Surfactants Derived from Cholic Acid

Five novel surfactants were prepared by modifying the three hydroxy groups of sodium cholate with triethylene glycol chains endcapped with an amide ( SC‐C₁ , SC‐ ⁿ C₄ , and SC‐ ⁿ C₅ ) or a carbamoyl group ( SC‐O ⁿ C₄ and SC‐O ^t C₄ ). The phase behavior of aqueous mixtures of these surfactants with 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphatidylcholine (DMPC) was systematically studied by ³¹P NMR spectroscopy. The surfactants endcapped with carbamate groups ( SC‐O ⁿ C₄ and SC‐O ^t C₄ ) formed magnetically alignable bicelles over unprecedentedly wide ranges of conditions, in terms of temperature (from 21–23 to >90 °C), lipid/surfactant ratio (from 5 to 8), total lipid content (5–20 wt %), and lipid type [DMPC, 1,2‐dilauroyl‐sn‐glycero‐3‐phosphatidylcholine (DLPC), or 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphatidylcholine (POPC)]. In conjunction with appropriate phospholipids, the carbamate‐endcapped surfactants afforded unique bicelles, characterized by exceptional thermal stabilities (from 0 to >90 °C), biomimetic lipid compositions (DMPC/POPC=25:75 to 50:50), and extremely large ²H quadrupole splittings (up to 71 Hz).     

Electronic Transitions in Conformationally Controlled Peralkylated Hexasilanes

The photophysical properties of oligosilanes show unique conformational dependence due to σ‐electron delocalization. The excited states of the SAS, AAS, and AEA conformations of peralkylated n‐hexasilanes, in which the SiSiSiSi dihedral angles are controlled into a syn (S), anti (A), or eclipsed (E) conformation, were investigated by using UV absorption, magnetic circular dichroism (MCD), and linear dichroism spectroscopy. Simultaneous Gaussian fitting of all three spectra identified a minimal set of transitions and the wavenumbers, oscillator strengths, and MCD B terms in all three compounds. The results compare well with those obtained by using the symmetry‐adapted‐cluster configuration interaction method and almost as well with those obtained by time‐dependent density functional theory with the PBE0 functional. The conformational dependence of the transition energies and other properties of free‐chain permethylated n‐hexasilane, n‐Si₆Me₁₄, was also examined as a function of dihedral angles, and the striking effects found were attributed to avoided crossings between configurations of σσ* and σπ* character.     

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.     

Mass transfer of weak acid in nanometer-sized pores of octadecylsilyl-silica gel

The sorption of bromophenol blue or anthracene-9-carboxylic acid as a weak acid into single octadecylsilyl (ODS)-silica gel microparticles in a solution was analyzed by microcapillary injection-manipulation and absorption microspectroscopy. The distribution ratio and the sorption rate were highly dependent on the pH of the solution. These results are discussed in terms of the acid dissociation/association, distribution between the ODS and solution phases, and intraparticle diffusion of the weak acid in the nanometer-sized pores of the ODS-silica gel.     

Concise total synthesis of (-)-spongotine A

The first asymmetric total synthesis of spongotine A is described. The oxidative synthesis of the imidazoline/ketone unit from keto aldehyde and diamine is a key step in this synthesis. The absolute stereochemistry of the asymmetric center of natural spongotine A is revealed as the (S)-configuration.     

Structure of the electrical double layer on the aqueous solution side of the polarized interface between water and a room-temperature ionic liquid, tetrahexylammonium bis(trifluoromethylsulfonyl)imide

The structure of the electrical double layer on the aqueous solution side has been studied by measuring electrocapillary curves at the polarized interface between a room-temperature ionic liquid (RTIL), tetrahexylammonium bis(trifluoromethylsulfonyl)imide, and water (W) at different concentrations of LiCl. Thermodynamic analysis of the electrocapillary curves indicates that Li+ ions negatively adsorb at the point of zero charge. The adsorption of Li+ and Cl- ions in the polarized potential window of about 200 mV can be explained by the Gouy's double layer model, and the specific adsorption of Li+ and Cl- ions at the RTIL|W interface is negligible within the polarized potential window.     

Phosphatidylcholine vesicle-mediated decomposition of hydrogen peroxide

The decomposition of hydrogen peroxide (H2O2) was examined in aqueous solution (50 mM Tris-HCl buffer, pH 7.4, containing 100 mM NaCl) at 25 degrees C in pure buffer or in the presence of either vesicles or micelles formed from various phosphatidylcholines (PCs). In the absence of PCs, more than 90% of the initially added H2O2 (1.0 mM) remained intact after incubation for 120 h. The effect of the PCs on the decomposition of H2O2 was studied by using different PCs that varied in terms of number of carbon atoms in the two acyl chains n as well as in terms of the degree of unsaturation. PCs with short hydrocarbon chains (n = 4, 6-8) were dissolved in the buffer solution in the form of nonassociated monomers or as micelles in equilibrium with monomers at a fixed PC concentration of 10 mM. The presence of these short-chain PCs slightly enhanced the H2O2 decomposition rate. Micelles formed by non-lipid detergents (sodium cholate, Triton X-100, and sodium dodecylsulfate) had a similar effect. In marked contrast, PCs with long hydrocarbon chains (n > or = 10) dispersed in buffer solution as vesicles (liposomes) significantly enhanced the rate of H2O2 decomposition, with the most effective PC being 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at 25 degrees C. This indicates that the packing density of the PC molecules influences the reactivity, presumably through the direct interaction of the PC assemblies with H2O2 molecules. Furthermore, in the case of vesicles formed from PCs with unsaturated acyl chains (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC; 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC), carbon-carbon double bond oxidation did not occur extensively under the conditions used. This indicates that the observed effect of PCs on the decomposition of H2O2 is indeed related to the assembly structure (vesicle vs micelles vs monomers) and is clearly not related to the presence of unsaturated hydrocarbon chains. Fluorescence polarization measurements of two fluorescent probes embedded either in the acyl chain region of the vesicles (DPH, 1,6-diphenyl-1,3,5-hexatriene) or on the surface of the vesicles (TMA-DPH, 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene iodide) show that the presence of H2O2 leads to a decrease in the fluidity of the lipid-water surface and not to a change in the fluidity of the hydrophobic region of the vesicle bilayer. This indicates that the decomposition of H2O2 is triggered through interactions between H2O2 and the polar head group area of PC vesicles.     

Heterodyne Interferometers Using Orthogonally Polarized and Two-Frequency Shifted Light Sources with Super-high Extinction Ratio

This paper describes heterodyne interferometers using orthogonally polarized and two-frequency shifted light sources of two types with super-high extinction ratio to reduce non-linearity of the interferometer due to polarization cross-talk. The acousto-optic modulators are used to shift light frequency. In the first interferometer the light source with Glan-Thomson prisms of very high extinction ratio (50 dB) is used to make the polarization cross-talk very small. In the second interferometer the light source of two-frequency shifted beams with small crossing angle (2.5 rnrad-10 mrad) is used to completely exclude non-linearity of the interferometer due to polarization cross-talk. By measuring the thickness of vacuum evaporation film, it was demonstrated that the interferometers are useful to measure thickness of a thin film in nanometer order.