Cyclosporin Measurement – who cares about inaccuracy?

Most medical laboratories measure the immunosuppressive drug cyclosporin using one of a number of commercial immunoassays, or high-performance liquid chromatography (HPLC). The calibration of these assays is based on material supplied by the kit manufacturers or prepared in-house. We have examined inaccuracy for the measurement of cyclosporin in samples spiked to known concentrations and the impact of any inaccuracy on the results for cyclosporin measurement in pooled samples from patients prescribed the drug. The data were from the International Cyclosporin Proficiency Testing Scheme, based on aliquots of cyclosporin-free blood to which known amounts of the drug had been added or aliquots of pooled samples collected from patients receiving cyclosporin. Compared with the results using HPLC, the immunoassays had a median bias which ranged from –4.5% to 8.2% for the spiked samples. When pooled samples from patients were analysed the percentage difference from the measured HPLC value, allowing for assay inaccuracy, was as high as 29.9%. It is concluded that inaccuracy is a factor in between-assay performance for this measurement and that proficiency testing schemes should attempt to put more emphasis on this aspect of assay performance.     

‘Good enough’ performance measurement: a trade-off between activity and action

Performance measurement systems along the lines of the EFQM and the balanced scorecard have developed rapidly in recent years, and now occupy much management time and effort. There is limited evidence that performance improvement has received proportionate attention. Six organisations selected for their success were studied using a grounded theory approach based on interviews with management accountants and operations managers in each of the organisations. It is clear that they are all making strenuous efforts to use their performance measurement systems but with a focus on the ‘good enough’ rather than the detail. This gave managers in these organisations the time and space to concentrate on the use of performance measures on forward looking relevance, understanding and action, rather than retrospective and detailed control. This approach was promoted by senior managers and was based on their ability to see the business in simple terms and their understanding of the key drivers of business performance.     

Porphyrin-containing molecular capsules: metal mediated dimerization of a bis-porphyrin cavity

[reaction] A self-complementary V-shaped bis-porphyrin cavity has been synthesized that is capable of dimerization to form a capsule structure. Self-assembly of the dimer occurs via metal ion coordination and produces an internal volume for guest encapsulation.     

Metallostars: high-nuclearity linearly developed nanostructures containing multiple cluster motifs

Metallostars are complexes in which a single branching site bears a number of metallated arms. Although they are related to metallodendrimers, they have the advantage of being capable of extending in an unlimited sense; in contrast to metallodendrimers, steric interactions decrease with increasing generation number. In this paper a series of polyalkyne stars with four and six arms, based upon a single tetrahedral carbon core and a benzene core, respectively, are reported and their reactions with [Co2(CO)8] to give metallostars that contain multiple [C2Co2(CO)6] motifs are described.     

Synthesis of arene-soluble mixed-metal Zr/Ce,Zr/Y,and related [[Zr2(OiPr)9]LnX2]n complexes using the dizirconium nonaisopropoxide ligand

The utility of polydentate monoanionic [Zr2(OiPr)9]- in generating arene-soluble, unsolvated, mixed-metal Zr/Ce and Zr/Y complexes is described. The synthesis of other mixed-metal zirconium lanthanide complexes was also studied to explore the relationship of metal size to structure. Lanthanide trihalides react in THF with KZr2(OiPr)9 to form unsolvated dimers, [[Zr2(OiPr)9]LnCl2]2, with the larger metals, Ln = Ce (1), Ho (2), Y (3), and unsolvated monomers, [Zr2(OiPr)9]LnCl2, with the smaller elements, Ln = Er (4), Yb (5). The synthesis of a monomeric iodide analogue, [Zr2(OiPr)9]TmI2, 6, by reduction of Zr2(OiPr)8(iPrOH)2 with TmI2(DME)3 is also reported. In all of these complexes, the [Zr2(OiPr)9]- subunit is tetradentate. 1-6 are compared with related cyclopentadienyl halide complexes to evaluate the special features of the dizirconium nonaisopropoxide ligand versus cyclopentadienide.     

Structure elucidation with lanthanide-induced shifts. 4—Bound shifts vs relative shifts

The use of lanthanide shift reagents (LSR's) to obtain additional structural information from nuclear magnetic resonance studies has gained widespread acceptance. However, there has not been general agreement with regard to the most appropriate methodology for analysis of the shifted NMR spectra. We present arguments that only the bound shifts (Δ₁) corresponding to the LS complex should be used for correlation of lanthanide-induced shifts with molecular structure by means of the pseudocontact equation. Several examples are discussed of compounds for which the relative induced shifts are dependent on the concentration of LSR. For such cases it is not possible for both Δ₁ and Δ₂ (the bound shift corresponding to the LS₂ complex) to correlate successfully with the correct structure. Alternative methods of obtaining bound shifts are critically evaluated.     

Scattered-electron rejection in electron transmission spectroscopy

The rejection of scattered electrons in magnetically collimated transmission spectrometers which employ trochoidal monochromators is discussed. Two rejection mechanisms are described. We show that at low impact energies electrons backscattered into the monochromator contribute substantially to the rejection. At higher energies, rejection at the retarding plate following the collision chamber is the dominant mechanism. Under conditions in which the scattered electrons are only partly rejected, artifacts can appear in the measured spectra. We derive a simple model which qualitatively reproduces these features.     

The experimental gas-phase structures of 1,3,5-trisilylbenzene and hexasilylbenzene and the theoretical structures of all benzenes with three or more silyl substituents

The structures of 1,3,5-trisilylbenzene and hexasilylbenzene in the gas phase have been determined by electron diffraction, and that of 1,3,5-trisilylbenzene by X-ray crystallography. The structures of three trisilylbenzene isomers, three tetrasilylbenzenes, pentasilylbenzene and hexasilylbenzene have been computed, ab initio and using Density Functional Theory, at levels up to MP2/6-31G*. The primary effect of silyl substituents is to narrow the ring angle at the substituted carbon atoms. Steric interactions between silyl groups on neighbouring carbon atoms lead first to displacement of these groups away from one another, and then to displacement out of the ring plane, with alternate groups moving to opposite sides of the ring. In the extreme example, hexasilylbenzene, the SiCCSi dihedral angle is 17.8(8) degrees .     

Electrochemistry in ultrahigh vacuum: underpotential deposition of Al on polycrystalline W and Au from room temperature AlCl(3)/1-ethyl-3-methylimidazolium chloride melts

The voltammetric characteristics of polycrystalline Au and W electrodes cleaned (thermal annealing at 1100 K) and characterized (Auger electron spectroscopy) in ultrahigh vacuum (UHV) have been examined in ultrapure AlCl(3)/1-ethyl-3-methylimidazolium chloride (EtMeImCl) melts in UHV. These experiments were performed using a custom-designed transfer system that allows for the all-Al electrochemical cell to be filled with EtMeImCl in an auxiliary UHV chamber and later transferred under UHV to the main UHV chamber that houses the Auger electron spectrometer. The results obtained for the underpotential (UPD) and bulk deposition of Al on Au were found to be very similar to those reported in the literature for measurements carried out under 1 atm of an inert gas in a glovebox. For the far more reactive W surfaces, voltammetric features ascribed to the stripping of underpotential-deposited Al could be observed following a single scan from 1.0 V vs Al(3+)/Al to a potential negative enough for bulk deposition of Al to ensue. This behavior is unlike that reported in the literature for experiments performed in a glovebox, which required either extensive potential cycling in the Al bulk deposition and stripping region or excursions to potentials positive enough for chlorine evolution to ensue for Al UPD features to be clearly discerned. These observations open new prospects for fundamental electrochemical studies of well-characterized, highly reactive metals, including single crystals, in a variety of low vapor pressure ionic liquids.