Metal-ligand pair anisotropy in a series of mononuclear Er-COT complexes.

Synthetic control of the crystal field has elevated lanthanides to the forefront of single-molecule magnet (SMM) research, yet the resultant strong, predictable single-ion anisotropy has thus far not translated into equally impressive molecule-based magnets of higher dimensionality. This roadblock arises from the dual demands made of the crystal field: generate anisotropy and facilitate magnetic coupling. Here we demonstrate that particular metal-ligand pairs can dominate the single-ion electronic structure so fully that the remaining coordination sphere plays a minimal role in the magnitude and orientation of the magnetic anisotropy. This Metal-Ligand Pair Anisotropy (MLPA) effectively separates the crystal field into discrete components dedicated to anisotropy and magnetic coupling. To demonstrate an MLPA building unit, we synthesized four new mononuclear complexes that challenge the electronic structure of the iconic lanthanocene ([Ln(COT)2]+; COT2- = cyclooctatetraene dianion) complex which is known to generate strong anisotropy with Ln = Er3+. Variation in symmetry and coordination strength for Er(COT)I(THF)2 (THF = tetrahydrofuran) (1), Er(COT)I(Py)2 (Py = pyridine) (2), Er(COT)I(MeCN)2 (MeCN = acetonitrile) (3), and Er(COT)(Tp*) (Tp* = tris(3,5-dimethyl-1-pyrazolyl)borate) (4) shows that the Er-COT unit stabilizes anisotropy despite deliberate de-optimization. All four half-sandwich complexes display SMM behavior with effective energy barriers of U eff = 95.6(9), 102.9(3.1), 107.1(1.3), and 133.6(2.2) cm-1 for 1-4 by a multi-relaxation-process fitting. More importantly, the basic state splittings remain intact and the anisotropy axes are within several degrees of normal to the COT2- ring according to complete active space self-consistent field (CASSCF) calculations. Further investigation of the MLPA conceptual framework is warranted as it can provide building units with well-defined magnetic orientation and strength. We envision that the through-barrier processes observed herein, such as quantum tunneling, can be mitigated by formation of larger clusters and molecule-based materials

Status of the Planet Formation Imager (PFI) concept

This is the author accepted manuscript. The final version is available from SPIE via the DOI in this record.The Planet Formation Imager (PFI) project aims to image the period of planet assembly directly, resolving structures as small as a giant planet’s Hill sphere. These images will be required in order to determine the key mechanisms for planet formation at the time when processes of grain growth, protoplanet assembly, magnetic fields, disk/planet dynamical interactions and complex radiative transfer all interact – making some planetary systems habitable and others inhospitable. We will present the overall vision for the PFI concept, focusing on the key technologies and requirements that are needed to achieve the science goals. Based on these key requirements, we will define a cost envelope range for the design and highlight where the largest uncertainties lie at this conceptual stage

Status of the Planet Formation Imager (PFI) concept

The Planet Formation Imager (PFI) project aims to image the period of planet assembly directly, resolving structures as small as a giant planet’s Hill sphere. These images will be required in order to determine the key mechanisms for planet formation at the time when processes of grain growth, protoplanet assembly, magnetic fields, disk/planet dynamical interactions and complex radiative transfer all interact – making some planetary systems habitable and others inhospitable. We will present the overall vision for the PFI concept, focusing on the key technologies and requirements that are needed to achieve the science goals. Based on these key requirements, we will define a cost envelope range for the design and highlight where the largest uncertainties lie at this conceptual stage.This is the author accepted manuscript. The final version is available from SPIE via http://dx.doi.org/10.1117/12.223392

Influencing the properties of dysprosium single-molecule magnets with phosphine, phosphide and phosphinidene ligands

Single-molecule magnets are a type of coordination compound that can retain magnetic information at low temperatures. Single-molecule magnets based on lanthanides have accounted for many important advances, including systems with very large energy barriers to reversal of the magnetization, and a di-terbium complex that displays magnetic hysteresis up to 14 K and shows strong coercivity. Ligand design is crucial for the development of new single-molecule magnets: organometallic chemistry presents possibilities for using unconventional ligands, particularly those with soft donor groups. Here we report dysprosium single-molecule magnets with neutral and anionic phosphorus donor ligands, and show that their properties change dramatically when varying the ligand from phosphine to phosphide to phosphinidene. A phosphide-ligated, trimetallic dysprosium single-molecule magnet relaxes via the second-excited Kramers’ doublet, and, when doped into a diamagnetic matrix at the single-ion level, produces a large energy barrier of 256 cm1 and magnetic hysteresis up to 4.4 K

A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors

<p><b>Purpose:</b> This Phase I study assessed whether food influences the rate and extent of selumetinib absorption in patients with advanced solid malignancies and determined the safety, tolerability, and pharmacokinetic (PK) profile of selumetinib and its active metabolite N-desmethyl-selumetinib in fed and fasted states.</p> <p><b>Methods:</b> A single dose of 75 mg selumetinib was to be taken with food on Day 1 followed by a single dose of 75 mg after fasting for at least 10 h on Day 8, or vice versa, followed by twice daily dosing of 75 mg selumetinib from Day 10. Plasma concentrations and PK parameters were determined on Days 1 and 8. Patients could continue to receive selumetinib for as long as they benefitted from treatment.</p> <p><b>Results:</b> In total, 31 patients were randomized to receive selumetinib; 15 to fed/fasted sequence and 16 to fasted/fed sequence. Comprehensive PK sampling was performed on 11 and 10 patients, respectively. The geometric least-squares means of C<sub>max</sub> and AUC for selumetinib were reduced by 62% (ratio 0.38 90% CI 0.29, 0.50) and 19% (ratio 0.81 90% CI 0.74, 0.88), respectively, under fed compared with fasting conditions. The rate of absorption (t<sub>max</sub>) of selumetinib (fed) was delayed by approximately 2.5 h (median). The food effect was also observed for the active metabolite N-desmethyl-selumetinib. Selumetinib was well tolerated.</p> <p><b>Conclusions:</b> The presence of food decreased the extent of absorption of selumetinib. It is recommended that for further clinical studies, selumetinib be taken on an empty stomach. Selumetinib demonstrated an acceptable safety profile in the advanced cancer population.</p&gt

Organometallic neptunium(III) complexes

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements

Rapid Growth Reduces Cold Resistance: Evidence from Latitudinal Variation in Growth Rate, Cold Resistance and Stress Proteins

Background: Physiological costs of rapid growth may contribute to the observation that organisms typically grow at submaximal rates. Although, it has been hypothesized that faster growing individuals would do worse in dealing with suboptimal temperatures, this type of cost has never been explored empirically. Furthermore, the mechanistic basis of the physiological costs of rapid growth is largely unexplored. Methodology/Principal Finding: Larvae of the damselfly Ischnura elegans from two univoltine northern and two multivoltine southern populations were reared at three temperatures and after emergence given a cold shock. Cold resistance, measured by chill coma recovery times in the adult stage, was lower in the southern populations. The faster larval growth rates in the southern populations contributed to this latitudinal pattern in cold resistance. In accordance with their assumed role in cold resistance, Hsp70 levels were lower in the southern populations, and faster growing larvae had lower Hsp70 levels. Yet, individual variation in Hsp70 levels did not explain variation in cold resistance. Conclusions/Significance: We provide evidence for a novel cost of rapid growth: reduced cold resistance. Our results indicate that the reduced cold resistance in southern populations of animals that change voltinism along the latitudinal gradient may not entirely be explained by thermal selection per se but also by the costs of time constraint-induced higher growth rates. This also illustrates that stressors imposed in the larval stage may carry over and shape fitness in the adul

Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster

Drosophila melanogaster is a chill-susceptible insect. Previous studies on this fly focused on acute direct chilling injury during cold shock and showed that lower lethal temperature (LLT, approximately -5°C) exhibits relatively low plasticity and that acclimations, both rapid cold hardening (RCH) and long-term cold acclimation, shift the LLT by only a few degrees at the maximum.We found that long-term cold acclimation considerably improved cold tolerance in fully grown third-instar larvae of D. melanogaster. A comparison of the larvae acclimated at constant 25°C with those acclimated at constant 15°C followed by constant 6°C for 2 d (15°C→6°C) showed that long-term cold acclimation extended the lethal time for 50% of the population (Lt(50)) during exposure to constant 0°C as much as 630-fold (from 0.137 h to 86.658 h). Such marked physiological plasticity in Lt(50) (in contrast to LLT) suggested that chronic indirect chilling injury at 0°C differs from that caused by cold shock. Long-term cold acclimation modified the metabolomic profiles of the larvae. Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the two most prominent responses. In addition, restructuring of the glycerophospholipid composition of biological membranes was observed. The relative proportion of glycerophosphoethanolamines (especially those with linoleic acid at the sn-2 position) increased at the expense of glycerophosphocholines.Third-instar larvae of D. melanogaster improved their cold tolerance in response to long-term cold acclimation and showed metabolic potential for the accumulation of proline and trehalose and for membrane restructuring