Oxygen isotope analysis of carbonates in the calcite-dolomite-magnesite solid-solution by high-temperature pyrolysis: initial results

Accurate and efficient measurement of the oxygen isotope composition of carbonates (delta(C) (18)O) based on the mass spectrometric analysis of CO(2) produced by reacting carbonate samples with H(3)PO(4) is compromised by: (1) uncertainties associated with fractionation factors (alpha(CO)(2)C) used to correct measured oxygen isotope values of CO(2)(delta(CO(2)(18)O) to delta(C) (18)O; and (2) the slow reaction rates of many carbonates of geological and environmental interest with H(3)PO(4). In contrast, determination of delta(C) (18)O from analysis of CO produced by high-temperature (>1400 degrees C) pyrolytic reduction, using an elemental analyser coupled to continuous-flow isotope-ratio mass spectrometry (TC/EA CF-IRMS), offers a potentially efficient alternative that measures the isotopic composition of total carbonate oxygen and should, therefore, theoretically be free of fractionation effects. The utility of the TC/EA CF-IRMS technique was tested by analysis of carbonates in the calcite-dolomite-magnesite solid-solution and comparing the results with delta(C) (18)O measured by conventional thermal decomposition/fluorination (TDF) on the same materials. Initial results show that CO yields are dependent on both the chemical composition of the carbonate and the specific pyrolysis conditions. Low gas yields (<100% of predicted yield) are associated with positive (>+0.2 per thousand) deviations in delta(C(TC/EA) (18)O compared with delta(C(TDF) (18)O. At a pyrolysis temperature of 1420 degrees C the difference between delta(C) (18)O measured by TC/EA CF-IRMS and TDF (Delta(C(TC/EA,TDF) (18)O) was found to be negatively correlated with gas yield (r = -0.785) and this suggests that delta(C) (18)O values (with an estimated combined standard uncertainty of +/-0.38 per thousand) could be derived by applying a yield-dependent correction. Increasing the pyrolysis temperature to 1500 degrees C also resulted in a statistically significant correlation with gas yield (r = -0.601), indicating that delta(C) (18)O values (with an estimated uncertainty of +/-0.43 per thousand) could again be corrected using a yield-dependent procedure. Despite significant uncertainty associated with TC/EA CF-IRMS analysis, the magnitude of the uncertainty is similar to that associated with the application of poorly defined values of alpha(CO)(2), (C) used to derive delta(C) (18)O from delta(CO(2) (18)O measured by the H(3)PO(4) method for most common carbonate phases. Consequently, TC/EA CF-IRMS could provide a rapid alternative for the analysis of these phases without any effective deterioration in relative accuracy, while analytical precision could be improved by increasing the number of replicate analyses for both calibration standards and samples. Although automated gas preparation techniques based on the H(3)PO(4) method (ISOCARB, Kiel device, Gas-Bench systems) have the potential to measure delta(CO)(2) (18)O efficiently for specific, slowly reacting phases (e.g. dolomite), problems associated with poorly defined alpha(CO)(2), (C) remain. The application of the Principle of Identical Treatment is not a solution to the analysis of these phases because it assumes that a single fractionation factor may be defined for each phase within a solid-solution regardless of its precise chemical composition. This assumption has yet to be tested adequately.     

Evaluating the utility of ion mobility separation in combination with high-pressure liquid chromatography/mass spectrometry to facilitate detection of trace impurities in formulated drug products

Many formulated products contain complex polymeric excipients such as polyethylene glycols (PEGs). Such excipients can be readily ionized by electrospray and may be present at very high concentrations, thus making it very difficult to identify trace level impurities such as degradants in samples, even if hyphenated techniques such as liquid chromatography/mass spectrometry (LC/MS) are used. Ion mobility (IM) spectrometry is a very rapid gas-phase separation technique and offers additional separation capability within the LC timeframe. This work investigates the use of an IM separator in combination with high-pressure liquid chromatography (HPLC) and MS, to improve the separation of drug-related materials from excipients, thus aiding the identification of trace-level impurities in an anti-HIV medication, Combivir.     

Determination of the Pesticide Fenbutatin Oxide in Tomatoes,Cucumbers and Bananas by High Performance Liquid Chromatographic/Atmospheric Pressure Chemical Ionization-Mass Spectrometry

A rapid method, using high-performance liquid chromatography (HPLC)/atmospheric pressure chemical ionization-mass spectrometry, has been developed for the determination of fenbutatin oxide in tomatoes, cucumbers and bananas. Samples were homogenized with sodium carbonate and ethyl acetate, filtered through sodium sulphate, concentrated and solvent exchanged into acetonitrile prior to analysis. HPLC was performed on a Hypercarb column with 10:90 acetic acid (5% v/v glacial acetic acid in water)/acetonitrile at a flow rate of 1 mL/min. Positive ionization selected-ion monitoring was performed on the 7 isotopic cluster ions from the tris(2-methyl-2-phenylpropyl) tin fragment. A comparison of solvent-based and extract-based standards showed that tomato and cucumber matrices had a slight enhancement effect on the signal intensity, whereas the banana matrix exerted a signal suppression effect. Calibration was linear over the range 0.25–5.0 ng/μL. The mean spike recoveries (extracts spiked at 0.5 mg/kg) were 88% for tomatoes and 80% for both cucumbers and bananas with relative standard deviations of 6%, 7% and 8% respectively. Limits of detection were commodity dependent and ranged from 0.06–0.12 ng/μL (equivalent to 0.01–0.02 mg/kg in the crop). Ionization was stable for long analytical time periods. © 1997 Crown Copyright     

Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.     

Comprehensive inter‐laboratory calibration of reference materials for δ18O versus VSMOW using various on‐line high‐temperature conversion techniques

Internationally distributed organic and inorganic oxygen isotopic reference materials have been calibrated by six laboratories carrying out more than 5300 measurements using a variety of high‐temperature conversion techniques (HTC) a in an evaluation sponsored by the International Union of Pure and Applied Chemistry (IUPAC). To aid in the calibration of these reference materials, which span more than 125‰, an artificially enriched reference water (δ¹⁸O of +78.91‰) and two barium sulfates (one depleted and one enriched in ¹⁸O) were prepared and calibrated relative to VSMOW2 b and SLAP reference waters. These materials were used to calibrate the other isotopic reference materials in this study, which yielded:

A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis

Metabonomic/metabolomic studies can involve the analysis of large numbers of samples for the detection of biomarkers and confidence in the analytical data, generated by methods such as GC and HPLC-MS, requires active measures on the part of the analyst. However, quality control for complex multi-component samples such as biofluids, where many of the components of interest in the sample are unknown prior to analysis, poses significant problems. Here the repeat analysis of a pooled sample throughout the run, thereby enabling the analysis to be monitored and controlled using targeted inspection of the data and pattern recognition, is advocated as a pragmatic solution to this problem.     

Optimization of HNO production from N,O-bis-acylated hydroxylamine derivatives

A wide range of N,O-bis-acylated hydroxylamine derivatives with chloro or arenesulfonyl leaving groups, and a related set of N-hydroxy-N-acylsulfonamides, have been synthesized and evaluated for nitroxyl (HNO) production. Mechanistic studies have revealed that the observed aqueous chemistry is more complicated than originally anticipated, and have been used to develop a new series of efficient HNO precursors (4u-4x, 7c-7d) with tunable half-lives.     

Spectroscopic analysis of bacterial biological warfare simulants and the effects of environmental conditioning on a bacterial spectrum

The ability to distinguish bacteria from mixed samples is of great interest, especially in the medical and defence arenas. This paper reports a step towards the aim of differentiating pathogenic endospores in situ, to aid any required response for hazard management using infrared spectroscopy combined with multivariate analysis. We describe a proof-of-principle study aimed at discriminating biological warfare simulants from common environmental bacteria. We also report an evaluation of multiple pre-processing techniques and subsequent differences in cross-validation of two pattern recognition models (Support Vector Machines and Principal Component–Linear Discriminant Analysis) for a six-class classification (bacterial classification). These classifications were possible with an average sensitivity of 88.0 and 86.9?%, and an average specificity of 97.6 and 97.5?% for the SVM and the PC-LDA models, respectively. Most spectroscopic models are built upon spectra from bacteria that have been specifically prepared for analysis by a particular method; this paper will comment upon the differences in the bacterial spectrum that occur between specific preparations when the bacteria have spent 30?days in the simulated weather conditions of a hot dry climate.

Rigid NON- and NSN-ligand complexes of tetravalent and trivalent uranium: comparison of U-OAr2 and U-SAr2 bonding

A rigid NSN-donor proligand, 4,5-bis(2,6-diisopropylanilino)-2,7-di-tert-butyl-9,9-dimethylthioxanthene (H(2)[TXA(2)], 1) was prepared by palladium-catalyzed coupling of 2,6-diisopropylaniline with 4,5-dibromo-2,7-di-tert-butyl-9,9-dimethylthioxanthene. Deprotonation of 1 using (n)BuLi provided Li(2)(DME)(2)[TXA(2)] (2), and subsequent reaction with UCl(4) afforded [Li(DME)(3)][(TXA(2))UCl(3)] (4). The analogous NON-donor ligated complex [(XA(2))UCl(3)K(DME)(3)] [3; XA(2) = 4,5-bis(2,6-diisopropylanilino)-2,7-di-tert-butyl-9,9-dimethylxanthene] was prepared by the reaction of K(2)(DME)(x)[XA(2)] with UCl(4). A cyclic voltammogram (CV) of 3 in THF/[NBu(4)][B(C(6)F(5))(4)] at 200 mV s(-1) showed an irreversible reduction to uranium(III) at E(pc) = -2.46 V versus FeCp(2)(0/+1), followed by a product wave at E(1/2) = -1.83 V. Complex 4 also underwent irreversible reduction to uranium(iii) [E(pc) = -2.56 V], resulting in an irreversible product peak at E(pa) = -1.83 V. One-electron reduction of complexes 3 and 4 using K(naphthalenide) under an argon atmosphere in DME yielded 6-coordinate [(XA(2))UCl(DME)] (5) and the thermally unstable 7-coordinate [(TXA(2))U(DME)Cl(2)Li(DME)(2)] (6), respectively. The U-S distances in 4 and 6 are uncommonly short, the C-S-U angles are unusually acute, and the thioxanthene backbone of the TXA(2) ligand is significantly bent. By contrast, the xanthene backbone in XA(2) complexes 3 and 5 is planar. However, κ(3)-coordination and an approximately meridional arrangement of the ancillary ligand donor atoms is maintained in all complexes. DFT and Atoms in Molecules (AIM) calculations were carried out on 3, 4, 5, 6, [(XA(2))UCl(3)](-) (3B), [(TXA(2))UCl(2)(DME)](-) (6B) and [(TXA(2))UCl(DME)] (6C) to probe the extent of covalency in U-SAr(2) bonding relative to U-OAr(2) bonding.