The IRMM International Measurement Evaluation Programme (IMEP) IMEP-4: Trace elements (Li, Cu, Zn) in serum

The aim of the International Measurement Evaluation Programme (IMEP) is to give an objective picture of state-of-the-practice analytical measurements by comparing them to a reference value obtained by a primary method of measurement. The referencevalue is therefore as traceable to the SI system of measurements as can presently be achieved and is independent of human or political decisions. Thus a large scale field test is made to achieve (international) comparability of measurements by comparing them with an independent metrologically established value. In the fourth measurement round, IMEP-4, three trace elements, Li, Cu and Zn, at three different levels in (bovine) serum were measured by about 12 participating laboratories using their routine methods. The (coded) results are graphically reported and compared to certified reference values established by an isotope-specific method, isotope dilution mass spectrometry, defined as a primary method of measurement by the Consultative Committee on Amount of Substance. Results indicate a spread of more than ±50%, asymmetrically distributed around the reference value with its own uncertainty range, although the self-declared accuracy of the laboratories was 5–10%. Self-assessment by participants of their analytical capabilities does not show a high correlation between self-rating ("more experienced" or "less experienced") and actual performance. In the way they have been applied, all methods seem to produce results of approximately the same quality.     

2-Halo-diketopiperazines as chiral glycine cation equivalents

A range of (2S,5S)-5-isopropyl-2-halo-N,N′-bis-(p-methoxybenzyl)-piperazine-3,6-diones 8 (Cl), 11, 12 (F) and 13 (Br) have been prepared, either via electrophilic halogenation of the corresponding lithiated diketopiperazine, or via transhalogenation from fluoro-11 and 12. The product distribution and stereoselectivity of additions of allyltrimethylsilane, sodium thiophenolate and a range of organomagnesium reagents to chloro 8 are reported. In the reactions with Grignard reagents the observed stereo- and regioselectivities are dependent on the reagent employed, with C-3 carbonyl addition products predominating upon addition of allyl or methylmagnesium chloride and stereodivergent formal C-2 addition predominating with benzyl or isopropylmagnesium chloride. A model to account for the different reactivity and stereoselectivity in these reactions is proposed.     

Iodine-mediated ring-closing iodoamination with concomitant N-debenzylation for the asymmetric synthesis of polyhydroxylated pyrrolidines

Treatment of a range of homochiral unsaturated β-amino esters (containing a cis-dioxolane unit) with iodine promotes a novel ring-closing alkene iodoamination reaction which proceeds with concomitant N-debenzylation, providing a simple and stereoselective route to iodomethyl pyrrolidines. Functional group interconversion of the resulting iodomethyl pyrrolidines upon treatment with AgOAc proceeds via the corresponding aziridinium ion, with subsequent deprotection giving access to polyhydroxylated pyrrolidines.     

Advances in clinical chemistry over the past 25 years

A survey is presented of developments over the past 25 years of several important areas of clinical chemistry. These areas are instrumentation, reagents, electrochemical sensors, computing, statistics, quality control, enzymology, drug monitoring, trace elements and nucleic acid probes.     

Kinetic resolution and parallel kinetic resolution of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives

Conjugate addition of lithium dibenzylamide to methyl 5-isopropyl, 5-phenyl- and 5-tert-butyl-cyclopentene-1-carboxylates occurs with high levels of substrate control (>88% de), with preferential addition to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the stereodirecting 5-alkyl substituent. Treatment of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with both lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide and lithium (+/-)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide indicates significant enantiorecognition in their mutual kinetic resolutions, with preferential addition anti- to the 5-alkyl substituent, giving the 1,2-syn-1,5-anti-arrangement (E >16) after enolate protonation anti- to the amino functionality. The kinetic resolution of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with lithium (S)-N-benzyl-N-alpha-methylbenzylamide, and their efficient parallel kinetic resolution with a pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide are also demonstrated, giving a range of 5-alkyl-cispentacin derivatives in >98% de and high ee after N-deprotection.     

The drag of three-dimensional rectangular cavities

Cavities and other surface cut-outs are present on aircraft in numerous forms, from cargo bays and landing gear housing to rivet depressions and panel handles. Although these surface imperfections make a significant contribution to the overall drag on an aircraft, relatively little is known about the flow mechanisms associated with cavities, particularly those which have a strongly three-dimensional geometry. The present work is a wind tunnel investigation of the drag forces and flow regimes associated with cavities having a 2:1 rectangular planform geometry. The effects of both the cavity depth and the flow incidence angle have been examined in terms of the overall cavity drag increment and the mean surface pressure distributions. The drag forces have been determined from both integrated pressures and direct force balance measurements. For the model normal to the flow direction the flow within the cavity was remarkably symmetrical in all the configurations examined. In most cases the cavity flow is dominated by a single large eddy. However, for cavities yawed to other incidence angles there is considerable flow asymmetry, with strong vorticity shedding and high drag in some cases, notably with depth/narrowest width ratio of 0.4–0.5 at 45–60° incidence. The present data correspond well with established results and extend the scope of information available for design purposes and for the development of numerical models.Nomenclature A _p planform area of model - C _D pressure drag coefficient (F _D /(A _p · q)) - C _D drag coefficient increase due to cavity (C _D – c_f) - c _f local skin friction coefficient - C _L pressure lift coefficient (F _L /(A _p · q)) - C _p mean surface pressure coefficient (P – P _s )/q) - F _D drag force - F _L lift force - h depth - L longest planform dimension of model - P surface pressure on model - P _s freestream static pressure - P _t freestream total pressure - q freestream dynamic pressure (P _t – P_s) - Re Reynolds number (U _R · W/v) - U _R freestream velocity - W narrowest planform dimension of model - Z vertical cartesian coordinate - incidence angle - kinematic viscosity     

"Pure by NMR"?

Integration of a (13)C-(1)H satellite peak of a given (12)C-(1)H parent resonance within a quantitative (1)H NMR spectrum and comparison to the minor component represents a simple protocol for the accurate determination of diastereoisomeric ratios of up to 1000:1 (i.e., 99.8% de).     

Alkylation and aldol reactions of acyl derivatives of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates α-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH₄ to give enantiopure α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes in good yield.