Aerobic catechol oxidation catalyzed by a bis(mu-oxo)dimanganese(III,III) complex via a manganese(II)-semiquinonate complex

A 3,5-di-tert-butyl-1,2-semiquinonato (DTBSQ) adduct of Mn(II) was prepared by a reaction between Mn(II)(TPA)Cl(2) (TPA = tris(pyridin-2-ylmethyl)amine) and DTBSQ anion and was isolated as a tetraphenylborate salt. The X-ray crystal structure revealed that the complex is formulated as a manganese(II)-semiquinonate complex [Mn(II)(TPA)(DTBSQ)](+) (1). The electronic spectra in solution also indicated the semiquinonate coordination to Mn. The exposure of 1 in acetonitrile to dioxygen afforded 3,5-di-tert-butyl-1,2-benzoquione and a bis(mu-oxo)dimanganese(III,III) complex [Mn(III)(2)(mu-oxo)(2)(TPA)(2)](2+) (2). The reaction of 2 with 3,5-di-tert-butylcatechol (DTBCH(2)) quantitatively afforded two equivalents of 1 under anaerobic conditions. The highly efficient catalytic oxidation of DTBCH(2) with dioxygen was achieved by combining the above two reactions, that is, by constructing a catalytic cycle involving both manganese complexes 1 and 2. It was revealed that dioxygen is reduced to water but not to hydrogen peroxide in the catalytic cycle.     

Rapid,simple, and highly sensitive analysis of drugs in biological samples using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry

Rapid and precise identification of toxic substances is necessary for urgent diagnosis and treatment of poisoning cases and for establishing the cause of death in postmortem examinations. However, identification of compounds in biological samples using gas chromatography and liquid chromatography coupled with mass spectrometry entails time-consuming and labor-intensive sample preparations. In this study, we examined a simple preparation and highly sensitive analysis of drugs in biological samples such as urine, plasma, and organs using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry (TLC/MALDI/MS). When the urine containing 3,4-methylenedioxymethamphetamine (MDMA) without sample dilution was spotted on a thin-layer chromatography (TLC) plate and was analyzed by TLC/MALDI/MS, the detection limit of the MDMA spot was 0.05 ng/spot. The value was the same as that in aqueous solution spotted on a stainless steel plate. All the 11 psychotropic compounds tested (MDMA, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, methamphetamine, p-hydroxymethamphetamine, amphetamine, ketamine, caffeine, chlorpromazine, triazolam, and morphine) on a TLC plate were detected at levels of 0.05 − 5 ng, and the type (layer thickness and fluorescence) of TLC plate did not affect detection sensitivity. In addition, when rat liver homogenate obtained after MDMA administration (10 mg/kg) was spotted on a TLC plate, MDMA and its main metabolites were identified using TLC/MALDI/MS, and the spots on a TLC plate were visualized by MALDI/imaging MS. The total analytical time from spotting of intact biological samples to the output of analytical results was within 30 min. TLC/MALDI/MS enabled rapid, simple, and highly sensitive analysis of drugs from intact biological samples and crude extracts. Accordingly, this method could be applied to rapid drug screening and precise identification of toxic substances in poisoning cases and postmortem examinations.     

Replica theory of the rigidity of structural glasses

We present a first principle scheme to compute the rigidity, i.e., the shear-modulus of structural glasses at finite temperatures using the cloned liquid theory, which combines the replica theory and the liquid theory. With the aid of the replica method which enables disentanglement of thermal fluctuations in liquids into intra-state and inter-state fluctuations, we extract the rigidity of metastable amorphous solid states in the supercooled liquid and glass phases. The result can be understood intuitively without replicas. As a test case, we apply the scheme to the supercooled and glassy state of a binary mixture of soft-spheres. The result compares well with the shear-modulus obtained by a previous molecular dynamic simulation. The rigidity of metastable states is significantly reduced with respect to the instantaneous rigidity, namely, the Born term, due to non-affine responses caused by displacements of particles inside cages at all temperatures down to T = 0. It becomes nearly independent of temperature below the Kauzmann temperature T(K). At higher temperatures in the supercooled liquid state, the non-affine correction to the rigidity becomes stronger suggesting melting of the metastable solid state. Inter-state part of the static response implies jerky, intermittent stress-strain curves with static analogue of yielding at mesoscopic scales.     

Effects of Holdfast of Laminaria japonica on Listeria Invasion on Enterocyte-Like Caco-2 Cells and NO Production of Macrophage RAW 264.7 Cells

Listeria monocytogenes (Lm) causes food poisoning in humans mainly through consumption of ready-to-eat foods. Immunocompromised persons are at the highest risk for infection. We investigated effects of crude soluble polysaccharides (SPS) and ethanolic extract (EE) fractions of frond (kombu) and holdfast (ganiashi) parts of Laminaria japonica on Lm invasion into human enterocyte-like Caco-2 cells and immune and/or inflammatory reactions of murine macrophage RAW 264.7 cells. Recovery and viscosity were high in kombu SPS. Total phenolic content and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity and Fe-reducing power) were higher in ganiashi EE. EE of ganiashi, rather than kombu, suppressed the Lm invasion into the differentiated Caco-2 cells, though the inhibitory effect of SPS was not significant. Ganiashi SPS increased the nitric oxide (NO) production of intact RAW 264.7 cells. On the other hand, the NO production from Escherichia coli O111 lipopolysaccharide-activated cells was suppressed by kombu SPS and ganiashi EE. These results suggest that L. japonica, particularly ganiashi, might suppress the invasion and infection of Lm and also the inflammation.     

Diastereoselective protonation on radical anions of electron-deficient alkenes via photoinduced electron transfer

Diastereoselective protonations in the photoinduced electron transfer (PET) reactions of 1,1-dicyanoethene derivatives (1a-e) by use of organosilicon compounds such as allyltrimethylsilane (2) and benzyltrimethylsilane (5) are described. Irradiation of an acetonitrile-acetic acid solution containing 4-tert-butylcyclohexylidenepropanedinitrile (1a) and an excess of 2 in the presence of phenanthrene (Phen) as a sensitizer afforded reduction and allylated products (3a, 4a) in 63:37 and 57:43 ratios in a less regioselective manner. Photoreactions of 3,3,5-trimethylcyclohexylidenepropanedinitrile (1b), 2-methylcyclohexylidenepropanedinitrile (1c), bicyclo[2.2.1]-2-heptylidenepropanedinitrile (1d), and 1,7,7-trimethylbicyclo[2.2.1]-2-heptylidenepropanedinitrile (1e) with 2 showed higher diastereoselectivity via the PET process. Similar diastereoselectivities were obtained in the Phen-sensitized photoreaction of 1a-e with 5. When 2,4,6-trimethylpyridinium tosylate (7) was used as a proton source in place of acetic acid, the product ratios were substantially changed in several cases. From these results, steric and torsional effects have been postulated as important factors for the control of the diastereoselectivity in these PET reactions.     

Synthesis and antifungal activity of novel 14-membered benzomacrolides, as galbonolide analogues

Asymmetric total synthesis of benzene analogues of galbonolide, a 14-membered antifungal macrolide, possessing a benzene ring instead of a conjugated diene structure, was achieved starting from chiral 1-aryl-1-propanol obtained by enzyme-catalyzed kinetic resolution with high enantioselectivity. Representatively, a method for the introduction of a methylthio and chloride function at the vinyl position was also established. The resulting analogues unfortunately exhibited very little antifungal potency in comparison with galbonolide A.     

Doppler-free two-photon excitation spectroscopy and the Zeeman effects. Perturbations in the 14(0)1 and 1(0)(1)14(0)1 bands of the S1 <-- S0 transition of C6D6

Doppler-free two-photon excitation spectra and the Zeeman effects for the 1 band of the S1 1B2u <-- S0 1A1g transition in gaseous benzene-d6 were measured. Although the spectral lines were strongly perturbed, almost all of the lines near the band origin could be assigned. From a deperturbation analysis, the perturbation near the band origin was identified as originating from an anharmonic resonance interaction. Perturbation centered at K = 28-29 in the 14(0)1 band was analyzed, and it was identified as originating from a perpendicular Coriolis interaction. The symmetry and the assignment of the perturbing state proposed by Schubert et al. (Schubert, U.; Riedle, E.; Neusser, H. J. J. Chem. Phys. 1989, 90, 5994.) were confirmed. No perturbation originating from an interaction with a triplet state was observed in both bands. From the Zeeman spectra and the analysis, it is demonstrated that rotationally resolved levels are not mixed with a triplet state. The intersystem mixing is not likely to occur at levels of low excess energy in the S1 state of an isolated benzene. Nonradiative decay of an isolated benzene in the low vibronic levels of the S1 state will occur through the internal mixing followed by the rotational and vibrational relaxation in the S0 state.     

A Comparison of Membrane Emulsification Obtained Using SPG (Shirasu Porous Glass) and PTFE [Poly(Tetrafluoroethylene)] Membranes

SPG (Shirasu porous glass) membrane emulsification used to prepare uniform polymeric microspheres is briefly reviewed, and the performance of a hydrophilically treated PTFE [poly(tetrafluoroethylerie)] membrane is described and compared with that of the SPG membrane. A mixture of styrene. divinyl benzene and hexadecane (HD) was extruded through the membranes and dispersed in an aqueous phase containing polyvinylalcohol (PVA) and sodium lauryl sulfate (SLS) as mixed stabilizers. A hvdrophilically treated PTFE membrane was used with a stainless steel mesh support so that the membrane would not expand to affect the pore size during the emulsification. The nominal pore size of the PTFE membrane was replaced with the calculated one using a theoretical expression derived from the force balance between the external pressure and the interfacial tension between oil and water phases. The emulsion droplets prepared with the PTFE membrane revealed a broader size distribution than those obtained with the SPG membrane, and the rate of emulsificaton was nearly same for both membranes. Droplet size control was readily possible. The performance was significantly affected by the adsorption behavior of the stabilizers on the membrane surfaces. The contact angle profile of oil droplets on the PTFE membrane implied that the hydrophilically treated PTFE membrane is still hydrophobic compared to the SPG membrane. This tendency was reflected by the dependence of the average droplet diameter (and coefficient of variation, CV) on the concentration and composition of mixed stabilizers.     

Synthesis of the side chain of a novel carbapenem via iodine-mediated oxidative cyclization of (1R)-N-(1-aryl-3-butenyl)acetamide

A (2R,4S)-trans-disubstituted pyrrolidine ring system was constructed by employing iodine-mediated oxidative cyclization of (1R)-N-[1-(4-bromophenyl)-3-butenyl]acetamide 3 as a key step. The resulting diastereomeric mixture of (2R)-2-aryl-4-acetoxypyrrolidine 4 was stereoselectively converted to the side-chain of a novel ultrabroad-spectrum carbapenem 1, via (2R,4R)-2-aryl-4-hydroxypyrrolidine 7.