Solution and solid-state structure of the anion [Ag(2)[closo-CB(11)H(12)](4)](2-)

Addition of the carbene 1,3-dimesitylimidazol-2-ylidene (IMes) to a toluene solution of Ag[closo-CB(11)H(12)] results in the formation of the complex [(IMes)(2)Ag](2)[Ag(2)[closo-CB(11)H(12)](4)], the anionic component of which contains two silver(I) centers bridged by two carboranes in addition to one terminally bound carborane on each metal, in the solid-state. Comparison of the observed (11)B[(1)H] NMR chemical shifts of [(IMes)(2)Ag](2)[Ag(2)[closo-CB(11)H(12)](4)] or Ag[closo-CB(11)H(12)] with [NBu(4)][closo-CB(11)H(12)] in CD(2)Cl(2) demonstrates that the silver ion interacts significantly with the cage in solution. Theoretical investigations using the ab initio/GIAO/NMR method of [closo-CB(11)H(12)](-) and Na[closo-CB(11)H(12)] as model geometries for the silver salts support experimental evidence for these Ag...[BH] interactions in solution.     

Synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphoric acid analogues as alternate substrates for methylerythritol phosphate synthase

[structure: see text] Four deoxyxylulose phosphate (DXP) analogues were synthesized and evaluated as substrates/inhibitors for methylerythritol phosphate (MEP) synthase. In analogues CF(3)-DXP (1), CF(2)-DXP (2), and CF-DXP (3), the three methyl hydrogens at C1 of DXP were sequentially replaced by fluorine. In the fourth analogue, Et-DXP (4), the methyl group in DXP was replaced by an ethyl moiety. Analogues 1, 2, and 4 were not substrates for MEP synthase under normal catalytic conditions and were instead modest inhibitors with IC(50) values of 2.0, 3.4, and 6.2 mM, respectively. In contrast, 3 was a good substrate (k(cat) = 38 s(-)(1), K(m) = 227 muM) with a turnover rate similar to that of the natural substrate. These results are consistent with a retro-aldol/aldol mechanism rather than an alpha-ketol rearrangement for the enzyme-catalyzed conversion of DXP to MEP.     

Copper(II) complexes of pyridyl-appended diazacycloalkanes: synthesis, characterization, and application to catalytic olefin aziridination

As part of an ongoing effort to rationally design new copper catalysts for olefin aziridination, a family of copper(II) complexes derived from new tetradentate macrocyclic ligands are synthesized, characterized both in the solid state and in solution, and screened for catalytic nitrene transfer reactivity with a representative set of olefins. The pyridylmethyl-appended diazacycloalkane ligands L6(py)2, L7(py)2, and L8(py)2 are prepared by alkylation of the appropriate diazacycloalkane (piperazine, homopiperazine, or diazacyclooctane) with picolyl chloride in the presence of triethylamine. The ligands are metalated with Cu(ClO4)(2).6H2O to provide the complexes [(L6(py)2)Cu(OClO3)]ClO4 (1), [(L7(py)2)Cu(OClO3)]ClO4 (2), and [(L8(py)2)Cu](ClO4)2 (3), which, after metathesis with NH4PF6 in CH3CN, afford [(L6(py)2)Cu(CH3CN)](PF6)2 (4), [(L7(py)2)Cu(CH3CN)](PF6)2 (5), and [(L8(py)2)Cu](PF6)2 (6). All six complexes are characterized by X-ray crystallography, which reveals that complexes supported by L6(py)2 and L7(py)2 (1, 2, 4, 5) adopt square-pyramidal geometries, while complexes 3 and 6, ligated by L8(py)2 feature tetracoordinate, distorted-square-planar copper ions. Tetragonal geometries in solution and d(x2 - y2), ground states are confirmed for the complexes by a combination of UV-visible and EPR spectroscopies. The divergent flexibility of the three supporting ligands influences the Cu(II)/Cu(I) redox potentials within the family, such that the complexes supported by the larger ligands L7(py)2 and L8(py)2 (5 and 6) exhibit quasi-reversible electron transfer processes (E1/2 approximately -0.2 V vs Ag/AgCl), while the complex supported by L6(py)2 (4), which imposes a rigid tetragonal geometry upon the central copper(II) ion, is irreversibly reduced in CH3CN solution. Complexes 4-6 are efficient catalysts (in 5 mol % amounts) for the aziridination of styrene with the iodinane PhINTs (in 80-90% yields vs PhINTs), while only 4 exhibits significant catalytic nitrene transfer reactivity with 1-hexene and cyclooctene.     

Hormone-induced modification of EGF receptor proteolysis in the induction of EGF action.

A proposal that EGF action is mediated through enhanced internalization of EGF receptors is modified to account for more recent evidence. EGF receptors turn over at a rapid rate, and the maintenance of a steady state of EGF receptors on the cell surface is provided through a rapid synthesis of EGF receptors, balancing their removal. This rapid turnover of unoccupied receptors may arise through their internalization and proteolysis in the lysosomes, in much the same way as receptors are internalized and degraded when exposed to EGF, which enhances internalization. This provides a dilemmma for the endocytic activation concept, since slight enhancement of receptor internalization gives rise to a strong hormone response. This problem may be solved by the observation that EGF induces a change in its receptor, exposing an otherwise unavailable site for proteolytic cleavage. This hormone-dependent modification of receptors may be the critical step in the induction of responses to EGF and other hormones that are internalized with their receptors. Both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are shown to down-regulate EGF receptors, though transiently, placing still more stringent requirements on the specificity by which hormones might act through endocytic activation of their receptors.     

A new method for the determination of the 34S/32S ratio of water-soluble sulphur in soil

A new method for the determination of the ³⁴S/³²S ratio of water-extractable sulphate in soil is described. Soils are extracted directly with deionized water, which is evaporated down. The remaining residue is then rehydrated and transferred to tin cups containing an adsorbent and mixed with an oxygen donor (V₂O₅). Samples are then analysed using a continuous flow isotope ratio mass spectrometer. The new method requires around 10?g soil per determination, compared to much larger amounts (up to kilograms) of soil required for the previous methods. Sample preparation and subsequent analysis is quick and efficient. The method is demonstrated using a number of soils collected from around the world to provide a range of determined δ³⁴S values. The δ³⁴S values of water-extractable sulphur were broadly similar to those of the soil total sulphur.     

Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period

ABSTRACT: BACKGROUND: The peri-adolescent period is a crucial developmental moment of transition from childhood to emergent adulthood. The present report analyses the differences in Power Spectrum (PS) of the Electroencephalogram (EEG) between late childhood (24 children between 8 and 13 years old) and young adulthood (24 young adults between 18 and 23 years old). RESULTS: The narrow band analysis of the Electroencephalogram was computed in the frequency range of 0--20 Hz. The analysis of mean and variance suggested that six frequency ranges presented a different rate of maturation at these ages, namely: low delta, delta-theta, low alpha, high alpha, low beta and high beta. For most of these bands the maturation seems to occur later in anterior sites than posterior sites. Correlational analysis showed a lower pattern of correlation between different frequencies in children than in young adults, suggesting a certain asynchrony in the maturation of different rhythms. The topographical analysis revealed similar topographies of the different rhythms in children and young adults. Principal Component Analysis (PCA) demonstrated the same internal structure for the Electroencephalogram of both age groups. Principal Component Analysis allowed to separate four subcomponents in the alpha range. All these subcomponents peaked at a lower frequency in children than in young adults. CONCLUSIONS: The present approaches complement and solve some of the incertitudes when the classical brain broad rhythm analysis is applied. Children have a higher absolute power than young adults for frequency ranges between 0-20 Hz, the correlation of Power Spectrum (PS) with age and the variance age comparison showed that there are six ranges of frequencies that can distinguish the level of EEG maturation in children and adults. The establishment of maturational order of different frequencies and its possible maturational interdependence would require a complete series including all the different ages.     

Ageing of surface treated thermoplastic polyolefins

Thermoplastic polyolefin panels were treated with a flame, flame & water, and accelerated thermo molecular adhesion process (ATmaP) treatment. XPS, contact angle and adhesion test (pull off) results were acquired over a one year period to determine the changes in the elemental composition, surface energy and adhesion strength respectively over time. All surface-treated thermoplastic polyolefin samples showed a sharp decline in adhesion strength up to an ageing period totalling 6 months. The decline in adhesion strength was correlated with a decline in the nitrogen-containing constituents and C–O functional groups at the surface and a decline in surface energy for the flame & water-treated sample. There was no significant change in adhesion strength for all samples for ageing periods greater than 6 months. ATmaP-treated thermoplastic polyolefin outperformed the other two surface treatments in adhesion strength tests due to ATmaP retaining nitrogen-based functional groups (mainly nitrogen oxides) over the year long study. This retention of functionality allowed for a slower ageing process for ATmaP-treated surfaces in comparison to the other surface treatments.     

Divergent Synthesis of Monosubstituted and Unsymmetrical 3,6‐Disubstituted Tetrazines from Carboxylic Ester Precursors

Since tetrazines are important tools to the field of bioorthogonal chemistry, there is a need for new approaches to synthesize unsymmetrical and 3‐monosubstituted tetrazines. Described here is a general, one‐pot method for converting (3‐methyloxetan‐3‐yl)methyl carboxylic esters into 3‐thiomethyltetrazines. These versatile intermediates were applied to the synthesis of unsymmetrical tetrazines through Pd‐catalyzed cross‐coupling and in the first catalytic thioether reduction to access monosubstituted tetrazines. This method enables the development of new tetrazine compounds possessing a favorable combination of kinetics, small size, and hydrophilicity. It was applied to a broad range of aliphatic and aromatic ester precursors and to the synthesis of heterocycles including BODIPY fluorophores and biotin. In addition, a series of tetrazine probes for monoacylglycerol lipase (MAGL) were synthesized and the most reactive one was applied to the labeling of endogenous MAGL in live cells.     

Derivative temporal clustering analysis: detecting prolonged neuronal activity

Temporal clustering analysis (TCA) and independent component analysis (ICA) are promising data-driven techniques in functional magnetic resonance imaging (fMRI) experiments to obtain brain activation maps in conditions with unknown temporal information regarding the neuronal activity. Although comparable to ICA in detecting transient neuronal activities, TCA fails to detect prolonged plateau brain activations. To eliminate this pitfall, a novel derivative TCA (DTCA) method was introduced and its algorithms with different subtraction intervals were tested on simulated data with a pattern of prolonged plateau brain activation. It was found that the best performance of DTCA method in generating functional maps could be obtained if the subtraction interval is equal to or larger than the length of the rising time of the fMRI response. The DTCA method and its theoretical predication were further investigated and validated using in vivo fMRI data sets. By removing the limitations in the previous TCA, DTCA has shown its powerful capability in detecting prolonged plateau neuronal activities.     

Mechanisms of sulfanyl (RS) migrations: synthesis of heterocycles

Thiiranium (episulfonium) ions had been acknowledged as reaction intermediates for many years, but it was not until 1977 that Nicolaou demonstrated systematically that these reactive heterocyclic cations could be trapped by carboxylic acids to give lactones. In the years that followed this report, extensive research greatly extended the scope of this reaction, particularly with regard to the methods for generating thiiranium ions, the types of nucleophiles that are compatible with this reaction, and the selectivity involved in the cyclization reactions. For many years we have been using thiiranium ions for the synthesis of saturated heterocycles. Whereas Nicolaou's method relied on electrophilic sulfenylation of alkenes, we have generated thiiranium ions by displacement of a leaving group with neighboring-group participation by a sulfanyl group. Many of the examples we have reported are of cyclizations that are reversible and so where two (and in some cases more) products can result, the outcome of the reactions provides fundamental information about the relative stability of different heterocyclic ring systems. This Review will begin with a brief introduction to sulfanyl participation as a method for generating thiiranium (and thiolanium) ions, and will go on to explore the idea of using sulfanyl migrations in synthesis. Initially, emphasis will be placed on mechanisms of [1,2] sulfanyl migrations: we will look specifically at [1,2] sulfanyl migrations (usually PhS) with elimination, substitution, and cyclization. Emphasis will then shift to the factors that affect the outcome of cyclization reactions. In particular, we will cover cyclizations with hydroxy nucleophiles and examine situations in which there are more than one hydroxy nucleophile present. We will also examine cyclizations with other nucleophiles, namely amines and sulfides. After our discussion of [1,2] sulfanyl migrations, we will look very briefly at the scope of [1,4] sulfanyl participation, before finally drawing up some guidelines that (we hope) will help other organic chemists take advantage of the rearrangement reactions that the sulfanyl group has to offer.