Scandium triflate and secondary amine promoted AA′B 2:1 coupling and formal inverse electron demand Diels-Alder reactions of dienals

Reaction prospecting studies resulted in the discovery of a Sc(OTf)₃ promoted novel AA′B 2:1 coupling of imidazolone or benzofuran substituted enals with morpholine. A related Sc(OTf)₃/morpholine promoted reaction was demonstrated for the coupling of a benzofuran substituted enal with dihydrofuran. The formation of these adducts is consistent with formal inverse electron demand Diels-Alder cycloadditions, most likely in a stepwise manner via a domino Michael-Mannich annulation process, involving iminium ion activation of the diene. A purely amine promoted formal inverse electron demand Diels-Alder cycloaddition approach was also demonstrated in the 2:1 coupling of 2,4-hexadienal with methanol. These reactions demonstrate the concepts of dual metal/amine catalysis and amine promoted formal inverse electron demand Diels-Alder cycloadditions. They differ from known examples of organocatalyzed Diels-Alder reactions, in which iminium ion activation of the dienophiles or enamine activation of the dienes occur.     

New tools for rapid clinical and bioagent diagnostics: microwaves and plasmonic nanostructures

In this timely review, we summarize recent work on ultra-fast and sensitive bioassays based on microwave heating, and provide our current interpretation of the role of the combined use of microwave energy and plasmonic nanostructures for applications in rapid clinical and bioagent diagnostics. The incorporation of microwave heating into plasmonic nanostructure-based bioassays brings new advancements to diagnostic tests. A temperature gradient, created by the selective heating of water in the presence of plasmonic nanostructures, results in an increased mass transfer of target biomolecules towards the biorecognition partners placed on the plasmonic nanostructures, enabling diagnostic tests to be completed in less than a minute, and in some cases only a few seconds, by further microwave heating. The diagnostic tests can also be run in complex biological samples, such as human serum and whole blood.     

Consideration of some sampling problems in the on-line analysis of batch processes by low-field NMR spectrometry

A low-field medium-resolution NMR spectrometer, with an operating frequency of 29 MHz for 1H, has been assessed for on-line process analysis. A flow cell that incorporates a pre-magnetisation region has been developed to minimise the decrease in the signal owing to incomplete polarisation effects. The homogeneous esterification reaction of crotonic acid and 2-butanol was monitored using a simple sampling loop; it was possible to monitor the progression of the reaction through changes in CH signal areas of butanol and butyl crotonate. On-line analysis of heterogeneous water-toluene mixtures proved more challenging and a fast sampling loop system was devised for use with a 5 L reactor. The fast sampling loop operated at a flow rate of 8 L min(-1) and a secondary sampling loop was used to pass a sub-sample through the NMR analyser at a slower (mL min(-1)) rate. It was shown that even with super-isokinetic sampling conditions, unrepresentative sampling could occur owing to inadequate mixing in the reactor. However, it was still possible to relate the 1H NMR signal obtained at a flow rate of 60 mL min(-1) to the composition of the reactor contents.     

Behavior of thin films of poly(oxyethylene)-poly(oxybutylene) copolymers studied by brewster angle microscopy and atomic force microscopy

Surface films of two copolymers of ethylene oxide (E) and butylene oxide (B), namely E23B8 and E87B18, have been examined by Brewster angle microscopy (BAM) and atomic force microscopy (AFM). Isotherms taken on unsupported films of these copolymers at the air-water interface showed a clear gas to liquid phase transition for E57B18 and a barely discernible phase transition for E23B8. The BAM studies showed a gradual brightening of the films as the surface pressure was increased, which was associated with a film thickening and/or a film densification. Several bright spots were also observed within the films, with the number of spots increasing gradually as the film surface pressure was increased. AFM studies of these films did not show any localized ordering, which fits in with the results from our previous X-ray study of these copolymers [Hodges, C. S.; Neville, F.; Konovalov, O.; Gidalevitz, D.; Hamley, I. W.; Langmuir 2006, 22 (21), 8821-8825], where no long-range ordering was observed. AFM imaging showed two sizes of particulates that were irregularly spaced across the film. The larger particulates were associated with silica contaminants from the copolymer synthesis, whereas the smaller particulates were assumed to be aggregated copolymer. An analysis of the semidilute region of the isotherm showed that while both copolymers had intermixed ethylene oxide and butylene oxide units, the lower molecular weight E23B8 copolymer manifested significantly more intermixing than E87B18.     

Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis

A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses.     

Limits of the plane wave approximation in the measurement of molecular properties

Rescattering electrons offer great potential as probes of molecular properties on ultrafast timescales. The most famous example is molecular tomography, in which high harmonic spectra of oriented molecules are mapped to "tomographic images" of the relevant molecular orbitals. The accuracy of such reconstructions can be greatly affected by the distortion of scattering wave functions from their asymptotic forms due to interactions with the parent ion. We investigate the validity of the commonly used plane wave approximation in molecular tomography, showing how such distortions affect the resulting orbital reconstructions.     

Selected ion flow tube study of the ion-molecule reactions of monochloroethene, trichloroethene, and tetrachloroethene

Data for the rate coefficients and product cations of the reactions of a large number of atomic and small molecular cations with monochloroethene, trichloroethene, and tetrachloroethene in a selected ion flow tube at 298 K are reported. The recombination energy of the ions range from 6.27 (H3O(+)) through to 21.56 (Ne(+)) eV. Collisional rate coefficients are calculated by modified average dipole orientation theory and compared with experimental values. Thermochemistry and mass balance predict the most feasible neutral products. Together with previously reported results for the three isomers of dichloroethene ( Mikhailov, V. A. ; Parkes, M. A. ; Tuckett, R. P. ; Mayhew, C. A. J. Phys. Chem. A 2006, 110, 5760 ), the fragment ion branching ratios have been compared with those from threshold photoelectron photoion coincidence spectroscopy over the photon energy range of 9-22 eV to determine the importance or otherwise of long-range charge transfer. For ions with recombination energy in excess of the ionization energy of the chloroethene, charge transfer is energetically allowed. The similarity of the branching ratios from the two experiments suggest that long-range charge transfer is dominant. For ions with recombination energy less than the ionization energy, charge transfer is not allowed; chemical reaction can only occur following formation of an ion-molecule complex, where steric effects are more significant. The products that are now formed and their percentage yields are a complex interplay between the number and position of the chlorine atoms with respect to the C=C bond, where inductive and conjugation effects can be important.