Preserving the chromatographic integrity of high-speed supercritical fluid chromatography separations using time-of-flight mass spectrometry

The advantage of high-speed time-of-flight-mass spectrometry (TOF-MS) detection for ultrafast qualitative supercritical fluid chromatography/mass spectrometry (SFC/MS) applications allows the superior resolving power of SFC to be exploited in high-throughput analysis. A chromatographic comparison of quadrupole MS and TOF-MS shows high-speed TOF total ion current data point sampling to be more indicative of fast SFC separations and corresponding short (1-2 s) baseline peak widths. Results shown for analysis of a six-compound mixture with two peaks eluting at 0.86 and 0.89 min exhibit >50% resolution by high-speed TOF data sampling, whereas the same peaks appear to coelute using quadrupole MS data sampling. Additionally, a marked improvement in the peak baseline widths is afforded by fast TOF data acquisition of 0.1 s/spectrum, resulting in a reduction in the baseline width, 1.6 s, of sulfanilamide in a four-compound mixture that is more than 2-fold greater than that achieved at the slower data acquisition of 0.5 s/spectrum. The resulting increase in resolution and improved peak shapes allow automatic integration routines to perform more effectively. For most classes of compounds amenable to high performance liquid chromatography, including druglike species, steroids, and polymers, the union of SFC with TOF-MS provides the maximum density of chemical information per unit time available with any high-speed chromatographic/mass spectrometric method.     

A NOVEL ZWITTERIONIC SILANE COUPLING AGENT FOR NONTHROMBOGENIC BIOMATERIALS

A novel silane coupling agent bearing sulfobetaine group, N,N-diethyl-N-（3-sulfopropyl）-aminopropyl- trimethoxysilane （DESATS）, was first designed, synthesized and characterized. Its solution property was studied by means of dynamic light scattering. DESATS was successfully bonded onto the surface of the glass and proved by ESCA. Platelet adhesion assay in vitro indicated that the nonthrombogenicity of glass slide modified with DESATS is greatly improved.     

Synthesis,spectroscopy and thermal properties of the nickel(II), palladium(II) and copper(II) complexes of bis(aminoalkyl)-oxamides (=LH2) including the crystal structure of Cu2L(NO3)2

Summary The synthesis of the Ni^II, Pd^II and Cu^II complexes of N, N-bis(aminoalkyl)oxamides (LH₂) is described and structures are proposed on the basis of their physical and spectroscopic properties. With Ni^II and Pd^II only one complex is formed with general formula NiL or PdL, characterised by coordination through two deprotonated amide N-atoms and two terminal NH₂ groups. With Cu^II it proved possible to obtain three structurally different compounds, depending on the pH, with general formulae Cu(LH₂)X₂, Cu₂(L)X₂ and CuL in which X=Cl, Br or NO₃. The structure of [Cu₂(C₈O₂N₄H₁₆](NO₃)₂ was solved by means ofx-ray diffraction; Mr=451.33, monoclinic, space group P2₁/n, a=9.503(4), b=7.614(1), c=10.407(3) Å, =98.43(3)°, V=744.3(7)ų, Z=2, Dx=1.202 g cm^–3, =1.33 cm^–1, (MoK)=0.71073 Å, F(000)=520, room temperature, R=0.043, wR=0.047 for 1080 observed [I>-3(I)] not systematically absent reflections out of 1423 measurements and 137 variables. The compound has a conformational chair/boat disorder with 82% in the more stable chair form.     

Determination of polar organic compounds by potentiometry at an anodically pretreated nickel oxide electrode

The open-circuit potential drop of an oxidatively pretreated nickel electrode in 0.1 M NaOH was used to develop a technique for the determination of alcohols, amino acids, carbohydrates, etc., in aqueous solution. The electrode pretreatment consisted of the formation of nickel hydrated oxides on the electrode surface with an oxidation state > 2. Both electrochemical and chemical pre-oxidation of the electrode surface were examined. The analytical signal was the enhancement of the potential drop corresponding to analyte concentration. The analytical signal was linearly related to the logarithm of the analyte concentration. The limits of determination ranged from 1 mM for low-molecular-weight to 0.02 mM for alkyl polyether alcohols. The flow-injection technique allows convenient pretreatment and direct observation of the analytical signal. Interferences from chloride and calcium can be readily eliminated by excluding them during electrode pretreatment. Potentiometric measurements were correlated with amperometric anodic responses at the nickel oxide electrode, allowing an unusual direct comparison of the two methods.     

Interferences by transition metals and their elimination by cyanide as a complexing agent in the determination of arsenic using continuous flow HG-ICP-AES

The interfering effects of various foreign ions on the determination of arsenic were studied by hydride generation inductively coupled plasma atomic emission spectrometry (HG-ICP-AES). There were serious inhibiting interferences by Cu, Pb, Co, Au, Pd and Ni. However, by using cyanide as a complexing agent these interferences could be completely eliminated over a wide range of interferent concentration. The optimum chemical parameters for continuous arsine generation were studied. A major advantage of this technique is that it only needs low acid concentrations and produces less hazardous waste. Sensivity, selectivity and accuracy of the determination of arsenic by HG-ICP-AES were investigated. The detection limit (in 1 mol/l HCl medium) for arsenic(III) was 0.82 ng/ml. The relative standard deviation for ten determinations of a solution containing 50 ng/ml arsenic was 1.3%.     

Calcium oxalate monohydrate precipitation at membrane lipid rafts

The precipitation of calcium oxalate monohydrate (COM) was monitored at a Langmuir monolayer containing lipid raft domains. The raft-forming monolayer consists of a 2:1:1 mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/sphingomyelin/dihydrocholesterol, where the raft liquid ordered phase is enriched in sphingomyelin and the sterol. COM crystals, monitored by Brewster angle microscopy, appear at the phase boundary between the raft domains and the expanded phase.     

The use of semiempirical energy partitioning terms in the study of through space (homoaromatic) interactions

MNDO and AMI calculations, including configuration interactions, were performed on cycloheptatriene (2), 1,6-methano[10]annulene (3), and the tautomeric elassovalenes (4), (5), and (6). The goal of this study is to examine these systems and assess indicators of the importance of through space (homoaromatic) interactions. It is established that the two-center energy partitioning terms are capable of detecting favorable (negative two-center term) through space interactions. In cases of cyclic conjugation (homoconjugation), it is also shown that the inclusion of CI is necessary.     

Standard enthalpy of formation of lanthanum oxybritholites

Lanthanum-bearing silicate-oxyapatites or britholites, Ca_10–xLax(PO₄)_6–x(SiO₄)_xO with 1≤x≤6, have been synthesized by solid state reaction at high temperature. They were characterized by X-ray diffraction and IR spectroscopy. Using two microcalorimeters, the heat of solution of these compounds have been measured at 298 K in a solution of nitric and hydrofluoric acid. A strained least squares method was applied to the experimental results to obtain the solution enthalpies at infinite dilution, and the mixing enthalpy in two steps. In the first step the mixing enthalpy obtained is referenced to the britholite monosubstituted and to the oxysilicate. The mixing enthalpy referenced to the oxyapatite and to the oxysilicate is then extrapolated. In order to determine the enthalpies of formation of all the terms of the solution, thermochemical cycles were proposed and complementary experiments were performed. The results obtained show a decrease of the enthalpy of formation with the amount of Si and La introduced in the lattice. This was explained by the difference in the bond energies of (Ca–O, P–O) and (La–O, Si–O).     

Design and characterization of libraries of molecular fragments for use in NMR screening against protein targets

We have designed four generations of a low molecular weight fragment library for use in NMR-based screening against protein targets. The library initially contained 723 fragments which were selected manually from the Available Chemicals Directory. A series of in silico filters and property calculations were developed to automate the selection process, allowing a larger database of 1.79 M available compounds to be searched for a further 357 compounds that were added to the library. A kinase binding pharmacophore was then derived to select 174 kinase-focused fragments. Finally, an additional 61 fragments were selected to increase the number of different pharmacophores represented within the library. All of the fragments added to the library passed quality checks to ensure they were suitable for the screening protocol, with appropriate solubility, purity, chemical stability, and unambiguous NMR spectrum. The successive generations of libraries have been characterized through analysis of structural properties (molecular weight, lipophilicity, polar surface area, number of rotatable bonds, and hydrogen-bonding potential) and by analyzing their pharmacophoric complexity. These calculations have been used to compare the fragment libraries with a drug-like reference set of compounds and a set of molecules that bind to protein active sites. In addition, an analysis of the overall results of screening the library against the ATP binding site of two protein targets (HSP90 and CDK2) reveals different patterns of fragment binding, demonstrating that the approach can find selective compounds that discriminate between related binding sites.     

Synthesis, crystal structure, magnetic properties, and electronic structure of the new ternary vanadate CuMnVO4

A new magnetic oxide, CuMnVO4, was prepared, and its crystal structure was determined by single-crystal X-ray diffraction. The magnetic properties of CuMnVO4 were characterized by magnetic susceptibility and specific heat measurements, and the spin exchange interactions of CuMnVO4 were analyzed on the basis of spin-polarized electronic band structure calculations. CuMnVO4 contains MnO4 chains made up of edge-sharing MnO6 octahedra containing high-spin Mn2+ cations. Our work shows that CuMnVO4 undergoes a three-dimensional antiferromagnetic transition at approximately 20 K. Both the intrachain and interchain spin exchanges are antiferromagnetic, and the interchain spin exchange is not negligible compared to the intrachain spin exchange.