Combined experimental and theoretical study of the mechanism and enantioselectivity of palladium- catalyzed intermolecular Heck coupling

The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods. The reaction follows Halpern-style selectivity; that is, the major isomer is produced from the least favored form of the pre-insertion intermediate. The initially formed Ph-Pd(P,N) species prefers a geometry with the phenyl trans to N. However, the alternative form, with Ph trans to P, is much less stable but much more reactive. In the preferred transition state, the phenyl moiety is trans to P, but significant electron density has been transferred to the alkene carbon trans to N. The steric interactions in this transition state fully account for the enantioselectivity observed with the ligands studied. The calculations also predict relative reactivity and nonlinear mixing effects for the investigated ligands; these predictions are fully validated by experimental testing. Finally, the low conversion observed with some catalysts was found to be caused by inactivation due to weak binding of the ligand to Pd(0). Adding monodentate PPh3 alleviated the precipitation problem without deteriorating the enantioselectivity and led to one of the most effective catalytic systems to date.     

A concerted mechanism for uncatalysed transfer of carbon substituents from diimides to C = C and C[triple bond]C

We present high-level computational predictions regarding a novel uncatalysed, yet feasible, C-C bond forming reaction.     

Infrared spectroscopy of Landau levels of graphene

We report infrared studies of the Landau level (LL) transitions in single layer graphene. Our specimens are density tunable and show in situ half-integer quantum Hall plateaus. Infrared transmission is measured in magnetic fields up to B=18 T at selected LL fillings. Resonances between hole LLs and electron LLs, as well as resonances between hole and electron LLs, are resolved. Their transition energies are proportional to sqrt[B], and the deduced band velocity is (-)c approximately equal to 1.1 x 10(6) m/s. The lack of precise scaling between different LL transitions indicates considerable contributions of many-particle effects to the infrared transition energies.     

Early effects of radiation radical pairs in a single crystal of bartituric acid

Radical pairs are formed and trapped when barbituric acid is irradiated with electrons at 77 K. The radical pairs were identified and the molecular structure determined in single crystal studies. The two unpaired species, constituting the pair, were found to be identical and equal to the isolated radical previously studied. The radical is formed by a hydrogen abstraction from C ₅, and the pair is formed by two such abstractions in neighbour molecules. The pair formation is quite selective and involve exclusively the nearest neighbour molecules.     

Julia Sets of Orthogonal Polynomials

Potential Analysis - For a probability measure with compact and non-polar support in the complex plane we relate dynamical properties of the associated sequence of orthogonal polynomials {Pn} to...     

Araiosamines A-D: tris-bromoindole cyclic guanidine alkaloids from the marine sponge Clathria (Thalysias) araiosa

Four new tris-bromoindole cyclic guanidine alkaloids, araiosamines A-D, were isolated from the methanol extract of a marine sponge, Clathria (Thalysias) araiosa, collected from Vanuatu. Their carbon skeletons delineate a new class of indole alkaloids apparently derived from a linear polymerization process involving a carbon-carbon bond formation. Comparison of the structures including the relative configurations suggests a common intermediate containing a dihydroaminopyrimidine moiety capable of undergoing various modalities of conjugate addition to yield unprecedented ring systems.     

Laser control of chemical reactions

Chemical reactions are at the heart of chemistry and the dream of controlling the outcome of these reactions is an old one. Thus, with given reactants, a solvent and perhaps assisted by a catalyst, we would like to 'steer' the reactants into a particular desired product. This review focuses on how to control the dynamics of chemical reactions, beyond traditional temperature control, with the emphasis on unimolecular reactions. The electromagnetic radiation of lasers can induce so-called coherent dynamics. The recent theoretical and experimental results on this coherent control are explained and illustrated with computational and experimental examples.     

Prolonged T1 in patients with liver cirrhosis: an in vivo MRI study

Fifteen patients with liver cirrhosis and two control groups were examined. The first control group consisted of 7 healthy volunteers, and the second group of 17 patients with nonfocal liver diseases. The T1 and T2 relaxation times were calculated from signal intensities read out from a region of interest centrally located in the liver. T1 relaxation time was longer in the patients with liver cirrhosis than in the two reference groups. Ten patients had a liver biopsy taken prior to the MRI study. No correlation was found between histopathology and the measured relaxation times.     

MR pulse sequences for selective relaxation time measurements: a phantom study

The accuracy of relaxation time measurements of spectroscopic inversion recovery and CPMG multi-echo pulse sequences together with ISIS and stimulated echo-pulse methods have been tested on a reference phantom (test object no. 5, of the EEC Concerted Research Project). For the measurements a Siemens Magnetom wholebody magnetic resonance scanner operating at 1.5 Tesla was used. For comparison six imaging pulse sequences for relaxation time measurements were tested on the same phantom. The spectroscopic pulse sequences all had an accuracy better than 10% of the reference values.     

Profiling of multiple signal pathway activities by multiplexing antibody and GFP-based translocation assays

Multiplexing of GFP based and immunofluorescence translocation assays enables easy acquisition of multiple readouts from the same cell in a single assay run. Immunofluorescence assays monitor translocation, phosphorylation, and up/down regulation of endogenous proteins. GFP-based assays monitor translocation of stably expressed GFP-fusion proteins. Such assays may be multiplexed along (vertical), across (horizontal), and between (branch) signal pathways. Examples of these strategies are presented: 1) The MK2-GFP assay monitors translocation of MK2-GFP from the nucleus to the cytoplasm in response to stimulation of the p38 pathway. By applying different immunofluorescent assays to the MK2 assay, a multiplexed HCA system is created for deconvolution of p38 pathway activation including assay readouts for MK2, p38, NFkappaB, and c-Jun. 2) A method for evaluating GPCR activation and internalization in a single assay run has been established by multiplexing GFP-based internalization assays with immunofluorescence assays for downstream transducers of GPCR activity: pCREB (cAMP sensor), NFATc1 (Ca(2+) sensor), and ERK (G-protein activation). Activation of the AT1 receptor is given as an example. 3) Cell toxicity readouts can be linked to primary readouts of interest via acquisition of secondary parameters describing cellular morphology. This approach is used to flag cytotoxic compounds and deselect false positives. The ATF6 Redistribution assay is provided as an example. These multiplex strategies provide a unique opportunity to enhance HCA data quality and save time during drug discovery. From a single assay run, several assay readouts are obtained that help the user to deconvolute the mode of action of test compounds.