Encapsulation of transition metal atoms into carbon nanotubes: a supramolecular approach

A functionalised fullerene incorporating a double-chelating group binds transition metal cations and acts as an effective vehicle for delivering metals into carbon nanotubes.     

A digital microfluidic method for multiplexed cell-based apoptosis assays

Digital microfluidics (DMF), a fluid-handling technique in which picolitre-microlitre droplets are manipulated electrostatically on an array of electrodes, has recently become popular for applications in chemistry and biology. DMF devices are reconfigurable, have no moving parts, and are compatible with conventional high-throughput screening infrastructure (e.g., multiwell plate readers). For these and other reasons, digital microfluidics has been touted as being a potentially useful new tool for applications in multiplexed screening. Here, we introduce the first digital microfluidic platform used to implement parallel-scale cell-based assays. A fluorogenic apoptosis assay for caspase-3 activity was chosen as a model system because of the popularity of apoptosis as a target for anti-cancer drug discovery research. Dose-response profiles of caspase-3 activity as a function of staurosporine concentration were generated using both the digital microfluidic method and conventional techniques (i.e., pipetting, aspiration, and 96-well plates.) As expected, the digital microfluidic method had a 33-fold reduction in reagent consumption relative to the conventional technique. Although both types of methods used the same detector (a benchtop multiwell plate reader), the data generated by the digital microfluidic method had lower detection limits and greater dynamic range because apoptotic cells were much less likely to de-laminate when exposed to droplet manipulation by DMF relative to pipetting/aspiration in multiwell plates. We propose that the techniques described here represent an important milestone in the development of digital microfluidics as a useful tool for parallel cell-based screening and other applications.     

Contrast and resolution enhancement in a confocal terahertz video system

The effect of image contrast enhancement without the loss of the spectral composition of the radiation under investigation has been experimentally demonstrated for a terahertz far-field video system. The result has been obtained by using a confocal aperture placed in the intermediate-focus region of the optical system. The result is a fundamental advance towards the achievement of subwavelength resolution and the contrast of microscopy video systems in the terahertz spectral range.     

A C alpha-H...O hydrogen bond in a membrane protein is not stabilizing

Hydrogen bonds involving a carbon donor are very common in protein structures, and energy calculations suggest that Calpha-H...O hydrogen bonds could be about one-half the strength of traditional hydrogen bonds. It has therefore been proposed that these nontraditional hydrogen bonds could be a significant factor in stabilizing proteins, particularly membrane proteins as there is a low dielectric and no competition from water in the bilayer core. Nevertheless, this proposition has never been tested experimentally. Here, we report an experimental test of the significance of Calpha-H...O bonds for protein stability. Thr24 in bacteriorhodopsin, which makes an interhelical Calpha-H...O hydrogen bond to the Calpha of Ala51, was changed to Ala, Val, and Ser, and the thermodynamic stability of the mutants was measured. None of the mutants had significantly reduced stability. In fact, T24A was more stable than the wild-type protein by 0.6 kcal/mol. Crystal structures were determined for each of the mutants, and, while some structural changes were seen for T24S and T24V, T24A showed essentially no apparent structural alteration that could account for the increased stability. Thus, Thr24 appears to destabilize the protein rather than stabilize. Our results suggest that Calpha-H...O bonds are not a major contributor to protein stability.     

Single-site beta-diiminate zinc catalysts for the alternating copolymerization of CO2 and epoxides: catalyst synthesis and unprecedented polymerization activity

Synthetic routes to zinc beta-diiminate complexes are reported. The synthesis of 11 beta-diimine [(BDI)-H] ligands, with varying N-aryl substituents and bridging structures, is described. These ligands are converted to (BDI)ZnX complexes (X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr). X-ray structural data revealed that all zinc complexes examined exist as micro-X-bridged dimers in the solid state, with the exception of the zinc ethyl and amido complexes which were monomeric. Complexes of the form (BDI)ZnOR (R = alkyl, acyl) and (BDI)ZnN(SiMe3)2 are highly active catalysts for the alternating copolymerization of epoxides and CO2. Copolymerizations of cyclohexene oxide (CHO) and CO2 with (BDI-1)ZnX [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene)] and (BDI-2)ZnX [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2-pentene)], where X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr, were attempted at 50 degrees C and 100 psi CO2. Complexes with X = OAc, N(SiMe3)2, OMe, O(i)Pr all produced polycarbonate by the alternated insertion of CHO and CO2 with similar catalytic activities, comparable molecular weights, and narrow molecular weight distributions (MWD approximately 1.1), indicating the copolymerizations are living. Furthermore, ligand effects were shown to dramatically influence the polymerization activity as minor steric changes accelerated or terminated the polymerization activity.     

Poly[2,2-dimethyl-4-(methoxylcarbonyl) butylene]: Synthesis with an ethylaluminum sesquichloride–peroxide initiator and NMR characterization

The alternating copolymer of isobutylene and methyl acrylate (the polymer of the title) has been obtained by using ethylaluminum sesquichloride (AlEt_1.5Cl_1.5) and 2-methylpentanoyl peroxide as the initiating system in benzene solution. The alternating copolymer is obtained at an acrylate/Al molar ratio of 17. Higher ratios increase the level of acrylate residues in the copolymer isolated; in the absence of AlEt_1.5Cl_1.5, an equal molar feed gives a copolymer with 75 mole % acrylate units. ¹H- and ¹³C-NMR spectra have been used to study the details of polymer structure and support the equal molar, alternating nature of the macromolecule. The details of the methoxy and gem-dimethyl peaks in the PMR spectra are consistent with a Bernoullian process determining the polymer configurational sequences, with P_m = 0.55–0.60.     

Pyrazolo[1,5-a]pyridines as p38 kinase inhibitors

[reaction: see text] A convergent synthesis of substituted pyrazolo[1,5-a]pyridines has been achieved either via a regioselective [3 + 2] cycloaddition of N-aminopyridines with alkynes or by thermal cyclization of disubstituted azirines. Subsequent palladium-catalyzed introduction of pyridines or de novo synthesis of pyrimidines affords inhibitors of p38 kinase.