Restoration of catalytic activity by the preservation of ligand structure: Cu-catalysed asymmetric conjugate addition with 1,1-diborylmethane

Reported herein is a novel reaction engineering protocol to enhance the efficiency of a transition metal-catalysed process by strategically preventing ligand degradation. Based on spectroscopic investigations, a decomposition pathway of a chiral phosphoramidite ligand during a Cu-catalysed reaction was identified. The involvement of the destructive process could be minimized under the modified reaction conditions that control the amount of nucleophilic alkoxide base, which is the origin of ligand decomposition. Overall, the strategy has been successfully applied to a new class of asymmetric conjugate addition reactions with bis[(pinacolato)boryl]methane, in which α,β-unsaturated enones are utilised as substrates.

A novel Cu-catalysed asymmetric conjugate addition reaction with bis[(pinacolato)boryl]methane using α,β-unsaturated enones as substrates has been developed on the basis of strategic preservation of the supporting ligand.     

Sensitive Determination of Felodipine in Human and Dog Plasma by Use of Liquid–Liquid Extraction and LC–ESI–MS–MS

Summary A sensitive and selective liquid chromatographic method coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) has been developed for quantification of felodipine in human and dog plasma. Compounds were separated on a 2.0 mm × 150 mm, 5.0 m particle, C₈ column with 1 m m ammonium acetate–acetonitrile, 20:80, pH 6.0, as mobile phase at a flow rate of 200 L min^–1. Nifedipine was used as internal standard. Plasma samples were extracted with diethyl ether, the centrifuged upper layer was evaporated, the residue was reconstituted with mobile phase, and the reconstituted samples were injected. The analytical column lasted for at least 1000 injections. By use of multiple reaction monitoring (MRM) mode in MS–MS felodipine and nifedipine were detected without severe interference from the human or dog plasma matrix. Felodipine produced a protonated precursor ion ([M + H]⁺) at m/z 384 and a corresponding product ion at m/z 338. And internal standard (nifedipine) produced a protonated precursor ion ([M + H]⁺) at m/z 347 and a corresponding product ion at m/z 315. Detection of felodipine in human and dog plasma was accurate and precise, with a limit of quantification of 0.05 ng mL^–1. The method has been successfully applied to preliminary pharmacokinetic study of felodipine in human and dog plasma.     

Complete 1H and 13C NMR spectral assignment of symmetric and asymmetric bis-spiropyran derivatives

(1)H and (13)C NMR spectra of symmetric and asymmetric bis-spiropyrans, Series 1-3, were completely assigned. Especially, the (1)H assignment of asymmetric spiropyrans was achieved by utilizing (1)H-(1)H COSY and nOe experiments. All of the carbons in the dye molecules were investigated through a combination of heteronuclear 2D-shift correlation spectroscopy (HETCOR), together with an attached proton test (APT).     

Lithium isotope separation by chemical exchange with polymer-bound azacrown compounds

The chromatographic separation of lithium isotopes was investigated by chemical exchange with the recently synthesized polymer-bound dibenzo pyridino diamide azacrown (DBPDA) and reduced dibenzo pyridino diamide azacrown (RDBPDA). Column chromatography was employed for the determination of the effect of solvents and ligand conformation on the separation coefficients. The maximum separation coefficients, , for the DBPDA and RDBPDA at 20.0±0.02°C with acetonitrile as eluent, were found to be 0.034±0.002 and 0.035±0.002, respectively. The isotope separation coefficient and adsorption capability of the lithium ion on the DBPDA and RDBPDA were only slightly dependent on ligand structure, but strongly dependent on the solvent. DBPDA and RDBPDA appeared to have almost the same value for the isotope separation coefficient of lithium.     

Issue Information

An integrated finite element method (FEM) is proposed to simulate incompressible two‐phase flows with surface tension effects, and three different surface tension models are applied to the FEM to investigate spurious currents and temporal stability. A Q2Q1 element is adopted to solve the continuity and Navier–Stokes equations and a Q2‐iso‐Q1 to solve the level set equation. The integrated FEM solves pressure and velocity simultaneously in a strongly coupled manner; the level set function is reinitialized by adopting a direct approach using interfacial geometry information instead of solving a conventional hyperbolic‐type equation. In addition, a consistent continuum surface force (consistent CSF) model is utilized by employing the same basis function for both surface tension and pressure variables to damp out spurious currents and to estimate the accurate pressure distribution. The model is further represented as a semi‐implicit manner to improve temporal stability with an increased time step. In order to verify the accuracy and robustness of the code, the present method is applied to a few benchmark problems of the static bubble and rising bubble with large density and viscosity ratios. The Q2Q1‐integrated FEM coupled with the semi‐implicit consistent CSF demonstrates the significantly reduced spurious currents and improved temporal stability. The numerical results are in good qualitative and quantitative agreements with those of the existing studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Structural and functional stabilities of artificially designed DNA ultra-thin films grown by silica Assistance

We report the structural and functional stabilities of artificially synthesized DNA ultra-thin films. Fully covered DNA ultra-thin films on a silica substrate were fabricated by the silica-assisted growth method and those samples were then incubated in various chemicals and physical conditions. The DNA ultra-thin films showed high maintainability under those harsh conditions and these results would aid to facilitate the use of artificial DNA ultra-thin films in advanced research areas such as biophotonics and bioelectronics.     

One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles from isoselenocyanates: unexpected formation of N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas

1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoselenocyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H-tetrazoles but also to interesting side products, namely N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the reactions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H-tetrazoles in good yields. This simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-thiotetrazole moiety in biomedical applications.     

Analysis of cell gap-dependent driving voltage in a fringe field-driven homogeneously aligned nematic liquid crystal display

We have studied cell gap-dependent driving voltage characteristics in a homogeneously aligned nematic liquid crystal (LC) cell driven by a fringe electric field, termed the fringe field switching (FFS) mode. The results show that for the FFS mode using a LC with positive dielectric anisotropy, the operating voltage decreases as the cell gap decreases, whereas it increases with a decreasing cell gap when using a LC with negative dielectric anisotropy. The difference between LCs is explained by simulation and experiment.     

Isolation of an Organic Solvent-Tolerant Lipolytic Enzyme from Uncultivated Microorganism

Although the use of lipases as biocatalysts has frequently been proposed, it is yet scarcely being implemented in industrial processes. This is mainly due to the difficulties associated with the discovery and engineering of new enzymes and the lack of versatile screening methods. In this study, we screened the available strategy from a metagenomic pool for the organic solvent-tolerant lipase with enhanced performance for industrial processes. A novel lipase was identified through functional screening from a metagenomic library of activated sludge in an Escherichia coli system. The gene encoding the lipase from the metagenomic pool, metalip1, was sequenced and cloned by PCR. Metalip1 encoding a polypeptide of 316 amino acids had typical residues essential for lipase such as pentapeptide (GXSXGG) and catalytic triad sequences (Ser160, Asp260, and His291). The deduced amino acid sequence of metalip1 showed high similarity to a putative lipase from Pseudomonas sp. CL-61 (80 %, ABC25547). Metalip1 was expressed in E. coli BL21 (DE3) with a his-tag and purified using a Ni-NTA chelating column and characterized. This enzyme showed high expression level and solubility in the heterologous E. coli host. This enzyme was active over broad organic solvents. Among organic solvents examined, dimethyl formamide was the best organic solvent for metalip1. We showed that function-based strategy is an effective method for fishing out an organic solvent-tolerant lipase from the metagenomic library. Also, it revealed high catalytic turnover rates, which make them a very interesting candidate for industrial application.