Spin-Crossover in Supramolecular Iron(II)-2,6-bis(1H-Pyrazol-1-yl)pyridine Complexes: Toward Spin-State Switchable Single-Molecule Junctions.

Spin-crossover (SCO) active iron(II) complexes are an integral class of switchable and bistable molecular materials. Spin-state switching properties of the SCO complexes have been studied in the bulk and single-molecule levels to progress toward fabricating molecule-based switching and memory elements. Supramolecular SCO complexes featuring anchoring groups for metallic electrodes, for example, gold (Au), are ideal candidates to study spin-state switching at the single-molecule level. In this study, we report on the spin-state switching characteristics of supramolecular iron(II) complexes 1 and 2 composed of functional 4-([2,2'-bithiophen]-5-ylethynyl)-2,6-di(1H-pyrazol-1-yl)pyridine (L1) and 4-(2-(5-(5-hexylthiophen-2-yl)thiophen-2-yl)ethynyl)-2,6-di(1H-pyrazol-1-yl)pyridine (L2) ligands, respectively. Density functional theory (DFT) studies revealed stretching-induced spin-state switching in a molecular junction composed of complex 1, taken as a representative example, and gold electrodes. Single-molecule conductance traces revealed the unfavorable orientation of the complexes in the junctions to demonstrate the spin-state dependence of the conductance.

NNC-Scorpionate Zirconium-Based Bicomponent Systems for the Efficient CO2 Fixation into a Variety of Cyclic Carbonates.

Two new derivatives of the bis(3,5-dimethylpyrazol-1-yl)methane modified by introduction of organosilyl groups on the central carbon atom, one of which bearing a chiral fragment, have been easily prepared. We verified the potential utility of these compounds through the reaction with [Zr(NMe2)4] for the preparation of novel zirconium complexes in which an ancillary bis(pyrazol-1-yl)methanide acts as a robust monoanionic tridentate scorpionate in a κ3-NNC chelating mode, forming strained four-membered heterometallacycles. These κ3-NNC-scorpionate zirconium amides were investigated as catalysts in combination with tetra-n-butylammonium bromide as cocatalyst for CO2 fixation into five-membered cyclic carbonate products. The study has led to the development of an efficient zirconium-based bicomponent system for the selective cycloaddition reaction of CO2 with epoxides. Kinetics investigations confirmed apparent first-order dependence on the catalyst and cocatalyst concentrations. In addition, this system displays very broad substrate scope, including mono- and disubstituted substrates, as well as the challenging biorenewable terpene derived limonene oxide, under mild and solvent-free conditions.

Siesta: Recent developments and applications.

A review of the present status, recent enhancements, and applicability of the Siesta program is presented. Since its debut in the mid-1990s, Siesta's flexibility, efficiency, and free distribution have given advanced materials simulation capabilities to many groups worldwide. The core methodological scheme of Siesta combines finite-support pseudo-atomic orbitals as basis sets, norm-conserving pseudopotentials, and a real-space grid for the representation of charge density and potentials and the computation of their associated matrix elements. Here, we describe the more recent implementations on top of that core scheme, which include full spin-orbit interaction, non-repeated and multiple-contact ballistic electron transport, density functional theory (DFT)+U and hybrid functionals, time-dependent DFT, novel reduced-scaling solvers, density-functional perturbation theory, efficient van der Waals non-local density functionals, and enhanced molecular-dynamics options. In addition, a substantial effort has been made in enhancing interoperability and interfacing with other codes and utilities, such as wannier90 and the second-principles modeling it can be used for, an AiiDA plugin for workflow automatization, interface to Lua for steering Siesta runs, and various post-processing utilities. Siesta has also been engaged in the Electronic Structure Library effort from its inception, which has allowed the sharing of various low-level libraries, as well as data standards and support for them, particularly the PSeudopotential Markup Language definition and library for transferable pseudopotentials, and the interface to the ELectronic Structure Infrastructure library of solvers. Code sharing is made easier by the new open-source licensing model of the program. This review also presents examples of application of the capabilities of the code, as well as a view of on-going and future developments.

A Mechanically Tunable Quantum Dot in a Graphene Break Junction.

Graphene quantum dots (QDs) are intensively studied as platforms for the next generation of quantum electronic devices. Fine tuning of the transport properties in monolayer graphene QDs, in particular with respect to the independent modulation of the tunnel barrier transparencies, remains challenging and is typically addressed using electrostatic gating. We investigate charge transport in back-gated graphene mechanical break junctions and reveal Coulomb blockade physics characteristic of a single, high-quality QD when a nanogap is opened in a graphene constriction. By mechanically controlling the distance across the newly formed graphene nanogap, we achieve reversible tunability of the tunnel coupling to the drain electrode by 5 orders of magnitude, while keeping the source-QD tunnel coupling constant. The break junction device can therefore become a powerful platform to study the physical parameters that are crucial to the development of future graphene-based devices, including energy converters and quantum calorimeters.

An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis.

The role of T cells in autoimmune encephalitis syndromes with autoantibodies against cell surface antigens is still enigmatic. Here we analyzed the T cell receptor repertoires of CD8+ and CD4+ T cells in a patient with "idiopathic" gamma-aminobutyric-acid-A receptor (GABAA -R) encephalitis by next-generation sequencing and single-cell analyses. We identified a CD8+ T cell clone that was strongly expanded in the cerebrospinal fluid and in the hippocampus but not in the operculo-insular cortex. By contrast, CD4+ T cells were polyclonal in these tissues. Such a strong clonal expansion suggests that CD8+ T cells may play a significant role in the pathogenesis.

In-situ formation of one-dimensional coordination polymers in molecular junctions.

We demonstrate the bottom-up in-situ formation of organometallic oligomer chains at the single-molecule level. The chains are formed using the mechanically controllable break junction technique operated in a liquid environment, and consist of alternating isocyano-terminated benzene monomers coordinated to gold atoms. We show that the chaining process is critically determined by the surface density of molecules. In particular, we demonstrate that by reducing the local supply of molecules within the junction, either by lowering the molecular concentration or by adding side groups, the oligomerization process can be suppressed. Our experimental results are supported by ab-initio simulations, confirming that the isocyano terminating groups display a high tendency to form molecular chains, as a result of their high affinity for gold. Our findings open the road for the controlled formation of one-dimensional, single coordination-polymer chains as promising model systems of organometallic frameworks.

Mechanically controlled quantum interference in graphene break junctions.

The ability to detect and distinguish quantum interference signatures is important for both fundamental research and for the realization of devices such as electron resonators1, interferometers2 and interference-based spin filters3. Consistent with the principles of subwavelength optics, the wave nature of electrons can give rise to various types of interference effects4, such as Fabry-Pérot resonances5, Fano resonances6 and the Aharonov-Bohm effect7. Quantum interference conductance oscillations8 have, indeed, been predicted for multiwall carbon nanotube shuttles and telescopes, and arise from atomic-scale displacements between the inner and outer tubes9,10. Previous theoretical work on graphene bilayers indicates that these systems may display similar interference features as a function of the relative position of the two sheets11,12. Experimental verification is, however, still lacking. Graphene nanoconstrictions represent an ideal model system to study quantum transport phenomena13-15 due to the electronic coherence16 and the transverse confinement of the carriers17. Here, we demonstrate the fabrication of bowtie-shaped nanoconstrictions with mechanically controlled break junctions made from a single layer of graphene. Their electrical conductance displays pronounced oscillations at room temperature, with amplitudes that modulate over an order of magnitude as a function of subnanometre displacements. Surprisingly, the oscillations exhibit a period larger than the graphene lattice constant. Charge-transport calculations show that the periodicity originates from a combination of the quantum interference and lattice commensuration effects of two graphene layers that slide across each other. Our results provide direct experimental observation of a Fabry-Pérot-like interference of electron waves that are partially reflected and/or transmitted at the edges of the graphene bilayer overlap region.

Spin signatures in the electrical response of graphene nanogaps.

We analyse the electrical response of narrow graphene nanogaps in search for transport signatures stemming from spin-polarized edge states. We find that the electrical transport across graphene nanogaps having perfectly defined zigzag edges does not carry any spin-related signature. We also analyse the magnetic and electrical properties of nanogaps whose electrodes have wedges that possibly occur in the currently fabricated nanogaps. These wedges can host spin polarized wedge low-energy states due to the bipartite nature of the graphene lattice. We find that these spin-polarized low-energy modes give rise to low-voltage signatures in the differential conductance and to distinctive features in the stability diagrams. These are caused by fully spin-polarized currents.

Spin-state dependent conductance switching in single molecule-graphene junctions.

Spin-crossover (SCO) molecules are versatile magnetic switches with applications in molecular electronics and spintronics. Downscaling devices to the single-molecule level remains, however, a challenging task since the switching mechanism in bulk is mediated by cooperative intermolecular interactions. Here, we report on electron transport through individual Fe-SCO molecules coupled to few-layer graphene electrodes via π-π stacking. We observe a distinct bistability in the conductance of the molecule and a careful comparison with density functional theory (DFT) calculations allows to associate the bistability with a SCO-induced orbital reconfiguration of the molecule. We find long spin-state lifetimes that are caused by the specific coordination of the magnetic core and the absence of intermolecular interactions according to our calculations. In contrast with bulk samples, the SCO transition is not triggered by temperature but induced by small perturbations in the molecule at any temperature. We propose plausible mechanisms that could trigger the SCO at the single-molecule level.

CISNE: An accurate description of dose-effect and synergism in combination therapies.

The precise determination of dose-effect curves and the combination effect of drugs is of crucial importance in the development of new therapies for the most dreadful diseases. We have found that the current implementations of the theory of Chou et al. are not accurate enough in some circumstances and might lead to erroneous predictions of synergistic or antagonistic behaviour. We have identified the source of inaccuracies and fixed it thereby improving the accuracy of those methods. Here we explain the main features of our approach and demonstrate its higher accuracy as compared to the standard methods. Therefore, this new implementation might have a huge impact in the reliability of future research on new Combination Therapies.

Thermoelectricity in vertical graphene-C60-graphene architectures.

Recent studies of single-molecule thermoelectricity have identified families of high-performance molecules. However, in order to translate this discovery into practical thin-film energy-harvesting devices, there is a need for an understanding of the fundamental issues arising when such junctions are placed in parallel. This is relevant because controlled scalability might be used to boost electrical and thermoelectric performance over the current single-junction paradigm. As a first step in this direction, we investigate here the properties of two C60 molecules placed in parallel and sandwiched between top and bottom graphene electrodes. In contrast with classical conductors, we find that increasing the number of parallel junctions from one to two can cause the electrical conductance to increase by more than a factor of 2. Furthermore, we show that the Seebeck coefficient is sensitive to the number of parallel molecules sandwiched between the electrodes, whereas classically it should be unchanged. This non-classical behaviour of the electrical conductance and Seebeck coefficient are due to inter-junction quantum interference, mediated by the electrodes, which leads to an enhanced response in these vertical molecular devices.

Highly thermally stable and robust enantiopure zirconium NNN-scorpionates for the controlled ring-opening polymerization of rac-lactide.

A series of enantiopure alkoxide and thioalkoxide zirconium derivatives [Zr(ER)3(κ3-R,R-fbpza)] (1-6) (E = O, R = CHMe21, CHMeEt 2, CH2SiMe33, 2,6-C6H3Me24, 4-tBuPh 5; E = S, R = 4-tBuPh 6) has been prepared for use as thermally stable and robust initiators in the ROP of rac-lactide. The compounds were prepared by alcoholysis or thioalcoholysis of the tris(amide) precursor [Zr(NMe2)3(κ3-R,R-fbpza)] [R,R-fbpzaH = N-p-fluorophenyl-(1R)-1-[(1R)-6,6-dimethylbicyclo[3.1.1]-2-hepten-2-yl]-2,2-bis(3,5-dimethylpyrazol-1-yl)ethylamine] with ROH and ArEH (E = O, S) in a 1 : 3 molar ratio. The structures of the different compounds were determined by spectroscopic methods and, in addition, the X-ray crystal structure of 6 was also established. Interestingly, the tris(amide) precursor and complexes 2, 5, and 6 act as single-site living initiators for the well-controlled ring-opening polymerization of rac-lactide both in solution and in the melt. These processes produce polymers with medium molecular weights in good agreement with theoretical values and with narrow dispersity ranges. The activity of all initiators increased markedly with temperature and, more importantly, complex 2 exhibits the highest activity reported to date for a group 4-based initiator in the ROP of rac-LA under the industrially preferred melt and solvent-free conditions. Surprisingly, complex 2 is still highly active in the melt when using an unpurified monomer and it shows an unprecedented tolerance to water and impurities (49% conv., 15 min, 130 °C). Microstructural analysis of the poly(rac-lactide)s revealed a moderate heteroactivity in solution, with a Ps value of up to 0.70.

Structural Phase Transition and Material Properties of Few-Layer Monochalcogenides.

GeSe and SnSe monochalcogenide monolayers and bilayers undergo a two-dimensional phase transition from a rectangular unit cell to a square unit cell at a critical temperature T_{c} well below the melting point. Its consequences on material properties are studied within the framework of Car-Parrinello molecular dynamics and density-functional theory. No in-gap states develop as the structural transition takes place, so that these phase-change materials remain semiconducting below and above T_{c}. As the in-plane lattice transforms from a rectangle into a square at T_{c}, the electronic, spin, optical, and piezoelectric properties dramatically depart from earlier predictions. Indeed, the Y and X points in the Brillouin zone become effectively equivalent at T_{c}, leading to a symmetric electronic structure. The spin polarization at the conduction valley edge vanishes, and the hole conductivity must display an anomalous thermal increase at T_{c}. The linear optical absorption band edge must change its polarization as well, making this structural and electronic evolution verifiable by optical means. Much excitement is drawn by theoretical predictions of giant piezoelectricity and ferroelectricity in these materials, and we estimate a pyroelectric response of about 3×10^{-12} C/K m here. These results uncover the fundamental role of temperature as a control knob for the physical properties of few-layer group-IV monochalcogenides.

Non-canonical NF-κB pathway activation predicts outcome in borderline oestrogen receptor positive breast carcinoma.

BACKGROUND: NF-κB signalling appears deregulated in breast tumours. The purpose of this study was to determine whether the non-canonical NF-κB pathway, is activated in oestrogen receptor positive (ER+) breast cancer, to identify any correlation between its activity and the clinico-pathological phenotype and to explore whether NF-κB2 and RelB subunits and/or any of their target genes might be used as a predictive marker. METHODS: Two independent cohorts of ER+ early breast cancer patients treated with adjuvant endocrine therapy were included in the study. Activation of RelB and NF-κB2 subunits was determined in a training set of 121 patients by measuring DNA-binding activities in nuclear extracts from fresh frozen specimens by an ELISA-based assay. Samples of 15 ER- breast cancer patients were also included in the study. In a large validation cohort of 207 patients, nuclear immunostaining of RelB and NF-κB2 on formalin-fixed paraffin-embedded specimens was performed. Statistical correlation within clinico-pathological factors, disease-free survival (DFS) and overall survival (OS) was evaluated. Publicly available gene expression and survival data have been interrogated aimed to identify target genes. RESULTS: Activation of NF-κB2 and RelB was found in 53.7 and 49.2% of the 121 ER+ tumours analysed, with similar levels to ER- breast tumours analysed in parallel for comparisons. In the validation cohort, we obtained a similar proportion of cases with activation of NF-κB2 and RelB (59.9 and 32.4%), with a 39.6% of co-activation. Multiplexing immunofluorescence in breast cancer tissue confirmed an inverse spatial distribution of ER with NF-κB2 and RelB nuclear expression in tumour cells. Interestingly, NF-κB2 and RelB mRNA expression was inversely correlated with ER gene (ESR1) levels (P<0.001, both) and its activation was significantly associated with worse DFS (P=0.005 and P=0.035, respectively) in ER+ breast cancer. Moreover, the co-activation of both subunits showed a stronger association with early relapse (P=0.002) and OS (P=0.001). Finally, higher expression of the non-canonical NF-κB target gene myoglobin was associated with a poor outcome in ER+ breast cancer (DFS, P<0.05). CONCLUSIONS: The non-canonical NF-κB pathway activation is inversely associated with oestrogen receptor expression in ER+ breast cancer and predicts poor survival in this subgroup. The myoglobin gene expression has been identified as a possible surrogate marker of the non-canonical NF-κB pathway activation in these tumours.

Synthesis and Single-Molecule Conductance Study of Redox-Active Ruthenium Complexes with Pyridyl and Dihydrobenzo[b]thiophene Anchoring Groups.

The ancillary ligands 4'-(4-pyridyl)-2,2':6',2''-terpyridine and 4'-(2,3-dihydrobenzo[b]thiophene)-2,2'-6',2"-terpyridine were used to synthesize two series of mono- and dinuclear ruthenium complexes differing in their lengths and anchoring groups. The electrochemical and single-molecular conductance properties of these two series of ruthenium complexes were studied experimentally by means of cyclic voltammetry and the scanning tunneling microscopy-break junction technique (STM-BJ) and theoretically by means of density functional theory (DFT). Cyclic voltammetry data showed clear redox peaks corresponding to both the metal- and ligand-related redox reactions. Single-molecular conductance demonstrated an exponential decay of the molecular conductance with the increase in molecular length for both the series of ruthenium complexes, with decay constants of ßPY =2.07±0.1 nm(-1) and ßBT =2.16±0.1 nm(-1) , respectively. The contact resistance of complexes with 2,3-dihydrobenzo[b]thiophene (BT) anchoring groups is found to be smaller than the contact resistance of ruthenium complexes with pyridine (PY) anchors. DFT calculations support the experimental results and provided additional information on the electronic structure and charge transport properties in those metal|ruthenium complex|metal junctions.

SN1 reactions in supercritical carbon dioxide in the presence of alcohols: the role of preferential solvation.

Ethanol () inhibits SN1 reactions of alkyl halides in supercritical carbon dioxide (scCO2) and gives no ethers as products. The unexpected behaviour of alcohols in the reaction of alkyl halides with 1,3-dimethoxybenzene () in scCO2 under different conditions is rationalised in terms of Brønsted and Lewis acid-base equilibria of reagents, intermediates, additives and products in a singular solvent characterised by: (i) the strong quadrupole and Lewis acid character of carbon dioxide, which hinders SN2 paths by strongly solvating basic solutes; (ii) the weak Lewis base character of carbon dioxide, which prevents it from behaving as a proton sink; (iii) the compressible nature of scCO2, which enhances the impact of preferential solvation on carbon dioxide availability for the solvent-demanding rate determining step.

Tris(pentafluorophenyl)borane as an efficient catalyst in the guanylation reaction of amines.

Tris(pentafluorophenyl)borane, [B(C6F5)3], has been used as an efficient catalyst in the guanylation reaction of amines with carbodiimide under mild conditions. A combined approach involving NMR spectroscopy and DFT calculations was employed to gain a better insight into the mechanistic features of this process. The results allowed us to propose a new Lewis acid-assisted Brønsted acidic pathway for the guanylation reaction. The process starts with the interaction of tris(pentafluorphenyl)borane and the amine to form the corresponding adduct, [(C6F5)3B-NRH2] , followed by a straightforward proton transfer to one of the nitrogen atoms of the carbodiimide, (i)PrN[double bond, length as m-dash]C[double bond, length as m-dash]N(i)Pr, to produce, in two consequent steps, a guanidine-borane adduct, [(C6F5)3B-NRC(N(i)PrH)2] . The rupture of this adduct liberates the guanidine product RNC(N(i)PrH)2 and interaction with additional amine restarts the catalytic cycle. DFT studies have been carried out in order to study the thermodynamic characteristics of the proposed pathway. Significant borane adducts with amines and guanidines have been isolated and characterized by multinuclear NMR in order to study the N-B interaction and to propose the existence of possible Frustrated Lewis Pairs. Additionally, the molecular structures of significant components of the catalytic cycle, namely 4-tert-butylaniline-[B(C6F5)3] adduct and both free and [B(C6F5)3]-bonded 1-(phenyl)-2,3-diisopropylguanidine, and respectively, have been established by X-ray diffraction.

Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases.

BACKGROUND & AIMS: Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI. METHODS: Twenty-two males (70 ± 8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150 ± 50 mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed. RESULTS: From 1993 to 2013, 22 patients were retrieved. Latency was 163 ± 97 days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18 ± 13 × ULN, ALP 0.7 ± 0.7 × ULN and total serum bilirubin 14 ± 10 mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%). CONCLUSIONS: CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient.

Systematic pseudopotentials from reference eigenvalue sets for DFT calculations: Pseudopotential files.

We present in this article a pseudopotential (PP) database for DFT calculations in the context of the SIESTA code [1-3]. Comprehensive optimized PPs in two formats (psf files and input files for ATM program) are provided for 20 chemical elements for LDA and GGA exchange-correlation potentials. Our data represents a validated database of PPs for SIESTA DFT calculations. Extensive transferability tests guarantee the usefulness of these PPs.