Determination of boron in titanium alloys by means of ion exchange

There is need for a rapid method for the determination of moderate amounts of boron in titanium alloys. In this paper a method is proposed which uses ion exchange. The method is applicable to titanium alloys containing 0.025 to 1 per cent. boron. One or two grams of the sample are dissolved in hydrochloric acid, and the titanium and boron are oxidized with nitric acid. The bulk of the titanium is removed by a cation exchanger. A calcium carbonate separation is made to remove the residual titanium and adjust the acidity. The boron is then titrated with sodium hydroxide, after the addition of mannitol. None of the elements found in commercial titanium alloys interferes with the method.     

Reactions of the trimethylsilyl ion with 1,2-cyclopentanediol isomers in the collision region of a triple quadrupole instrument

Ion-molecule reactions with the trimethylsilyl ion were used to distinguish between cis- and trans-1,2-cyclopentanediol isomers. The ion kinetic energy of [Si(CH₃)₃]⁺ was varied from 0 eV to 15 eV (center of mass frame of reference). At low ion kinetic energies (<4 eV), there are significant differences in the relative stabilities and decomposition behavior of the adduct ions [M + Si(CH₃)₃]⁺. The cis-1,2-cyclopentanediol isomer favors decomposition of [M + Si(CH₃)₃]⁺ to yield the hydrated trimethylsilyl ion [Si(CH₃)₃OH₂]⁺ at m/z 91. For the trans isomer, the formation of the hydrated trimethylsilyl ion is an endothermic process with a definite threshold ion kinetic energy.     

Toward understanding the ionization of biomarkers from micrometer particles by bio-aerosol mass spectrometry

The appearance of informative signals in the mass spectra of laser-ablated bio-aerosol particles depends on the effective ionization probabilities (EIP) of individual components during the laser ionization process. This study investigates how bio-aerosol chemical composition governs the EIP values of specific components and the overall features of the spectra from the bio-aerosol mass spectrometry (BAMS). EIP values were determined for a series of amino acid, dipicolinic acid, and peptide aerosol particles to determine what chemical features aid in ionization. The spectra of individual amino acids and dipicolinic acid, as well as mixtures, were examined for extent of fragmentation and the presence of molecular ion dimers, which are indicative of ionization conditions. Standard mixtures yielded information with respect to the significance of secondary ion plume reactions on observed spectra. A greater understanding of how these parameters affect EIP and spectra characteristics of bio-aerosols will aid in the intelligent selection of viable future biomarkers for the identification of bio-terrorism agents.     

Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics

Asparagine glycosylation is one of the most common and important post-translational modifications of proteins in eukaryotic cells. N-glycosylation occurs when a triantennary glycan precursor is transferred en bloc to a nascent polypeptide (harboring the N-X-T/S sequon) as the peptide is cotranslationally translocated into the endoplasmic reticulum (ER). In addition to facilitating binding interactions with components of the ER proteostasis network, N-glycans can also have intrinsic effects on protein folding by directly altering the folding energy landscape. Previous work from our laboratories (Hanson et al. Proc. Natl. Acad. Sci. U.S.A. 2009, 109, 3131-3136; Shental-Bechor, D.; Levy, Y. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 8256-8261) suggested that the three sugar residues closest to the protein are sufficient for accelerating protein folding and stabilizing the resulting structure in vitro; even a monosaccharide can have a dramatic effect. The highly conserved nature of these three proximal sugars in N-glycans led us to speculate that introducing an N-glycosylation site into a protein that is not normally glycosylated would stabilize the protein and increase its folding rate in a manner that does not depend on the presence of specific stabilizing protein-saccharide interactions. Here, we test this hypothesis experimentally and computationally by incorporating an N-linked GlcNAc residue at various positions within the Pin WW domain, a small β-sheet-rich protein. The results show that an increased folding rate and enhanced thermodynamic stability are not general, context-independent consequences of N-glycosylation. Comparison between computational predictions and experimental observations suggests that generic glycan-based excluded volume effects are responsible for the destabilizing effect of glycosylation at highly structured positions. However, this reasoning does not adequately explain the observed destabilizing effect of glycosylation within flexible loops. Our data are consistent with the hypothesis that specific, evolved protein-glycan contacts must also play an important role in mediating the beneficial energetic effects on protein folding that glycosylation can confer.     

Unusual reactivity of bicyclo[2.2.1]heptene derivatives during the ozonolysis. Part 2

The ozonation of four bornene derivatives, prepared from (R)-(+)-pulegone, which possess a particularly hindered double bond, led to the formation of unexpected products depending on the nature of the solvent. The formation of the corresponding epoxides, ketones with the same skeleton, various lactones and even an allyl alcohol and an allyl chloride (allylic functionalisation) was observed. In two cases, products presenting a pulegone modified skeleton resulting from a Wagner-Meerwein rearrangement were obtained. The structure of three products was confirmed by crystallographic X-ray analysis. Mechanisms taking into account the rigid and congested structure of the reactants explain these results. The most striking steps were backed up by theoretical calculations.     

A concise and convergent synthesis of PA-824

An efficient four-step synthesis of PA-824, a promising antituberculosis drug candidate, has been developed. This concise approach offers significant improvements over the synthetic route currently used for large-scale production.     

Quantification of midazolam,morphine and metabolites in plasma using 96‐well solid‐phase extraction and ultra‐performance liquid chromatography–tandem mass spectrometry

Currently, pharmacokinetic–pharmacodynamic studies of sedatives and analgesics are performed in neonates and children to find suitable dose regimens. As a result, sensitive assays using only small volumes of blood are necessary to determine drug and metabolite concentrations. We developed an ultra‐performance liquid chromatographic method with tandem mass spectrometry detection for quantification of midazolam, 1‐hydroxymidazolam, hydroxymidazolamglucuronide, morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in 100 μL of plasma. Cleanup consisted of 96 wells micro‐solid phase extraction, before reversed‐phase chromatographic separation (ultra‐performance liquid chromatography) and selective detection using electrospray ionization tandem mass spectrometry. Separate solid‐phase extraction methods were necessary to quantify morphine, midazolam and their metabolites because of each group's physicochemical properties. Standard curves were linear over a large dynamic range with adequate limits of quantitation. Intra‐ and interrun accuracy and precision were within 85–115% (of nominal concentration using a fresh calibration curve) and 15% (coefficient of variation, CV) respectively. Recoveries were >80% for all analytes, with interbatch CVs (as a measure of matrix effects) of less than 15% over six batches of plasma. Stability in plasma and extracts was sufficient, allowing large autosampler loads. Runtime was 3.00 min per sample for each method. The combination of 96‐well micro‐SPE and UPLC‐MS/MS allows reliable quantification of morphine, midazolam and their major metabolites in 100 μL of plasma. Copyright © 2010 John Wiley & Sons, Ltd.     

Wagner-Meerwein rearrangement in the course of the ozonolysis of a bornene derivative

The ozonolysis of the bicyclo[2.2.1]heptene derivative 1 or 2 gave the octaline derivative 6 (the structure was confirmed by X-ray crystallographic analysis) or 7. The exo-addition of ozone to the double bond of 1 or 2 was followed by the fragmentation in carbonyl oxide and aldehyde. Then, the strong electrophilic character of the carbonyl oxide induces an unexpected Wagner-Meerwein rearrangement to give zwitterion 4. Finally, a fragmentation reaction with elimination of dioxygen gave the tetrasubstituted C-C double bonds of 6 or 7.     

Effect of the acyl group and the dodecylsulfonate chain on the inclusion of pyrene inside the cavity of β-cyclodextrin

The solubilization of pyrene in aqueous solution of β-cyclodextrin (β-CD) or its derivatives such as β-CD-hexanoyl, β-CD-benzoyl and β-CD-dodecylsulfonate was investigated by spectrophotometry. Linear and non-linear regression methods were used to estimate the association constants (K₁). A 1:1 stoichiometric ratio and different effects of the hexanoyl, benzoyl and dodecylsulfonate groups on the association constant were observed for the binary inclusion complex between pyrene and β-CD. The formation constant was shown to decrease when β-CD was modified by a dodecylsulfonate chain. The value of K₁ was 190 ± 10 L mol⁻¹ for the [pyrene/β-CD] complex and 145 L mol⁻¹ for the [pyrene/β-CD-dodecylsulfonate] complex. Partitioning of the pyrene molecules between the dodecylsulfonate chains and cyclodextrin cavities can explain the decrease in the association constant value. In the cases of β-CD-hexanoyl and β-CD-benzoyl derivatives, no association constants were detected. Results suggest that the high hydrophobicity of the hexanoyl and benzoyl groups prevents the inclusion of pyrene molecules inside the cyclodextrin cavity.