Triply Bonded Pancake π-Dimers Stabilized by Tetravalent Actinides.

Aromatic π-stacking is a weakly attractive, noncovalent interaction often found in biological macromolecules and synthetic supramolecular chemistry. The weak nondirectional nature of π-stacking can present challenges in the design of materials owing to their weak, nondirectional nature. However, when aromatic π-systems contain an unpaired electron, stronger attraction involving face-to-face π-orbital overlap is possible, resulting in covalent so-called "pancake" bonds. Two-electron, multicenter single pancake bonds are well known, whereas four-electron double pancake bonds are rare. Higher-order pancake bonds have been predicted, but experimental systems are unknown. Here, we show that six-electron triple pancake bonds can be synthesized by a 3-fold reduction of hexaazatrinaphthylene (HAN) and subsequent stacking of the [HAN]3- triradicals. Our analysis reveals a multicenter covalent triple pancake bond consisting of a σ-orbital and two equivalent π-orbitals. An electrostatic stabilizing role is established for the tetravalent thorium and uranium ions in these systems. We also show that the electronic absorption spectrum of the triple pancake bonds closely matches computational predictions, providing experimental verification of these unique interactions. The discovery of conductivity in thin films of triply bonded π-dimers presents new opportunities for the discovery of single-component molecular conductors and other spin-based molecular materials.

Bimetallic Synergy Enables Silole Insertion into THF and the Synthesis of Erbium Single-Molecule Magnets.

The potassium silole K2 [SiC4 -2,5-(SiMe3 )2 -3,4-Ph2 ] reacts with [M(η8 -COT)(THF)4 ][BPh4 ] (M=Er, Y; COT=cyclo-octatetraenyl) in THF to give products that feature unprecedented insertion of the nucleophilic silicon centre into a carbon-oxygen bond of THF. The structure of the major product, [(µ-η8 : η8 -COT)M(µ-L1 )K]∞ (1M ), consists of polymeric chains of sandwich complexes, where the spiro-bicyclic silapyran ligand [C4 H8 OSiC4 (SiMe3 )2 Ph2 ]2- (L1 ) coordinates to potassium via the oxygen. The minor product [(µ-η8 : η8 -COT)M(µ-L1 )K(THF)]2 (2M ) features coordination of the silapyran to the rare-earth metal. In forming 1M and 2M , silole insertion into THF only occurs in the presence of potassium and the rare-earth metal, highlighting the importance of bimetallic synergy. The lower nucleophilicity of germanium(II) leads to contrasting reactivity of the potassium germole K2 [GeC4 -2,5-(SiMe3 )2 -3,4-Me2 ] towards [M(η8 -COT)(THF)4 ][BPh4 ], with intact transfer of the germole occurring to give the coordination polymers [{η5 -GeC4 (SiMe3 )2 Me2 }M(η8 -COT)K]∞ (3M ). Despite the differences in reactivity induced by the group 14 heteroatom, the single-molecule magnet properties of 1Er , 2Er and 3Er are similar, with thermally activated relaxation occurring via the first-excited Kramers doublet, subject to effective energy barriers of 122, 80 and 91 cm-1 , respectively. Compound 1Er is also analysed by high-frequency dynamic magnetic susceptibility measurements up to 106  Hz.

What defines a chemokine? - The curious case of CXCL17.

Chemotactic cytokines (chemokines) are a group of around 40 small proteins which share a similar protein fold and are well known for their ability to direct the migration of leukocytes to a variety of tissue locations. CXCL17 was the last member of the chemokine family to be assigned and was admitted to the family based on theoretical modelling of the CXCL17 structure and chemotactic activity for monocytes and dendritic cells. Of Interest, CXCL17 expression appears to be restricted to mucosal tissues such as the tongue, stomach and lung, suggestive of specific roles at these locations. A putative CXCL17 receptor, GPR35 was reportedly identified and mice deficient in CXCL17 were generated and characterised. More recently, however, some apparent contradictions regarding aspects of CXCL17 biology have been raised by ourselves and others. Notably, GPR35 appears to be a receptor for the serotonin metabolite 5-hydroxyindoleacetic acid rather than for CXCL17 and modelling of CXCL17 using a variety of platforms fails to identify a chemokine-like fold. In this article, we summarize the discovery of CXCL17 and discuss key papers describing the subsequent characterisation of this protein. Ultimately, we pose the question, 'What defines a chemokine?' (185 words).

Identification of Oxidation State +1 in a Molecular Uranium Complex.

The concept of oxidation state plays a fundamentally important role in defining the chemistry of the elements. In the f block of the periodic table, well-known oxidation states in compounds of the lanthanides include 0, +2, +3 and +4, and oxidation states for the actinides range from +7 to +2. Oxidation state +1 is conspicuous by its absence from the f-block elements. Here we show that the uranium(II) metallocene [U(η5-C5iPr5)2] and the uranium(III) metallocene [IU(η5-C5iPr5)2] can be reduced by potassium graphite in the presence of 2.2.2-cryptand to the uranium(I) metallocene [U(η5-C5iPr5)2]- (1) (C5iPr5 = pentaisopropylcyclopentadienyl) as the salt of [K(2.2.2-cryptand)]+. An X-ray crystallographic study revealed that 1 has a bent metallocene structure, and theoretical studies and magnetic measurements confirmed that the electronic ground state of uranium(I) adopts a 5f3(7s/6dz2)1(6dx2-y2/6dxy)1 configuration. The metal-ligand bonding in 1 consists of contributions from uranium 5f, 6d, and 7s orbitals, with the 6d orbitals engaging in weak but non-negligible covalent interactions. Identification of the oxidation state +1 for uranium expands the range of isolable oxidation states for the f-block elements and potentially signposts a synthetic route to this elusive species for other actinides and the lanthanides.

Radio-Frequency Manipulation of State Populations in an Entangled Fluorine-Muon-Fluorine System.

Entangled spin states are created by implanting muons into single-crystal LiY_{0.95}Ho_{0.05}F_{4} to form a cluster of correlated, dipole-coupled local magnetic moments. The resulting states have well-defined energy levels allowing experimental manipulation of the state populations by electromagnetic excitation. Experimental control of the evolution of the muon spin polarization is demonstrated through application of continuous, radio-frequency electromagnetic excitation fields. A semiclassical model of quantum, dipole-coupled spins interacting with a classical, oscillating magnetic field accounts for the muon spin evolution. On application of the excitation field, this model shows how changes in the state populations lead to the experimentally observed effects, thus enabling a spectroscopic probe of entangled spin states with muons.

Discovery of a Dysprosium Metallocene Single-Molecule Magnet with Two High-Temperature Orbach Processes.

Magnetic bistability in single-molecule magnets (SMMs) is a potential basis for new types of nanoscale information storage material. The standard model for thermally activated relaxation of the magnetization in SMMs is based on the occurrence of a single Orbach process. Here, we show that incorporating a phosphorus atom into the framework of the dysprosium metallocene [(CpiPr5)Dy(CpPEt4)]+[B(C6F5)4]- (CpiPr5 is penta-isopropylcyclopentadienyl, CpPEt4 is tetraethylphospholyl) leads to the occurrence of two distinct high-temperature Orbach processes, with energy barriers of 1410(10) and 747(7) cm-1, respectively. These barriers provide experimental evidence for two different spin-phonon coupling regimes, which we explain with the aid of ab initio calculations. The strong and highly axial crystal field in this SMM also allows magnetic hysteresis to be observed up to 70 K, using a scan rate of 25 Oe s-1. In characterizing this SMM, we show that a conventional Debye model and consideration of rotational contributions to the spin-phonon interaction are insufficient to explain the observed phenomena.

Proximity-Induced Odd-Frequency Superconductivity in a Topological Insulator.

At an interface between a topological insulator (TI) and a conventional superconductor (SC), superconductivity has been predicted to change dramatically and exhibit novel correlations. In particular, the induced superconductivity by an s-wave SC in a TI can develop an order parameter with a p-wave component. Here we present experimental evidence for an unexpected proximity-induced novel superconducting state in a thin layer of the prototypical TI, Bi_{2}Se_{3} proximity coupled to Nb. From depth-resolved magnetic field measurements below the superconducting transition temperature of Nb, we observe a local enhancement of the magnetic field in Bi_{2}Se_{3} that exceeds the externally applied field, thus supporting the existence of an intrinsic paramagnetic Meissner effect arising from an odd-frequency superconducting state. Our experimental results are complemented by theoretical calculations supporting the appearance of such a component at the interface which extends into the TI. This state is topologically distinct from the conventional Bardeen-Cooper-Schrieffer state it originates from. To the best of our knowledge, these findings present a first observation of bulk odd-frequency superconductivity in a TI. We thus reaffirm the potential of the TI-SC interface as a versatile platform to produce novel superconducting states.

Extreme Fermi Surface Smearing in a Maximally Disordered Concentrated Solid Solution.

We show that the Fermi surface can survive the presence of extreme compositional disorder in the equiatomic alloy Ni_{0.25}Fe_{0.25}Co_{0.25}Cr_{0.25}. Our high-resolution Compton scattering experiments reveal a Fermi surface which is smeared across a significant fraction of the Brillouin zone (up to 40% of 2π/a). The extent of this smearing and its variation on and between different sheets of the Fermi surface have been determined, and estimates of the electron mean free path and residual resistivity have been made by connecting this smearing with the coherence length of the quasiparticle states.

Rare-Earth Cyclobutadienyl Sandwich Complexes: Synthesis, Structure and Dynamic Magnetic Properties.

The potassium cyclobutadienyl [K2 {η4 -C4 (SiMe3 )4 }] (1) reacts with MCl3 (THF)3.5 (M=Y, Dy) to give the first rare-earth cyclobutadienyl complexes, that is, the complex anions [M{η4 -C4 (SiMe3 )4 }{η4 -C4 (SiMe3 )3 -κ-(CH2 SiMe2 }]2- , (2M ), as their dipotassium salts. The tuck-in alkyl ligand in 2M is thought to form through deprotonation of the "squarocene" complexes [M{η4 -C4 (SiMe3 )4 }2 ]- by 1. Complex 2Dy is a single-molecule magnet, but with prominent quantum tunneling. An anisotropy barrier of 323(22) cm-1 was determined for 2Dy in an applied field of 1 kOe, and magnetic hysteresis loops were observed up to 7 K.

Superconductivity in planarised nanocrystalline diamond films.

Chemical vapour deposition (CVD) grown boron-doped nanocrystalline diamond (B-NCD) is an attractive material for the fabrication of high frequency superconducting nanoelectromechanical systems (NEMS) due to its high Young's modulus. The as-grown films have a surface roughness that increases with film thickness due to the columnar growth mechanism. To reduce intrinsic losses in B-NCD NEMS it is crucial to correct for this surface roughness by polishing. In this paper, in contrast to conventional polishing, it is demonstrated that the root-mean-square (RMS) roughness of a 520 nm thick B-NCD film can be reduced by chemical mechanical polishing (CMP) from 44.0 nm to 1.5 nm in 14 hours without damaging the sample or introducing significant changes to the superconducting transition temperature, [Formula: see text], thus enabling the use of B-NCD films in the fabrication of high quality superconducting NEMS.

Reactive surface area of the Li(x)(Co(1/3)Ni(1/3)Mn(1/3))O2 electrode determined by µ(+)SR and electrochemical measurements.

The self-diffusion coefficient of Li(+) ions (D(Li)) in the positive electrode material Li(x)(Co(1/3)Ni(1/3)Mn(1/3))O2 has been estimated by muon-spin relaxation (µ(+)SR) using powder samples with x = 1-0.49, which were prepared by an electrochemical reaction in a Li-ion battery. Here, since the implanted muons sense a slight change in the internal magnetic field due to Li-diffusion, µ(+)SR provides an intrinsic D(Li) through the temperature dependence of the nuclear field fluctuation rate (ν) [Sugiyama et al., Phys. Rev. Lett., 2009, 103, 147601]. Both D(Li) at 300 K and activation energy (E(a)) were estimated to be ∼2.9 × 10(-12) cm(2) s(-1) and 0.074 eV for the x = 1 sample, ∼11.0 × 10(-12) cm(2) s(-1) and 0.097 eV for x = 0.70, and ∼8.9 × 10(-12) cm(2) s(-1) and 0.062 eV for x = 0.49, assuming that the diffusing Li(+) ions mainly jump from a regular occupied site to a regular vacant site. The estimated D(Li) was smaller by roughly one order of magnitude than those for Li(x)CoO2 in the whole x range measured. Furthermore, by making comparison with D(Li) obtained by electrochemical measurements, the reactive surface area of the Li(x)(Co(1/3)Ni(1/3)Mn(1/3))O2 electrode in a liquid electrolyte was found to strongly depend on x particularly at x > 0.8.

CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling.

Introduction: CXCL17 is a mucosally secreted protein, and the most recently identified human chemokine, an assignment based on protein fold prediction and chemotactic activity for leukocytes. However, these credentials have been the subject of much recent discussion and no experimental evidence has been presented regarding the definitive structure of CXCL17. In this study, we evaluated the structural and chemoattractant credentials of CXCL17 to better characterize this molecule, and gain deeper insights into its functional role as a glycosaminoglycan (GAG) binding protein. Methods: In the absence of structural information, in silico modeling techniques assessed the likelihood of CXCL17 adopting a chemokine fold. Recombinant CXCL17 was synthesized in mammalian and prokaryotic systems. Modified Boyden chamber and real-time chemotaxis assays assessed the ability of CXCL17 to promote chemotaxis of murine splenocytes, human neutrophils, and CXCR1 transfectants. The efficacy of CXCL17 binding to GAGs was quantified with solid-phase assays and bio-layer interferometry techniques. Results: All modeling efforts failed to support classification of CXCL17 as a chemokine based on its predicted conformation. Recombinant CXCL17 was observed to dimerize as a function of concentration, a characteristic of several chemokines. Contrary to a previous report, CXCL17 was not chemotactic for murine splenocytes, although it was a low-potency chemoattractant for human neutrophils at micromolar concentrations, several orders of magnitude higher than those required for CXCL8. As anticipated owing to its highly basic nature, CXCL17 bound to GAGs robustly, with key C-terminal motifs implicated in this process. While inactive via CXCR1, CXCL17 was found to inhibit CXCR1-mediated chemotaxis of transfectants to CXCL8 in a dose-dependent manner. Discussion: In summary, despite finding little evidence for chemokine-like structure and function, CXCL17 readily bound GAGs, and could modulate chemotactic responses to another chemokine in vitro. We postulate that such modulation is a consequence of superior GAG binding, and that C-terminal fragments of CXCL17 may serve as prototypic inhibitors of chemokine function.

The protease associated (PA) domain in ScpA from Streptococcus pyogenes plays a role in substrate recruitment.

Annually, over 18 million disease cases and half a million deaths worldwide are estimated to be caused by Group A Streptococcus. ScpA (or C5a peptidase) is a well characterised member of the cell enveleope protease family, which possess a S8 subtilisin-like catalytic domain and a shared multi-domain architecture. ScpA cleaves complement factors C5a and C3a, impairing the function of these critical anaphylatoxins and disrupts complement-mediated innate immunity. Although the high resolution structure of ScpA is known, the details of how it recognises its substrate are only just emerging. Previous studies have identified a distant exosite on the 2nd fibronectin domain that plays an important role in recruitment via an interaction with the substrate core. Here, using a combination of solution NMR spectroscopy, mutagenesis with functional assays and computational approaches we identify a second exosite within the protease-associated (PA) domain. We propose a model in which the PA domain assists optimal delivery of the substrate's C terminus to the active site for cleavage.

The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System.

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as Streptococcus pyogenes CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.

A highly efficient method for the production and purification of recombinant human CXCL8.

Chemokines play diverse and fundamental roles in the immune system and human disease, which has prompted their structural and functional characterisation. Production of recombinant chemokines that are folded and bioactive is vital to their study but is limited by the stringent requirements of a native N-terminus for receptor activation and correct disulphide bonding required to stabilise the chemokine fold. Even when expressed as fusion proteins, overexpression of chemokines in E. coli tends to result in the formation of inclusion bodies, generating the additional steps of solubilisation and refolding. Here we present a novel method for producing soluble chemokines in relatively large amounts via a simple two-step purification procedure with no requirements for refolding. CXCL8 produced by this method has the correct chemokine fold as determined by NMR spectroscopy and in chemotaxis assays was indistinguishable from commercially available chemokines. We believe that this protocol significantly streamlines the generation of recombinant chemokines.

Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix.

The identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion of exons from mature mRNA. However, mis-regulation of this process is associated with most human diseases. Here, we examine the impact of post-transcriptional processing on extracellular matrix function, focusing on the complex alternative splicing patterns of tenascin-C, a molecule that can exist in as many as 500 different isoforms. We demonstrate that the pro-inflammatory activity of this endogenous innate immune trigger is controlled by inclusion or exclusion of a novel immunomodulatory site located within domains AD2AD1, identifying this as a mechanism that prevents unnecessary inflammation in healthy tissues but enables rapid immune cell mobilization and activation upon tissue damage, and defining how this goes awry in autoimmune disease.

Transverse and longitudinal spin-fluctuations in INVAR Fe0.65Ni0.35.

The presence of spin-fluctuations deep within the ordered state of ferromagnetic [Formula: see text] alloy [Formula: see text] has long been suspected but seldom directly observed. Inhomogeneities of one type or another have been cited as important in stabilizing [Formula: see text] behaviour-either longitudinal spin-fluctuations associated with the [Formula: see text]-state (local environment) model or transverse magnetisation arising from non-collinear spin structures. In this study we employ small-angle neutron scattering with neutron polarization analysis to distinguish between the two possibilities. Surprisingly we in fact find evidence of dominant but uncorrelated longitudinal spin-fluctuations coexisting with transverse magnetisation which exists in short-range clusters of size ~[Formula: see text]. This finding supports recent first principles calculations of [Formula: see text] in which both longitudinal spin-fluctuations and magnetic short-range order are identified as important ingredients in reproducing the equilibrium [Formula: see text] lattice.

How to detect and purify tenascin-C.

The extracellular matrix molecule tenascin-C (TNC) was discovered over 30 years ago, and its tightly regulated pattern of expression since sparked keen interest in the scientific community. In adult tissues, TNC expression is restricted to specific niches and areas of active remodeling or high mechanical strain. However, while most healthy tissues contain little TNC, its transient expression upon cellular stress or tissue injury helps to mediate repair and restore homeostasis. Persistent expression of TNC is associated with chronic inflammation, fibrosis, and cancer, where methods for its detection are emerging as a reliable means to predict disease onset, prognosis, and response to treatment. Because studying the expression of this large matrix molecule is not always straightforward, here we describe basic techniques to examine tissue levels of TNC mRNA and protein. We also describe methods for purifying recombinant TNC, knocking down its expression, and creating cell-derived matrices with or without TNC within.

Vacancies, disorder-induced smearing of the electronic structure, and its implications for the superconductivity of anti-perovskite MgC0.93Ni2.85.

The anti-perovskite superconductor MgC0.93Ni2.85 was studied using high-resolution x-ray Compton scattering combined with electronic structure calculations. Compton scattering measurements were used to determine experimentally a Fermi surface that showed good agreement with that of our supercell calculations, establishing the presence of the predicted hole and electron Fermi surface sheets. Our calculations indicate that the Fermi surface is smeared by the disorder due to the presence of vacancies on the C and Ni sites, but does not drastically change shape. The 20% reduction in the Fermi level density-of-states would lead to a significant (~70%) suppression of the superconducting T c for pair-forming electron-phonon coupling. However, we ascribe the observed much smaller T c reduction at our composition (compared to the stoichiometric compound) to the suppression of pair-breaking spin fluctuations.

Tenascin-C: Form versus function.

Tenascin-C is a large, multimodular, extracellular matrix glycoprotein that exhibits a very restricted pattern of expression but an enormously diverse range of functions. Here, we discuss the importance of deciphering the expression pattern of, and effects mediated by, different forms of this molecule in order to fully understand tenascin-C biology. We focus on both post transcriptional and post translational events such as splicing, glycosylation, assembly into a 3D matrix and proteolytic cleavage, highlighting how these modifications are key to defining tenascin-C function.