Measurement of the Lambda b0 lifetime in Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV

We report a measurement of the Lambda b0 lifetime in the exclusive decay Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV using an integrated luminosity of 1.0 fb-1 of data collected by the CDF II detector at the Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda b0)=1.593(-0.078)(+0.083)(stat)+/-0.033(syst) ps. This is the single most precise measurement of tau(Lambda b0) and is 3.2sigma higher than the current world average.     

Observation of exclusive electron-positron production in hadron-hadron collisions

We present the first observation of exclusive e(+)e(-) production in hadron-hadron collisions, using pp[over] collision data at (square root) s = 1.96 TeV taken by the run II Collider Detector at Fermilab, and corresponding to an integrated luminosity of 532 pb(-1). We require the absence of any particle signatures in the detector except for an electron and a positron candidate, each with transverse energy E(T) > 5 GeV and pseudorapidity |eta| < 2. With these criteria, 16 events are observed compared to a background expectation of 1.9+/-0.3 events. These events are consistent in cross section and properties with the QED process pp[over] --> p + e(+)e(-) + p[over] through two-photon exchange. The measured cross section is 1.6(-0.3)(+0.5)(stat) +/- 0.3(syst) pb. This agrees with the theoretical prediction of 1.71+/-0.01 pb.     

Asymmetric Total Synthesis of ent‐Pyripyropene A

An asymmetric total synthesis of ent‐pyripyropene A was achieved by a convergent synthetic route. We used our originally developed Ti^III‐catalyzed radical cyclization to construct an AB‐ring portion that consisted of a trans‐decalin skeleton with five contiguous stereogenic centers. The coupling between the AB‐ring and the DE‐ring portions, and a subsequent C‐ring cyclization, led to the total synthesis of ent‐pyripyropene A. An evaluation of the insecticidal activity of ent‐pyripyropene A against two aphid species revealed that ent‐pyripyropene A was 35–175 times less active than naturally occurring pyripyropene A. This result indicated that the biological target of pyripyropene A recognizes the absolute configuration of pyripyropene A.     

Atropisomerism observed in indometacin derivatives

To elucidate the active conformation of indometacin that differentiates between cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the stereochemistry around the N-benzoylated indole moiety of indometacin was studied. Resolution of stable atropisomers as representative conformations was found to be possible by restricting rotation about the N-C7' and/or C7'-C1' bond. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer.     

Oriented reconstitution of a membrane protein in a giant unilamellar vesicle: experimental verification with the potassium channel KcsA

We report a method for the successful reconstitution of the KcsA potassium channel with either an outside-out or inside-out orientation in giant unilamellar vesicles, using the droplet-transfer technique. The procedure is rather simple. First, we prepared water-in-oil droplets lined with a lipid monolayer. When solubilized KcsA was encapsulated in the droplet, it accumulated at monolayers of phosphatidylglycerol (PG) and phosphoethanolamine (PE) but not at a monolayer of phosphatidylcholine (PC). The droplet was then transferred through an oil/water interface having a preformed monolayer. The interface monolayer covered the droplet so as to generate a bilayer vesicle. By creating chemically different lipid monolayers at the droplet and oil/water interface, we obtained vesicles with asymmetric lipid compositions in the outer and inner leaflets. KcsA was spontaneously inserted into vesicles from the inside or outside, and this was accelerated in vesicles that contained PE or PG. Integrated insertion into the vesicle membrane and the KcsA orientation were examined by functional assay, exploiting the pH sensitivity of the opening of the KcsA when the pH-sensitive cytoplasmic domain (CPD) faces toward acidic media. KcsA loaded from the inside of the PG-containing vesicles becomes permeable only when the intravesicular pH is acidic, and the KcsA loaded from the outside becomes permeable when the extravesicular pH is acidic. Therefore, the internal or external insertion of KcsA leads to an outside-out or inside-out configuration so as to retain its hydrophilic CPD in the added aqueous side. The CPD-truncated KcsA exhibited a random orientation, supporting the idea that the CPD determines the orientation. Further application of the droplet-transfer method is promising for the reconstitution of other types of membrane proteins with a desired orientation into cell-sized vesicles with a targeted lipid composition of the outer and inner leaflets.     

A risk assessment of human ether-a-go-go-related gene potassium channel inhibition by using lipophilicity and basicity for drug discovery

The blockade of human ether-a-go-go-related gene (hERG) potassium channels is widely regarded as the predominant cause of drug-induced QT prolongation. The correlation analysis between the inhibition of the hERG channel (hERG inhibition) and physicochemical properties was investigated by use of in-house quinolone antibiotics as model compounds. In order to establish a simple prediction model of hERG inhibition, we focused on the comprehensible physicochemical parameters such as lipophilicity (log P) and basicity (pK(a)). At first, the risk associated with increasing log P and pK(a) was examined by statistical analysis. It was demonstrated that the risk associated with increasing log P and pK(a) by one unit, respectively, almost identically increased. Consequently, equal attention should be paid to both parameters on hERG inhibition. Next, a prediction model of hERG inhibition which was represented by log P and pK(a) was investigated. As a result, we built the stepwise discriminant prediction model which took advantage of the risk judgment by zone classification. In conclusion, the impact of log P and pK(a) on hERG inhibition was clarified relatively and quantitatively. The quantitative risk assessment established based on both parameters, was considered to be a practical and useful tool in avoiding hERG inhibition and in the rational drug design for drug discovery, especially in lead optimization. Moreover, we also carried out a trend analysis using a different derivative and demonstrated that both parameters were equally significant for hERG inhibition.     

A new C2-symmetric azolium compound for Cu-catalyzed asymmetric conjugate addition of R2Zn to cyclic enone

A new chiral N-heterocyclic carbene (NHC) ligand was designed. Thus, an efficient synthetic route to C₂-symmetric bis(hydroxyamide)-functionalized benzimidazolium salts from chiral β-amino alcohols was developed. The combination of Cu(OTf)₂ and the chiral azolium compound efficiently promoted the conjugate addition reaction of cyclic enone with dialkylzinc to give the corresponding adduct in good yield. Among a series of chiral NHC proligands, the functionalized benzimidazolium chloride possessing a tert-butyl group as a stereodirecting group was found to be the best choice of ligand. Under optimized reaction conditions, an excellent enantioselectivity (96% ee) was realized by allowing 2-cyclohepten-1-one to react with Bu₂Zn at room temperature.     

Stereochemistry of reduction of the C-24,25 double bond in the conversion of desmosterol into cholesterol

Feeding of the chemically prepared [24-¹³C, 24-²H]desmosterol to cell-free systems derived from rat liver and silkworm gut and to cultured cells of Oryza sativa followed by deuterium-decoupled ¹H, ¹³C shift correlation NMR analysis of the biosynthesized cholesterol revealed the stereospecific incorporation of hydrogen atoms from the re-face of the C-24 position of desmosterol.     

Near-infrared intersubband absorption in (CdS/ZnSe)/BeTe type-II super-lattices grown on GaAs substrate by MBE

We study the dependence of absorption wavelength on the well width in the (CdS/ZnSe)/BeTe super-lattices(SL). With well-width reduction, the wavelength decreases from 1.795 to 1.57 μm. Structural properties, strain state and interface composition are determined via XRD measurement. A (CdS/ZnSe)/Be_xMg_1−xTe structure is prepared and XRD reveals the average lattice constant match to GaAs substrate. TEM reveals that numerous stacking faults exist in the (CdS/ZnSe)/BeTe structure, and stacking faults are completely suppressed in (CdS/ZnSe)/Be_xMg_1−xTe SLs. Intersubband transition down to 1.535–1.55 μm have been observed in SLs.