Anion exchange in the channels of a robust alkaline earth sulfonate coordination network

The barium sulfonate network presented herein, [[Ba2(L)(H2O)5]Cl]infinity (1), represents the first metal sulfonate compound to possess a cationic framework. The network is layered with channels between pillaring ligands in which chloride ions reside. Compound 1 contracts slightly upon dehydration but retains its overall structural motif to 420 degrees C. Significantly, the chloride ions of the structure can be exchanged in 80% yield for fluoride ions in a facile manner. This exchange is quantified by elemental analyses, gravimetric determination, and 19F NMR spectroscopy. Confirmation of retention of structure is provided by standardized powder X-ray diffraction experiments. This last point is notable as the F-analogue of the structure is not attainable by a direct synthesis. These results illustrate one of the hallmark features of supramolecular chemistry, that a robust and functional framework can result through cooperative interactions between more weakly interacting units.     

The bicyclic n,n'-diacylaminal: a new motif for molecular self-assembly

A cage-shaped N,N'-diacylaminal crystallizes from some aromatic solvents as "supramolecular chair cyclohexanes", squat cylindrical hexamers with approximate D3d symmetry containing two arene molecules, and from other aromatic and nonaromatic solvents as infinite tapes. A homologous diacylaminal crystallizes only as an infinite tape. The hexamers represent the first examples of cyclic hexamers held together by %@mt;sys@%%@bold@%R%@rsf@%%@sx@%2%@be@%2%@sxx@%%@fn;(;vis;full;auto@%8%@fnx;);vis;full@%-type%@mx@% hydrogen bonds in which the hydrogen-bonded atoms are not coplanar. The diacylaminal represents a new supramolecular synthon, one perhaps more suited to the design of three-dimensional architectures.     

Polar effects in nitride coupling reactions

The nucleophilic molybdenum nitride (Et(2)NCS(2))(3)MoN (1) reacts with the electrophilic osmium nitride complex TpOsNCl(2) (2, Tp = hydrotris(1-pyrazolyl)borate) to produce molecular nitrogen. Reaction of 1 at the nitride is accompanied by a substantial amount of reaction at a sulfur atom of the dithiocarbamate ligand, forming the osmium thionitrosyl complex TpOs(NS)Cl(2) (4). Labeling experiments establish that the N(2) produced comes specifically (>96%) from mixed-metal (molybdenum-osmium) coupling. The major transition-metal-containing product of the reaction is the mu-nitrido complex TpOsCl(2)(mu-N)Mo(S(2)CNEt(2))(3) (3), where the bridging nitride derives primarily (82%) from the osmium nitride 2. The mu-nitrido complex 3 has been characterized crystallographically, and shows a nitride bridge that is very asymmetric (Mo-N = 1.721(3) A, Os-N = 1.906(3) A), with less multiple bonding toward osmium and more toward molybdenum. Heterometallic coupling is much faster than either homometallic coupling reaction, in particular the osmium-osmium coupling, despite the greater oxidizing power of osmium over molybdenum. The origin and implications of this kinetic effect on nitride coupling and dinitrogen cleavage are discussed.     

Precipitation of inorganic salts inside hollow micrometer-sized polyelectrolyte shells

Hollow polymer shells formed by layer-by-layer adsorption of oppositely charged polyelectrolytes onto micrometer-sized colloidal particles with subsequent decomposition of the colloidal core were employed as a model system for the study of inorganic crystallization reactions in restricted volumes. The size-selective permeability of shells is used for spatially controlling the precipitation of inorganic salts CaCO3 and BaCO3 into the shell interior. Outside the shells the precipitation was suppressed by the polymers, which are unable to penetrate the shell wall. The precipitates were studied by scanning electron microscopy and atomic force microscopy. The fundamental and applied aspects of research on spatially confined synthesis of inorganic particles are under discussion.     

Novel stereocontrolled addition of allylmetal reagents to alpha-imino esters: efficient synthesis of chiral tetrahydroquinoline derivatives

To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.     

Functionalized heteropolyanions: high-valent metal nitrido fragments incorporated into a Keggin polyoxometalate structure

Three examples of nitrido-functionalized polyoxometalate species are reported, namely (n-Bu4N)4[PW11O39(OsN)] (1), (n-Bu4N)4[PW11O39(ReN)] (2), and (n-Bu4N)3[PW11O39(ReN)] (3), which feature the incorporation of [OsVI identical to N]3+, [ReVI identical to N]3+ and [ReVII identical to N]4+ fragments, respectively, into the framework of a Keggin-type heteropolyanion.     

Diffraction-limited, 300-kW peak-power pulses from a coiled multimode fiber amplifier

We report a multimode, double-clad, Yb-doped fiber amplifier that produces diffraction-limited, 0.8-ns pulses with energies of 255 muJ and peak powers in excess of 300 kW at a repetition rate of ~8 kHz . Single-transverse-mode operation was obtained by bend-loss-induced mode filtering of the gain fiber.     

Towards a new age of virtual ADME/TOX and multidimensional drug discovery

With the continual pressure to ensure follow-up molecules to billion dollar blockbuster drugs, there is a hurdle in profitability and growth for pharmaceutical companies in the next decades. With each success and failure we increasingly appreciate that a key to the success of synthesized molecules through the research and development process is the possession of drug-like properties. These properties include an adequate bioactivity as well as adequate solubility, an ability to cross critical membranes (intestinal and sometimes blood-brain barrier), reasonable metabolic stability and of course safety in humans. Dependent on the therapeutic area being investigated it might also be desirable to avoid certain enzymes or transporters to circumvent potential drug-drug interactions. It may also be important to limit the induction of these same proteins that can result in further toxicities. We have clearly moved the assessment of in vitro absorption, distribution, metabolism, excretion and toxicity (ADME/TOX) parameters much earlier in the discovery organization than a decade ago with the inclusion of higher throughput systems. We are also now faced with huge amounts of ADME/TOX data for each molecule that need interpretation and also provide a valuable resource for generating predictive computational models for future drug discovery. The present review aims to show what tools exist today for visualizing and modeling ADME/TOX data, what tools need to be developed, and how both the present and future tools are valuable for virtual filtering using ADME/TOX and bioactivity properties in parallel as a viable addition to present practices.     

MMP-28 as a regulator of myelination

Background  

Matrix metalloproteinase-28 (MMP-28) is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment.     

Calcium transients in astrocyte endfeet cause cerebrovascular constrictions

Cerebral blood flow (CBF) is coupled to neuronal activity and is imaged in vivo to map brain activation. CBF is also modified by afferent projection fibres that release vasoactive neurotransmitters in the perivascular region, principally on the astrocyte endfeet that outline cerebral blood vessels. However, the role of astrocytes in the regulation of cerebrovascular tone remains uncertain. Here we determine the impact of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in astrocytes on the diameter of small arterioles by using two-photon Ca(2+) uncaging to increase [Ca(2+)](i). Vascular constrictions occurred when Ca(2+) waves evoked by uncaging propagated into the astrocyte endfeet and caused large increases in [Ca(2+)](i). The vasoactive neurotransmitter noradrenaline increased [Ca(2+)](i) in the astrocyte endfeet, the peak of which preceded the onset of arteriole constriction. Depressing increases in astrocyte [Ca(2+)](i) with BAPTA inhibited the vascular constrictions in noradrenaline. We find that constrictions induced in the cerebrovasculature by increased [Ca(2+)](i) in astrocyte endfeet are generated through the phospholipase A(2)-arachidonic acid pathway and 20-hydroxyeicosatetraenoic acid production. Vasoconstriction by astrocytes is a previously unknown mechanism for the regulation of CBF.