A new synthetic method: Direct replacement of the nitro group by hydrogen or deuterium

The nitro group in tertiary or secondary aliphatic nitro compounds is replaced by hydrogen or deuterium on treatment with tributyltin hydride or tributyltin deuteride, respectively.     

Ultra-slow muon facility for advanced μSR studies

A concept, a construction and an account of commissioning experiments up to May 1993 are given for the recently completed ultra-slow positive muon facility at the pulsed muon facility of UT-MSL/KEK. The intense and ultra-slow ⁺ beam with an extremely small phase-space volume to be produced in this facility will open new muon sciences includingSR studies on material surfaces.     

Ultra-slow muon facility for surface HFI studies

A concept, a design, a construction and an account of commissioning experiments are given for the recently completed ultra-slow muon facility at the pulsed muon facility of UT-MSL/KEK. The intense (more than 10³/s) slow ⁺ beam with an extremely narrow phase-space volume (0.2 eV×(3 cm)²) to be produced in this facility will open a new muon science including surface physics and chemistry and fundamental atomic physics.Post-doctoral fellow of Swiss National Science Foundation.     

Recent developments on creation of artificial metalloenzymes

Organic synthesis using biocatalysts has been developed over many years and is still a prominent area of research. In this context, various hybrid biocatalysts composed of a synthetic metal complex catalyst and a protein scaffold (i.e. “artificial metalloenzymes”) have been constructed. One of the most recent research areas in biocatalysts-mediated synthesis is CC bond/cleavage, the most important type of reaction in organic chemistry. Some of the artificial enzymes were applied to in-cell reactions as well as in vitro systems. The effects of the structural fluctuation in biomacromolecules on their functions have also been realized. This review article includes recent research examples of artificial metalloenzymes used to CC bond formation/cleavage. As a perspective, we also focus on how we apply protein dynamics factor for the creation of new generation artificial metalloenzymes.     

Method for optical resolution of racemic homochlorcyclizine and comparison of optical isomers in antihistamine activity and pharmacokinetics.

A method was developed for semi-preparative scale enantioseparation of racemic homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on Chiralcel OD column. The best resolution was achieved using an eluent composed of n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ could be resolved completely in one run. The optical purity of the enantiomers were both greater than 99.9%. The studies of antihistamine activity on guinea pig ileum demonstrated that l-HCZ is significantly more potent than d- and racemic HCZ. The pharmacokinetics of d- and l-HCZ after oral administration to rats also differed. The successful resolution of racemic HCZ permits comparison of the pharmacokinetics and antihistamine activity of the enantiomers.     

Effect of lipid composition on phospholipase A2-catalyzed membrane leakage in immobilized liposomes: sensitization for polychlorinated biphenyls detection with antibody affinity column tandem with fluorescent liposome column

Phospholipase A(2) (PLA(2))-catalyzed membrane leakage can be detected by immobilized liposomes containing a self-quenching fluorescent dye, calcein, on an open column using off-line analysis with a fluorescent spectrophotometer. The calcein release was found to be affected by the pH value, incubation time, and liposome compositions. The fluorescent signal from the negatively charged liposomes hydrolyzed by PLA(2) was 5 times higher than that from neutral liposomes. We utilized this enzymatic reaction to amplify signal to detect polychlorinated biphenyls (PCBs). To achieve this goal, we conjugated an analogue of PCB, 3,4-dichloroaniline, to PLA(2). The competitive immunoreaction between the 3,4-dichloroaniline-PLA(2) conjugate and PCB samples on the anti-PCB antibody column caused the release of the bound PLA(2) conjugates in proportion to the PCB concentration. The released PLA(2) conjugates was then passed through the tandem fluorescent liposome column causing release of fluorescent dye from the liposomes. Therefore, the signal of immunocompetitive assay was amplified on the fluorescent liposome column. The tandem column system achieves a high sensitivity by detecting the PCB concentration as low as 0.5 ng/mL in less than 20 min. It has great potential in detecting other pollutants, and has been used for sensitive immunoassays.     

Dioxo-molybdenum(VI) and mono-oxo-molybdenum(IV) complexes supported by new aliphatic dithiolene ligands: new models with weakened Mo=O bond characters for the arsenite oxidase active site

The cis-dioxo-molybdenum(VI) complexes, [MoO2(L(H))2]2- (1b), [MoO2(L(S))(2)]2- (2b), and [MoO2(L(O))2]2- (3b) (L(H) = cyclohexene-1,2-dithiolate, L(S) = 2,3-dihydro-2H-thiopyran-4,5-dithiolate, and L(O) = 2,3-dihydro-2H-pyran-4,5-dithiolate), with new aliphatic dithiolene ligands were prepared and investigated by infrared (IR) and UV-vis spectroscopic and electrochemical methods. The mono-oxo-molybdenum(IV) complexes, [MoO(L(H))2]2- (1a), [MoO(L(S))2]2- (2a), and [MoO(L(O))2]2- (3a), were further characterized by X-ray crystal structural determinations. The IR and resonance Raman spectroscopic studies suggested that these cis-dioxo molybdenum(VI) complexes (1b-3b) had weaker Mo=O bonds than the common Mo(VI)O2 complexes. Complexes 1b-3b also exhibited strong absorption bands in the visible regions assigned as charge-transfer bands from the dithiolene ligands to the cis-MoO2 cores. Because the oxygen atoms of the cis-Mo(VI)O2 cores are relatively nucleophilic, these complexes were unstable in protic solvents and protonation might occur to produce Mo(VI)O(OH), as observed with the oxidized state of arsenite oxidase.     

Isolation of heptadepsin, a novel bacterial cyclic depsipeptide that inhibits lipopolysaccharide activity

Lipopolysaccharide (LPS) is considered to cause various inflammatory reactions. We searched among microbial secondary metabolites for compounds that could inhibit LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and human myelocytic cell line HL-60 cells. In the course of our screening, we isolated a novel cyclic depsipeptide, which we named heptadepsin, from the whole culture broth of Paenibacillus sp. The addition of heptadepsin prior to LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any cytotoxicity. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS, but it did not inhibit TNF-alpha or IL-1beta-induced cell adhesion. The result of surface plasmon resonance (SPR) analysis revealed that heptadepsin interacted with lipid A directly. Thus, heptadepsin, a novel naturally occurring cyclic heptadepsipeptide, was shown to inactivate LPS by direct interaction with LPS.