Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge"

The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength.     

Ruthenium(II) complexes of monodonor ligands: efficient reagents for asymmetric ketone hydrogenation

[Chemical reaction: See text] A series of BINOL-derived ligands have been prepared and incorporated into ruthenium(II) complexes containing a diamine ligand. The complexes have proven to be excellent catalysts for the asymmetric hydrogenation of ketones, giving reduction products with enantiomeric excesses of up to 99%.     

Molecular recognition and conductance in crown ethers

Crown ethers have the remarkable property of recognizing and binding specific metal cations in complex mixtures. We propose to combine molecular recognition with molecular electric conductance. The question we address is: can the event of binding a cation be sensed by a change in conductance? Specifically, we study a short molecular wire (MW) containing a crown-6 molecule connected via sulfur atoms to two gold atomic wires acting as metallic leads. Upon binding a cation, the density of states of the system is only slightly affected. This reflects the fact that the cation binding is largely electrostatic in nature and is accompanied by little electronic reorganization. Yet, the cationic binding does significantly lower conductance. We also identify strong interference affecting the conductance. A striking feature is the insensitivity of conductance to the type of ligand with the exception of the proton.     

Measuring intracellular calcium fluxes in high throughput mode

The measurement of intracellular calcium fluxes in real time is widely applied within the pharmaceutical industry to measure the activation of G-protein coupled receptors (GPCRhyp;s), either for pharmacological characterisation or to screen for new surrogate ligands. Initially restricted to G(q) coupled GPCRs, the introduction of promiscuous and chimeric G-proteins has further widened the application of these assays. The development of new calcium sensitive dyes and assays has provided sensitive, homogeneous assays which can be readily applied to high throughput screening (HTS). In this paper we describe the full automation of this assay type using a fluorometric imaging plate reader (FLIPR ) integrated into a Beckman/Sagian system to establish a simple robotic system that is well suited for the current medium throughput screening in this area of lead discovery. Using a recently completed HTS we discuss important determinants for FLIPR based screening, highlight some limitations of the current approach, and look at the requirements for future automated systems capable of keeping up with expanding compound files.     

A small angle X-ray scattering study of polyethylene fibres,using the two-dimensional correlation function

Summary By Fourier transformation of the intensity distribution in the small angle X-ray scattering diagram of a polymer fibre one obtains the corresponding two-dimensional correlation function. This is compared with correlation functions calculated on the basis of different models of the semi-crystalline morphology. Here, two steps may be distinguished: in the first, the correctness of a model may be checked with the aid of qualitative features, such as the relative positions and sizes of positive and negative areas; in the second a quatitative agreement is pursued by fixing the various parameters involved. This method was applied to cold drawn low density polyethylene before and after annealing at different temperatures. In the case of the non-annealed sample, the microparacrystalline model, discussed byHosemann andLoboda-Cackovic (J. Appl. Cryst.11, 540 (1978)) was found to give the best fit. Annealing at 80 °C or higher temperatures seems to lead to what has been indicated as a three-dimensional chess-board structure; it consists of fibrils in which crystalline and amorphous regions alternate in such a way that the crystalline regions in a fibril are adjacent to amorphous regions in neighbouring fibrils.

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Zusammenfassung Durch Fourier-Transformation der Intensitätsverteilung im Kleinwinkelstreudiagramm von Polymerfasern bekommt man die zugehörige zweidimensionale Korrelationsfunktion. Diese wird verglichen mit Korrelationsfunktionen, die für verschiedene Modelle der teilkristallinen Morphologie berechnet wurden.Hier werden zwei Schritte unterschieden. Im ersten Schritt wird die Richtigkeit eines Modells überprüft mit Hilfe von qualitativen Merkmalen, wie z. B. die relativen Lagen und Größen der positiven und negativen Bereiche. Im zweiten Schritt wird eine quantitative Übereinstimmung dadurch angestrebt, daß die unterschiedlich bezüglichen Parameter festgestellt werden. Diese Methode wurde angewandt bei kaltverstrecktem Polyäthylen niedriger Dichte, sowohl vor wie nach Temperung bei verschiedenen Temperaturen. Im Falle einer nicht getemperten Probe zeigte sich, daß das mikrokristalline Modell, vorgeschlagen von Hosemann und Loboda-Cackovic (J. Appl. Cryst.11, 540 (1978)), am besten zutrifft. Temperung bei 80°C oder bei höheren Temperaturen scheint zu einer Struktur zu führen, die als dreidimensionale Schachbrett-Struktur bezeichnet wurde. Sie besteht aus Fibrillen, in denen kristalline und amorphe Bereiche abwechseln, und zwar so, daß die kristallinen Bereiche in einer Fibrille nur von amorphen Bereichen in nächstliegenden Fibrillen umgeben sind.

     

Enzymatic hydrogen atom abstraction from polyunsaturated fatty acids

The oxidation of polyunsaturated fatty acids such as arachidonic and linoleic acid initiates a plethora of cell signaling pathways in animals and plants. The chemistry of the enzymatic oxidation has been investigated for several enzymes, most notably prostaglandin synthase and the lipoxygenases, revealing many surprises and impressive examples of enzymatic control of hydrogen atom abstraction and subsequent oxygenation.     

Rhodium-catalyzed reductive aldol reactions using aldehydes as the stoichiometric reductants

Chelated acyl rhodium hydrides, generated from the addition of [Rh(dppe)]ClO4 to beta-sulfide-substituted aldehydes, can function as the stoichiometric reductants in reductive aldol processes. Unsaturated nitriles, esters, and ketones can be used as enolate equivalents, and a variety of simple alpha- and beta-substituted aldehydes can be employed. The use of a second, more electrophilic, aldehyde allows three-component reactions to be performed.     

Olefin oxygenation by the hydroperoxide adduct of a nonheme manganese(IV) complex: epoxidations by a metallo-peracid produces gentle selective oxidations

The reactive intermediates and mechanisms of oxygenation of olefins by manganese complexes were investigated by treating olefins with newly synthesized [MnIV(Me2EBC)(OH)2](PF6)2 in the presence and absence of peroxide and by studying its catalytic epoxidation reaction in normal aqueous solution and, individually, with isotopically labeled H218O, 18O2, and H218O2. The manganese oxo species is not the reactive intermediate for the oxygen transfer process mediated by this manganese complex. A novel manganese(IV) peroxide intermediate, MnIV(Me2EBC)(O)(OOH)+, was captured by mass spectrometry and is proposed as the intermediate that oxygenates olefins in this catalytic system.     

Analysis of 19-norandrosterone in human urine by gas chromatography–isotope-dilution mass spectrometry: method adopted by LGC for participation in the Comité Consultatif pour la Quantité de Matière (CCQM) Pilot Study P68

The method used at LGC for analysis of “total” 19-norandrosterone (19-norandrosterone glucuronide plus “free” 19-norandrosterone) in urine for the Comité Consultatif pour la Quantité de Matière Pilot Study (CCQM-P68) is described. The analytical method used was a modified version of the method developed at the National Measurement Institute of Australia, which used a hydrolysis and derivatisation procedure first described by the German Sports University. This method is routinely used by World Anti-Doping Agency-accredited laboratories for sports drug testing. The main modifications made to the method were the use of 19-norandrosterone glucuronide as a calibration standard and 19-norandrosterone glucuronide-d4 as an isotopically labelled internal standard, and the use of a bench-top quadrupole gas chromatograph–mass spectrometer. The results produced by LGC (2.14 ± 0.15 ng g⁻¹ expanded uncertainty, coverage factor k = 2) were in excellent agreement with those from other participating national metrology institutes and thus further validates the exact-matching isotope-dilution mass spectrometric procedures used at LGC for a wide range of reference measurement applications, including measurement of ng g⁻¹ levels of steroids in a biological matrix.     

Non-linear dielectric spectroscopy: antifouling and stabilisation of electrodes by a polymer coating

Non-linear dielectric spectroscopy (NLDS) has previously been shown to produce quantitative information that is indicative of the metabolic state of various organisms, by modeling the non-linear effects of their membranous enzymes on an applied oscillating electromagnetic field using supervised multivariate analysis methods. However, the instability of the characteristics of the measuring apparatus rendered the process temperamental at best in the laboratory and impractical for field use. The main practical problem, of the non-stationarity of the electrode-solution interface and the ease with which the electrode surfaces are subject to protein fouling. It is addressed by applying a thin, electrically transparent antifouling coat to the electrodes. This reduces the interminable cleaning procedures previously required to prepare the electrodes for use, increases their usable lifetime before recleaning, and also improves the precision and linearity of multivariate models on NLDS data.