Reaction of Aryl Iodides with (PCP)Pd(II)—Alkyl and Aryl Complexes: Mechanistic Aspects of Carbon—Carbon Bond Formation

The reaction of the PCP-type complex Pd(Me){2,6-(ⁱPr₂PCH₂)₂C₆H₃}( 3 ) with phenyl iodide results in the formation of Pd(I){2,6-(ⁱPr₂PCH₂)₂C₆H₃} ( 5 ), methyl iodide, toluene, and biphenyl. Formation of Pd(Ph){2,6-(ⁱPr₂PCH₂)₂C₆H₃}( 4 ) is observed during the reaction by ³¹P NMR. Reaction of 4 with aryl iodides results in the formation of 5 and Ph–Ph, Ph–Ar, and Ar–Ar, products indicative of a radical reaction. Under pseudo-first-order conditions, the rates of the reactions follow the order p-OMe > p-Me > H > p-NO₂ > m-Cl. The reaction is likely to involve electron transfer from 4 to the aryl iodide followed by fast decomposition of a postulated radical cation [Pd(Ph){2,6-(ⁱPr₂PCH₂)₂C₆H₃}]^+. ( 4 ^+.) to give a phenyl radical and [Pd{2,6-(ⁱPr₂PCH₂)₂C₆H₃}]⁺ ( 6 ⁺). Facile decomposition of the aryl iodide radical anion generates an aryl radical and I⁻. Recombination of aryl radicals gives rise to mixed biaryls, and 6 ⁺ combines with I⁻ to give 5 .     

Electrochemical detection of single-nucleotide mismatches: application of M-DNA

The detection of a single-nucleotide mismatch in unlabeled duplex DNA by electrochemical methods is presented. Impedance spectroscopy is used to characterize a perfect duplex monolayer and three DNA monolayers differing in the position of the mismatch. The monolayers were studied as B-DNA (normal duplex DNA) and after conversion to M-DNA (a metalated duplex). Modeling of the impedance data to an equivalent circuit provides parameters that are useful in discriminating the four monolayer configurations. The resistance to charge transfer, R(CT), was lower for all duplexes after conversion to M-DNA. Contrary to expectations, R(CT) was also found to decrease for duplexes containing a mismatch. However, R(CT) was found to be diagnostic for mismatch detection. In particular, the difference in R(CT) between B- and M-DNA (deltaR(CT)) decreased from 190(22) omega.cm(2) for a perfectly matched duplex to 95(20), 30(20), and 85(20) omega.cm(2) for a mismatch at the top (distal), middle, and bottom (proximal) positions of the monolayer with respect to the gold surface. Further, a method to form loosely packed single-stranded (ss)-DNA monolayers by duplex dehybridization that is able to rehybridize to target strands is presented. Rehybridization efficiencies were in the range of 40-70%. Under incomplete hybridization conditions, the R(CT) was the same for matched and mismatched duplexes under B-DNA conditions. However, deltaR(CT) between B- and M-DNA, under incomplete hybridization, still provided a distinction. The deltaR(CT) for a perfect duplex was 76(12) omega.cm(2), whereas a mismatch in the middle of the sequence yielded a deltaR(CT) value of 30(15) omega.cm(2). The detection limit was measured and the impedance methodology reliably detected single DNA base pair mismatches at concentrations as low as 100 pM.     

Ferrocene–Aspartate Dendrimers: Conformational Analysis and Electrochemical Studies

The syntheses of dendrimers based on aspartic acid (Asp) from generation 1 to generation 4 (G1 → G4) are reported. The ferrocene (Fc) conjugates of Asp dendrimers are synthesized. The solution structure of the monosubstituted Fc conjugates (FcG n) and the disubstituted Fc conjugates (Fc[G n ] ₂ ), n = 1–3, is studied using spectroscopic techniques. The structural analyses display the Fc core “wired” to the dendrimer shells via a net of H-bonds. Consequently, the conjugates exhibit higher heterogeneous electron transfer rate compared to the Fc glutamate analogues. FcG2 exhibits an unusual β-reverse turn structure in solution.     

Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules

β-Amyloid 42 (Aβ42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the Aβ42 aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used α-hemolysin (α-HL) pores to probe the different aggregation transition of Aβ42 in the presence of β-cyclodextrin (β-CD), a promoter of Aβ42 aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that β-CD and CR have opposite effects on the aggregation of Aβ42. Translocation events of the monomeric Aβ42 peptide were significantly lower in amplitude currents than protofilaments, and protofilaments were captured in the α-HL nanopore with a longer duration time. CR binds to Aβ42 and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, β-CD promotes the aggregation of Aβ42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological α-HL nanopore.     

Tobacco-related instruction in undergraduate nursing education in Illinois

Tobacco use is responsible for more deaths in the United States than any other factor. Nurses are in a unique position to convey life-saving messages to clients regarding tobacco use. To gauge the type and extent of tobacco-related background knowledge acquired by nurses in the course of their education, the Nurses' Committee of the Illinois Division of the American Cancer Society (ACS) surveyed 70 nursing programs in the state of Illinois. The number of lecture hours spent on tobacco-related issues was greater in LPN programs than in either associate or baccalaureate degree programs, and instruction was scattered throughout the curriculum of each program. Most schools reported heavy reliance on adult medical-surgical textbooks to convey tobacco-related content. The most recent editions of the textbooks used by the schools were reviewed, and they also were found to adopt a scattered approach, with a disappointing lack of depth regarding the hazards of tobacco. It is recommended a single course be identified as responsible for relaying tobacco-related content and information supplied by general medical-surgical textbooks be supplemented by materials drawn from other sources.     

Diffusion measurements on a liquid monotectic alloy PbGa using the shear cell technique under µg in the foton-M2 mission and under 1G

Diffusion experiments of a liquid monotectic alloy PbGa were performed under 1g-conditions at 623, 773 and 903K, and under µg-conditions at 903K. As a measurement tool the shear cell specially designed for Russian satellite Foton missions within the AGAT-furnace was used to have a homogenization time before the diffusion and to avoid the influence of decomposition into two liquid phases during cooling-down. The experiment type was diffusion from a thick layer of PbGa5at% into pure Pb. The liquid sample in the capillary was pressurized using a reservoir system in order to minimize Marangoni convection. In 1g-experiments the diffusion axis was arranged vertically and the sample was set such that the density increases monotonously parallel to the gravity vector in order to suppress buoyancy convection. Four experiments were performed simultaneously for each set-up. The µg-experiment was performed in the AGAT facility during the Foton-M2 mission (June 2005) where one capillary was assigned for the PbGa-Pb experiment (PbGa was containing an enriched Pb-isotope tracer). The concentration profiles were obtained by AAS (1g) and by ICP-MS (µg). The diffusion coefficients were evaluated by fitting with the thick layer solution. For the evaluation a correction method was used for the shear convection and the averaging effect inside each cell. As a result, the obtained concentration curves agreed well with the fitting function. The reproducibility of the diffusion coefficients among four parallel 1g-experiments was good with a standard deviation among four capillaries smaller than 5.5% including the standard temperature deviation. The diffusion coefficients agreed well between 1g- and µg-experiments. The temperature dependence of the diffusion coefficients could be fitted well to a power law with an exponent about 2.4. From these results we conclude that the 1g-experimental method in this study for diffusion measurement is effective also for monotectic systems.     

Shear cell development for diffusion experiments in FOTON-Satellite missions and on the ground with consideration of shear-induced convection

A shear cell technique was developed to obtain exact diffusion data. The shear cell in this study was designed for the utilization under μg-conditions, especially in the FOTON-M2 mission, but also under 1g-conditions. To minimize the influence of the shear convection, the cell size, the rotation system and the speed of the discs were optimized. To minimize free surfaces, which can cause Marangoni convection, a reservoir system providing pressure on the liquid was introduced. Using this FOTON shear cell we performed short-time diffusion experiments in the In-Sn system in a parabolic flight and under 1g conditions to investigate the influence of the shear convection quantitatively. As a result, the influence of the shear convection was so small that the mean square diffusion depth caused by the shear convection was in the order of10^{? 7}m², which is smaller than 1% of the typical value X _diff ² ≈ 10^{? 4}m² in a standard diffusion experiment using the FOTON shear cell. By using this result a correction method for the evaluation of the diffusion coefficient was established. In several ground experiments, the FOTON shear cell showed the same diffusion coefficients as from μg reference experiments within the range of errors and no obvious indication of Marangoni convection was detected. From these results we confirmed that the FOTON shear cell can be applied to μg-experiments and ground-based experiments as well.     

Surface studies of aminoferrocene derivatives on gold: electrochemical sensors for chemical warfare agents

The cystamine conjugate [(BocNH)Fc(CO)CSA]2 was prepared by coupling cystamine with the N-protected ferrocene amino acid derivative BocHN-Fc-COOH and was fully characterized by spectroscopic methods and by single-crystal X-ray diffraction. The cystamine conjugate forms films on gold substrates, which upon deprotection of the amino group, react with chemical warfare agent (CWA) mimics, upon which the redox properties of the Fc group are affected significantly. Cyclic voltammetry shows 50(5) mV anodic shifts of the Fc redox potentials after exposure to EtSCH2CH2Cl, a simulant for sulfur mustard HD (MA), and (NC)(EtO)2P(O), a simulant for nerve agent Tabun (NA). Exposure to MA and NA causes an increase in 2.3 and 4.5 ng mass, respectively, in QCM which indicates ca. 70% efficiency in Boc-deprotection. Ellipsometry measured a film thickness increase from 6(+/-1) A for the deprotected film to 10(+/-4) A for the film modified with MA and to 7(+/-2) A for the film modified with NA. AFM measurements show changes in the thickness and morphology of the film after reaction with MA and NA. The surfaces were analyzed by X-ray photoelectron spectroscopy (XPS) and clearly show the attachment of the cystamine conjugate on the surface and its reaction with CWA mimics.     

Peptide biosensors for the electrochemical measurement of protein kinase activity

The kinase activities are elucidated using the novel redox-active cosubstrate adenosine 5'-[gamma-ferrocene] triphosphate (Fc-ATP), which enables the kinase-catalyzed transfer of a redox active gamma-phosphate-Fc to a hydroxyamino acid. In this report, a versatile electrochemical biosensor is developed for monitoring the activity and inhibition of a serine/threonine kinase, casein kinase 2 (CK2), and protein tyrosine kinases, Abl1-T315I and HER2, in buffered solutions and in cell lysates. The method is based on the labeling of a specific phosphorylation event with Fc, followed by electrochemical detection. The electrochemical response obtained from the "ferrocenylated" peptides enables monitoring the activity of the kinase and its substrate, as well as the inhibition of small molecule inhibitors on protein phosphorylation. Kinetic information was extracted from the electrochemical measurements for the determination of K(m) and V(m) values, which were in agreement with those previously reported. Kinase reactions were also performed in the presence of well-defined inhibitors of CK2, 4,5,6,7-tetrabromo-2-azabenzimidazole, 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole, and E-3-(2,3,4,5-tetrabromophenyl)acrylic acid as well as the nonspecific kinase inhibitors, staurosporine and N-benzoylstaurosporine. On the basis of the dependency of the Fc signal on inhibitor concentration, K(i) of the inhibitors was estimated, which were also in agreement with the literature values. The performance of the biosensor was optimized including the kinase reaction, incubation with Fc-ATP, and the small molecule inhibitors. Peptide modified electrochemical biosensors are promising candidates for cost-effective in vitro kinase activity and inhibitor screening assays.