CE coupling with end-column electrochemiluminescence detection for chiral separation of disopyramide

CE with electrochemiluminescence, (ECL) detection technique was successfully applied for the chiral separation of a kind of class IA antiarrhythmic racemic drug. To the best of our knowledge, this is the first report of ECL detection used in chiral CE. To get better detection sensitivity and good enantioresolution at the same time, the conditions of capillary inlet and outlet buffer were systematically optimized. Unlike the traditional chiral separation method, the buffers we used in the capillary inlet and outlet differed from each other in terms of buffer pH, ionic strength, type of BGE as well as buffer composition. Under the optimum conditions, baseline enantioseparation and highly sensitive detection of the enantiomers were achieved. Wide linear relationship of each enantiomer was achieved in the range of 5 x 10(-7) to 2 x 10(-5) mol/L with relative coefficients of 0.996 and 0.997, respectively. The detection limits were estimated to be 8 x 10(-8) and 1.0 X 10(-7) mol/L (S/N = 3) for the enantiomers, respectively. In addition, a successful application of this new method to the chiral separation of the racemic drug in spiked plasma samples confirmed the validity and applicability of the chiral CE-ECL method.

Design of Mono-symmetric LiteSteel Beam Floor Joists with Web Openings

The new cold-formed LiteSteel beam (LSB) sections have found increasing popularity in residential, industrial and commercial buildings due to their lightweight and cost-effectiveness. They have the beneficial characteristics of including torsionally rigid rectangular flanges combined with economical fabrication processes. Currently there is significant interest in using LSB sections as flexural members in floor joist systems. When used as floor joists, the LSB sections require holes in the web to provide access for inspection and various services. But there are no design methods that provide accurate predictions of the moment capacities of LSBs with web holes. In this study, the buckling and ultimate strength behaviour of LSB flexural members with web holes was investigated in detail by using a detailed parametric study based on finite element analyses with an aim to develop appropriate design rules and recommendations for the safe design of LSB floor joists. Moment capacity curves were obtained using finite element analyses including all the significant behavioural effects affecting their ultimate member capacity. The parametric study produced the required moment capacity curves of LSB section with a range of web hole combinations and spans. A suitable design method for predicting the ultimate moment capacity of LSB with web holes was finally developed. This paper presents the details of this investigation and the results

meso-Porphyrinylphosphine Oxides: Mono- and Bidentate Ligands for Supramolecular Chemistry and the Crystal Structures of Monomeric [10,20-Diphenylporphyrinatonickel(II)-5,15-diyl]-bis-[P(O)Ph2] and Polymeric Self-Coordinated ([10,20-Diphenylporphyrinatozinc(II)-5,15-diyl]-bis-[P(O)Ph2])

A series of porphyrins substituted in one or two meso-positions by diphenylphosphine oxide groups has been prepared by the palladium catalysed reaction of diphenylphosphine or its oxide with the corresponding bromoporphyrins. Compounds {MDPP-[P(O)Ph2]n} (M = H2, Ni, Zn; H2DPP = 5,15-diphenylporphyrin; n = 1, 2) were isolated in yields of 60-95%. The reaction is believed to proceed via the conventional oxidative addition, phosphination and reductive elimination steps, as the stoichiometric reaction of η1-palladio(II) porphyrin [PdBr(H2DPP)(dppe)] (H2DPP = 5,15-diphenylporphyrin; dppe = 1,2-bis(diphenylphosphino)ethane) with diphenylphosphine oxide also results in the desired mono-porphyrinylphosphine oxide [H2DPP-P(O)Ph2]. Attempts to isolate the tertiary phosphines failed due to their extreme air-sensitivity. Variable temperature 1H NMR studies of [H2DPP-P(O)Ph2] revealed an intrinsic lack of symmetry, while fluorescence spectroscopy showed that the phosphine oxide group does not behave as a "heavy atom" quencher. The electron withdrawing effect of the phosphine oxide group was confirmed by voltammetry. The ligands were characterised by multinuclear NMR and UV-visible spectroscopy as well as mass spectrometry. Single crystal X-ray crystallography showed that the bis(phosphine oxide) nickel(II) complex {[NiDPP-[P(O)Ph2]2} is monomeric in the solid state, with a ruffled porphyrin core and the two P=O fragments on the same side of the average plane of the molecule. On the other hand, the corresponding zinc(II) complex formed infinite chains through coordination of one Ph2PO substituent to the neighbouring zinc porphyrin through an almost linear P=O---Zn unit, leaving the other Ph2PO group facing into a parallel channel filled with disordered water molecules. These new phosphine oxides are attractive ligands for supramolecular porphyrin chemistry.

An infrared study of adsorption of paranitrophenol on mono, di and trialkyl surfactant intercalated organoclays

Infrared spectroscopy has been used to study the adsorption of paranitrophenol on mono, di and tri alkyl surfactant intercalated montmorillonite. Organoclays were obtained by the cationic exchange of mono, di and tri alkyl chain surfactants for sodium ions [hexadecyltrimethylammonium bromide (HDTMAB), dimethyldioctadecylammonium bromide (DDOAB), methyltrioctadecylammonium bromide (MTOAB)] in an aqueous solution with Na-montmorillonite. Upon formation of the organoclay, the properties change from strongly hydrophilic to strongly hydrophobic. This change in surface properties is observed by a decrease in intensity of the OH stretching vibrations assigned to water in the cation hydration sphere of the montmorillonite. As the cation is replaced by the surfactant molecules the paranitrophenol replaces the surfactant molecules in the clay interlayer. Bands attributed to CH stretching and bending vibrations change for the surfactant intercalated montmorillonite. Strong changes occur in the HCH deformation modes of the methyl groups of the surfactant. These changes are attributed to the methyl groups locking into the siloxane surface of the montmorillonite. Such a concept is supported by changes in the SiO stretching bands of the montmorillonite siloxane surface. This study demonstrates that paranitrophenol will penetrate into the untreated clay interlayer and replace the intercalated surfactant in surfactant modified clay, resulting in the change of the arrangement of the intercalated surfactant.

Advanced numerical characterization of mono-crystalline copper with defects

Based on the embedded atom method (EAM) and molecular dynamics (MD) method, the mono-crystalline copper with different defects is investigated through tension and nanoindentation simulation. The single-crystal copper nanowire with surface defects is firstly studied through tension. For validation, the tension simulations for nanowire without defect are carried out under different temperatures and strain rates. The defects on nanowires are then systematically studied in considering different defects orientation distribution. It is found that the Young’s modulus is insensitive of surface defects and centro-plane defects. However, the yield strength and yield point show a significant decrease due to the different defects. Specially, the 〖45〗^° defect in surface and in (200) plane exerts the biggest influence to the yield strength, about 34.20% and 51.45% decrease are observed, respectively. Different defects are observed to serve as a dislocation source and different necking positions of the nanowires during tension are found. During nanoindentation simulation, dislocation is found nucleating below the contact area, but no obvious dislocation is generated around the nano-cavity. Comparing with the perfect substrate during nanoindentation, the substrate with nano-cavities emerged less dislocations, it is supposed that the nano-cavity absorbed part of the indent energy, and less plastic deformation happened in the defected substrate.

A Raman spectroscopic study of the mono-hydrogen phosphate mineral dorfmanite Na2(PO3OH)•2H2O – and in comparison with brushite

Aspects of the molecular structure of the mineral dorfmanite Na2(PO3OH)•2H2O were determined by Raman spectroscopy. The mineral originated from the Kedykverpakhk Mt., Lovozero, Kola Peninsula, Russia. Raman bands are assigned to the hydrogen phosphate units. The intense Raman band at 949 cm-1 and the less intense band at 866 cm-1 are assigned to the PO3 and POH stretching vibrations. Bands at 991, 1066 and 1141 cm-1 are assigned to the ν3 antisymmetric stretching modes. Raman bands at 393, 413 and 448 cm-1 and 514, 541 and 570 cm-1 are attributed to the ν2 and ν4 bending modes of the HPO4 units, respectively. Raman bands at 3373, 3443 and 3492 cm-1 are assigned to water stretching vibrations. POH stretching vibrations are identified by bands at 2904, 3080 and 3134 cm-1. Raman spectroscopy has proven very useful for the study of the structure of the mineral dorfmanite.

Plastic bending behaviour and section moment capacities of mono-symmetric LiteSteel Beams with web openings

Recently developed cold-formed LiteSteel beam (LSB) sections have found increasing popularity in residential, industrial and commercial buildings due to their light weight and cost-effectiveness. Currently, there is significant interest in the use of LSB sections as flexural members in floor joist systems, although they can be used as flexural and compression members in a range of building systems. The plastic bending behaviour and section moment capacity of LSB sections with web holes can be assumed to differ from those without, but have yet to be investigated. Hence, no appropriate design rules for determining the section moment capacity of LSB sections with web holes are yet available. This paper presents the results of an investigation of the plastic bending behaviour and section moment capacity of LSB sections with circular web holes. LSB sections with varying circular hole diameters and degrees of spacing were considered. The paper also describes the simplified finite element (FE) modelling technique employed in this study, which incorporates all of the significant behavioural effects that influence the plastic bending behaviour and section moment capacity of these sections. The numerical and experimental test results and associated findings are also presented.

Numerical method for predicting the elastic lateral distortional buckling moment of a mono-symmetric beam with web openings

When used as floor joists, the new mono-symmetric LiteSteel beam (LSB) sections require web openings to provide access for inspections and various services. The LSBs consist of two rectangular hollow flanges connected by a slender web, and are subjected to lateral distortional buckling effects in the intermediate span range. Their member capacity design formulae developed to date are based on their elastic lateral buckling moments, and only limited research has been undertaken to predict the elastic lateral buckling moments of LSBs with web openings. This paper addresses this research gap by reporting the development of web opening modelling techniques based on an equivalent reduced web thickness concept and a numerical method for predicting the elastic buckling moments of LSBs with circular web openings. The proposed numerical method was based on a formulation of the total potential energy of LSBs with circular web openings. The accuracy of the proposed method’s use with the aforementioned modelling techniques was verified through comparison of its results with those of finite strip and finite element analyses of various LSBs.

Member moment capacities of mono-symmetric LiteSteel beam floor joists with web openings

Recently developed cold-formed LiteSteel beam (LSB) sections have found increasing popularity in residential, industrial and commercial buildings due to their light weight and cost-effectiveness. Another beneficial characteristic is that they allow torsionally rigid rectangular flanges to be combined with economical fabrication processes. Currently, there is significant interest in the use of LSB sections as flexural members in floor joist systems. When used as floor joists, these sections require openings in the web to provide access for inspection and other services. At present, however, there is no design method available that provides accurate predictions of the moment capacities of LSBs with web openings. This paper presents the results of an investigation of the buckling and ultimate strength behaviour of LSB flexural members with web openings. A detailed fine element analysis (FEA)-based parametric study was conducted with the aim of developing appropriate design rules and making recommendations for the safe design of LSB floor joists. The results include the required moment capacity curves for LSB sections with a range of web opening combinations and spans and the development of appropriate design rules for the prediction of the ultimate moment capacities of LSBs with web openings.

Binding of small mono- and oligomeric integrin ligands to membrane-embedded integrins monitored by surface plasmon-enhanced fluorescence spectroscopy

We recently developed a binding assay format by incorporating native transmembrane receptors into artificial phospholipid bilayers on biosensor devices for surface plasmon resonance spectroscopy. By extending the method to surface plasmon-enhanced fluorescence spectroscopy (SPFS), sensitive recording of the association of even very small ligands is enabled. Herewith, we monitored binding of synthetic mono- and oligomeric RGD-based peptides and peptidomimetics to integrins alphavbeta3 and alphavbeta5, after having confirmed correct orientation and functionality of membrane-embedded integrins. We evaluated integrin binding of RGD multimers linked together via aminohexanoic acid (Ahx) spacers and showed that the dimer revealed higher binding activity than the tetramer, followed by the RGD monomers. The peptidomimetic was also found to be highly active with a slightly higher selectivity toward alphavbeta3. The different compounds were also evaluated in in vitro cell adhesion tests for their capacity to interfere with alphavbeta3-mediated cell attachment to vitronectin. We hereby demonstrated that the different RGD monomers were similarly effective; the RGD dimer and tetramer showed comparable IC50 values, which were, however, significantly higher than those of the monomers. Best cell detachment from vitronectin was achieved by the peptidomimetic. The novel SPFS-binding assay platform proves to be a suitable, reliable, and sensitive method to monitor the binding capacity of small ligands to native transmembrane receptors, here demonstrated for integrins.

Mechanisms of mono- and poly-ubiquitination : ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine

Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/ E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.