Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus.

BACKGROUND: Antibody-binding of blood dendritic cell antigen 2 (BDCA2), which is expressed exclusively on plasmacytoid dendritic cells, suppresses the production of type I interferon that is involved in the pathogenesis of systemic lupus erythematosus (SLE). The safety and efficacy of subcutaneous litifilimab, a humanized monoclonal antibody that binds to BDCA2, in patients with SLE have not been extensively studied. METHODS: We conducted a phase 2 trial of litifilimab involving participants with SLE. The initial trial design called for randomly assigning participants to receive litifilimab (at a dose of 50, 150, or 450 mg) or placebo administered subcutaneously at weeks 0, 2, 4, 8, 12, 16, and 20, with the primary end point of evaluating cutaneous lupus activity. The trial design was subsequently modified; adults with SLE, arthritis, and active skin disease were randomly assigned to receive either litifilimab at a dose of 450 mg or placebo. The revised primary end point was the change from baseline in the total number of active joints (defined as the sum of the swollen joints and the tender joints) at week 24. Secondary end points were changes in cutaneous and global disease activity. Safety was also assessed. RESULTS: A total of 334 adults were assessed for eligibility, and 132 underwent randomization (64 were assigned to receive 450-mg litifilimab, 6 to receive 150-mg litifilimab, 6 to receive 50-mg litifilimab, and 56 to receive placebo). The primary analysis was conducted in the 102 participants who had received 450-mg litifilimab or placebo and had at least four tender and at least four swollen joints. The mean (±SD) baseline number of active joints was 19.0±8.4 in the litifilimab group and 21.6±8.5 in the placebo group. The least-squares mean (±SE) change from baseline to week 24 in the total number of active joints was -15.0±1.2 with litifilimab and -11.6±1.3 with placebo (mean difference, -3.4; 95% confidence interval, -6.7 to -0.2; P = 0.04). Most of the secondary end points did not support the results of the analysis of the primary end point. Receipt of litifilimab was associated with adverse events, including two cases of herpes zoster and one case of herpes keratitis. CONCLUSIONS: In a phase 2 trial involving participants with SLE, litifilimab was associated with a greater reduction from baseline in the number of swollen and tender joints than placebo over a period of 24 weeks. Longer and larger trials are required to determine the safety and efficacy of litifilimab for the treatment of SLE. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).

Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus.

BACKGROUND: Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied. METHODS: In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. We used a dose-response model to assess whether there was a response across the four groups on the basis of the primary end point, which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more widespread or severe skin involvement). Safety was also assessed. RESULTS: A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. Mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in CLASI-A score at week 16 was -24.3 percentage points (95% confidence interval [CI] -43.7 to -4.9) in the 50-mg litifilimab group, -33.4 percentage points (95% CI, -52.7 to -14.1) in the 150-mg group, and -28.0 percentage points (95% CI, -44.6 to -11.4) in the 450-mg group. The least squares mean changes were used in the primary analysis of a best-fitting dose-response model across the three drug-dose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab. CONCLUSIONS: In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).

Assessment of In Vitro Tests as Predictors of the Antioxidant Effects of Insulin, Metformin, and Taurine in the Brain of Diabetic Rats.

Hyperglycemia-induced oxidative stress is an intrinsic feature of diabetes mellitus and a recognized causative factor of complications associated with the disease. As a result, compounds possessing antioxidant properties are commonly investigated as possible ways of minimizing and even preventing diabetes-related oxidative stress. On these premises, the present study was carried out to investigate the antioxidant properties of metformin (MET), a common oral hypoglycemic agent, of taurine (TAU), a sulfonic acid compound with known antioxidant benefits in diabetes, and of insulin (INS), a standard antidiabetic serving as a reference compound, by using in vitro and in vivo tests. A battery of seven in vitro tests was used to assess antioxidant/antiradical activity. The addition of a treatment compound led to a mean percentage decrease of values for free radical/lipid peroxidation (LPO) that ranged from very high (82%) with INS to moderate (43%) with MET) and to low (31%) with TAU. Combining MET with TAU leads to an improvement of the effect seen with MET alone (46%). By contrast, under the same conditions, N-acetylcysteine, a known antioxidant, was more potent (92%) than any of the test compounds. In vivo studies were conducted using rats made diabetic with streptozotocin and treated with daily doses of INS, MET, TAU, and MET-TAU for 6 weeks. Among the test compounds, the greatest hypoglycemic effect was attained with INS (>90% decrease), followed by MET (~70% decrease), with TAU providing only a modest effect (-30% decrease). Unexpectedly, however, all three compounds reduced the diabetic values for brain LPO, nitric oxide, antioxidant enzymes, glutathione, and glutathione-related enzymes to values that varied in extent within a narrow range (<12% from one another). On the other hand, pairing MET with TAU led to a small enhancement (<10%) of the effects seen with MET alone. In short, while in vitro tests for antioxidant/antiradical activity suggest marked differences in potency for INS, MET, and TAU as a result of different structures, changes in the values of indices of oxidative stress affected by these compounds in the brain of diabetic rats varied within a rather narrow range. Also, the present results suggest that although hyperglycemia is an important determinant of the oxidative stress of diabetes, other factors may be involved since a weak hypoglycemic like TAU demonstrated in vivo antioxidant actions that were comparable to those of more potent hypoglycemic agents like INS and MET.

Investigation of the Role of a Supplementation with Taurine on the Effects of Hypoglycemic-Hypotensive Therapy Against Diabetes-Induced Nephrotoxicity in Rats.

This study has examined the role of supplementing a treatment of diabetic rats with captopril (CAP), metformin (MET) or CAP-MET with the antioxidant amino acid taurine (TAU) on biochemical indices of diabetes-induced metabolic changes, oxidative stress and nephropathy. To this end, groups of 6 male Sprague-Dawley rats (250-375 g) were made diabetic with a single, 60 mg/kg, intraperitoneal dose of streptozotocin (STZ) in 10 mM citrate buffer pH 4.5 and, after 14 days, treated daily for up to 42 days with either a single oral dose of CAP (0.15 mM/kg), MET (2.4 mM/kg) or TAU (2.4 mM/kg), or with a binary or tertiary combination of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. All rats were sacrificed by decapitation on day 57 and their blood and kidneys collected. In addition, a 24 h urine sample was collected starting on day 56. Compared to normal rats, untreated diabetic ones exhibited frank hyperglycemia (+313%), hypoinsulinemia (-76%) and elevation of the glycated hemoglobin value (HbA1c, +207%). Also they showed increased plasma levels of Na+ (+35%), K+ (+56%), creatinine (+232%), urea nitrogen (+158%), total protein (-53%) and transforming growth factor-ß1 (TGF-ß1, 12.4-fold) values. These changes were accompanied by increases in the renal levels of malondialdehyde (MDA, +42%), by decreases in the renal glutathione redox state (-71%), and activities of catalase (-70%), glutathione peroxidase (-71%) and superoxide dismutase (-85%), and by moderate decreases of the urine Na+ (-33%) and K+ (-39%) values. Following monotherapy, MET generally showed a greater attenuating effect than CAP or TAU on the changes in circulating glucose, insulin and HbA1c levels, urine total protein, and renal SOD activity; and CAP appeared more potent than TAU and MET, in that order, in antagonizing the changes in plasma creatinine and urea nitrogen levels. On the other hand, TAU generally provided a greater protection against changes in glutathione redox state and in CAT and GPx activities, with other actions falling in potency between those of CAP and MET. Adding TAU to a treatment with CAP, but not to one with MET, led to an increase in protective action relative to a treatment with drug alone. On the other hand, the actions of CAP-MET, which were about equipotent with those of MET, became enhanced in the presence of TAU, particularly against the changes of the glutathione redox state and activities of antioxidant enzymes. In short, the present results suggest that the addition of TAU to a treatment of diabetes with CAP or CAP-MET, and sometimes to one with MET, will lead to a gain in protective potency against changes in indices of glucose metabolism and of renal functional impairment and oxidative stress.

The Effect of Metformin and Taurine, Alone and in Combination, on the Oxidative Stress Caused by Diabetes in the Rat Brain.

This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combination, on the oxidative stress caused by diabetes in the rat brain. For this purpose, male Sprague-Dawley rats, 200-225 g in weight, assigned to groups of 6, were intraperitoneally (i.p.) treated with the diabetogen streptozotocin (STZ, 60 mg/kg, in citrate buffer pH 4.5) on day 1 and, after 14 days, orally (p.o.) with either MET, TAU or MET-TAU (each at 2.4 mM/kg, in water). Control rats received only citrate buffer pH 4.5 (2 mL) or only STZ on day 1 by the i.p. route. All the animals were sacrificed by decapitation on day 57 and their brains collected by the freeze clamp technique. Blood samples were placed in heparinized tubes and used for the assay of the plasma glucose (GLC) and blood insulin (INS) levels. Immediately thereafter, the brains were surgically removed and a portion was used to prepare a homogenate in 0.1 M PBS pH 7.4, which was used for the assay of indices of oxidative stress. Diabetes raised the plasma GLC level (+313%) but lowered that of the blood INS (-76%) compared to corresponding values from nondiabetic rats. In addition it raised the brain malondialdehyde level (+59%) but lowered the reduced/disulfide glutathione ratio (-46%), and activities of catalase (-43%), glutathione peroxidase (-48%), superoxide dismutase (-65%), glutathione reductase (-50%) and glutathione S-transferase (-51%) significantly (all at p < 0.001). Except for the greater decrease in GLC (+90% vs. +22%) and increase in INS (-26% vs. -52%) levels seen in rats receiving MET than in rats receiving TAU, these compounds protected the brain against oxidative stress to significant (p ≤ 0.05%) and rather similar extents. Furthermore, the concurrent administration of MET and TAU to the diabetic rats led to brain values of indices of oxidative stress that were lower than those attained with MET alone, although generally not to a statistically significant degree.

The high-resolution crystal structure of a parallel intermolecular DNA G-4 quadruplex/drug complex employing syn glycosyl linkages.

We have determined the X-ray structure of the complex between the DNA quadruplex d(5'-GGGG-3')(4) and daunomycin, as a potential model for studying drug-telomere interactions. The structure was solved at 1.08 Å by direct methods in space group I4. The asymmetric unit comprises a linear arrangement of one d(GGGG) strand, four daunomycin molecules, a second d(GGGG) strand facing in the opposite direction to the first, and Na and Mg cations. The crystallographic 4-fold axis generates the biological unit, which is a 12-layered structure comprising two sets of four guanine layers, with four layers each of four daunomycins stacked between the 5' faces of the two quadruplexes. The daunomycin layers fall into two groups which are novel in their mode of self assembly. The only contacts between daunomycin molecules within any one of these layers are van der Waals interactions, however there is substantial π-π stacking between successive daunomycin layers and also with adjacent guanine layers. The structure differs significantly from all other parallel d(TGGGGT)(4) quadruplexes in that the 5' guanine adopts the unusual syn glycosyl linkage, refuting the widespread belief that such conformations should all be anti. In contrast to the related d(TGGGGT)/daunomycin complex, there are no ligand-quadruplex groove insertion interactions.

Cross-bridged cyclen or cyclam Co(III) complexes containing cytotoxic ligands as hypoxia-activated prodrugs.

A series of cobalt(III) complexes of the potent DNA minor groove alkylator (1-(chloromethyl)-5-hydroxy-1H-pyrrolo[3,2-f]quinolin-3(2H)-yl)(5,6,7-trimethoxy-1H-indol-2-yl)methanone (3; seco-CPyI-TMI), with cyclam or cyclen auxiliary ligands (L3 and L5) containing a cross-bridging ethylene (CH2CH2) group or the N,N'-dimethyl derivatives of these (L4 and L6), was prepared. Two 8-quinolinato (2) model complexes of these, [Co(L3)(2)](ClO4)2 and [Co(L6)(2)](ClO4)2, and the aquated derivative [Co(L6)(H2O)2](OTf)3 were characterized by X-ray crystallography. Electrochemistry of the 8-quinolinato model complexes showed that the Co(III)/(II) reduction potential was lowered relative to the unsubstituted cyclen ligand. Evaluation of the cytotoxicity of the racemic seco-CPyI cobalt complexes in vitro showed considerable attenuation of their cytotoxicity relative to the free alkylator and marked hypoxic selectivity, especially [Co(L3)(3)](2+) (9), which was 81-212-fold more potent under hypoxia than 20% oxygen in a panel of 10 human tumor cell lines. However, 9 did not elicit significant killing of hypoxic cells in HT29 tumor xenografts, suggesting possible pharmacological limitations in vivo.

Comparative evaluation of taurine and thiotaurine as protectants against diabetes-induced nephropathy in a rat model.

Taking into account the proven effectiveness of antioxidants in preventing experimentally induced diabetes in laboratory animals, this study was carried out with the specific purpose of comparing the effectiveness of two known antioxidants, the ß-aminosulfonate taurine (TAU) and ß-aminothiosulfonate thiotaurine (TTAU), in preventing biochemical, functional and histological alterations indicative of -diabetic nephropathy. In the study, streptozotocin (60 mg/kg, orally) was used to induce type 2 diabetes mellitus in Sprague-Dawley rats. Starting on day 15 and continuing up to day 56, the rats received a daily single 2.4 mmol/kg oral dose of a sulfur-containing compound (TAU or TTAU) or 4 U/kg subcutaneous dose of isophane insulin (INS). Rats not receiving any treatment served as controls. After obtaining a 24 h urine sample, the animals were sacrificed by decapitation on day 57, and their blood and kidneys immediately collected. Diabetic rats exhibited marked hyperglycemia, hypoinsulinemia, hypoproteinemia, hyponatremia, hyperkalemia, azotemia, hypercreatinemia, increased plasma TGF ß(1), lipid peroxidation, plasma and kidney nitrite, and urine output; decreased glutathione redox status in plasma and kidney, decreased urine Na(+) and K(+), proteinuria and hypocreatinuria. Without exceptions, all the treatment compounds were found to markedly and variously attenuate these changes. Confirmation of protection by INS, TAU and TTAU was provided by the results of histological examination of kidney sections and which showed a more normal appearance than sections from diabetic animals. In most instances protection by TTAU was about equal to that by INS but greater than that by TAU.

Flight demonstration of a miniature atomic scalar magnetometer based on a microfabricated rubidium vapor cell.

We have developed an atomic magnetometer based on the rubidium isotope 87Rb and a microfabricated silicon/glass vapor cell for the purpose of qualifying the instrument for space flight during a ride-along opportunity on a sounding rocket. The instrument consists of two scalar magnetic field sensors mounted at 45° angle to avoid measurement dead zones, and the electronics consist of a low-voltage power supply, an analog interface, and a digital controller. The instrument was launched into the Earth's northern cusp from Andøya, Norway on December 8, 2018 on the low-flying rocket of the dual-rocket Twin Rockets to Investigate Cusp Electrodynamics 2 mission. The magnetometer was operated without interruption during the science phase of the mission, and the acquired data were compared favorably with those from the science magnetometer and the model of the International Geophysical Reference Field to within an approximate fixed offset of about 550 nT. Residuals with respect to these data sources are plausibly attributed to offsets resulting from rocket contamination fields and electronic phase shifts. These offsets can be readily mitigated and/or calibrated for a future flight experiment so that the demonstration of this absolute-measuring magnetometer was entirely successful from the perspective of increasing the technological readiness for space flight.

Plasma Environment, Radiation, Structure, and Evolution of the Uranian System (PERSEUS): A Dedicated Orbiter Mission Concept to Study Space Physics at Uranus.

The Plasma Environment, Radiation, Structure, and Evolution of the Uranian System (PERSEUS) mission concept defines the feasibility and potential scope of a dedicated, standalone Heliophysics orbiter mission to study multiple space physics science objectives at Uranus. Uranus's complex and dynamic magnetosphere presents a unique laboratory to study magnetospheric physics as well as its coupling to the solar wind and the planet's atmosphere, satellites, and rings. From the planet's tilted and offset, rapidly-rotating non-dipolar magnetic field to its seasonally-extreme interactions with the solar wind to its unexpectedly intense electron radiation belts, Uranus hosts a range of outstanding and compelling mysteries relevant to the space physics community. While the exploration of planets other than Earth has largely fallen within the purview of NASA's Planetary Science Division, many targets, like Uranus, also hold immense scientific value and interest to NASA's Heliophysics Division. Exploring and understanding Uranus's magnetosphere is critical to make fundamental gains in magnetospheric physics and the understanding of potential exoplanetary systems and to test the validity of our knowledge of magnetospheric dynamics, moon-magnetosphere interactions, magnetosphere-ionosphere coupling, and solar wind-planetary coupling. The PERSEUS mission concept study, currently at Concept Maturity Level (CML) 4, comprises a feasible payload that provides closure to a range of space physics science objectives in a reliable and mature spacecraft and mission design architecture. The mission is able to close using only a single Mod-1 Next-Generation Radioisotope Thermoelectric Generator (NG-RTG) by leveraging a concept of operations that relies of a significant hibernation mode for a large portion of its 22-day orbit.

Properties of Ion-Inertial Scale Plasmoids Observed by the Juno Spacecraft in the Jovian Magnetotail.

We expand on previous observations of magnetic reconnection in Jupiter's magnetosphere by constructing a survey of ion-inertial scale plasmoids in the Jovian magnetotail. We developed an automated detection algorithm to identify reversals in the B θ component and performed the minimum variance analysis for each identified plasmoid to characterize its helical structure. The magnetic field observations were complemented by data collected using the Juno Waves instrument, which is used to estimate the total electron density, and the JEDI energetic particle detectors. We identified 87 plasmoids with "peak-to-peak" durations between 10 and 300 s. Thirty-one plasmoids possessed a core field and were classified as flux-ropes. The other 56 plasmoids had minimum field strength at their centers and were termed O-lines. Out of the 87 plasmoids, 58 had in situ signatures shorter than 60 s, despite the algorithm's upper limit being 300 s, suggesting that smaller plasmoids with shorter durations were more likely to be detected by Juno. We estimate the diameter of these plasmoids assuming a circular cross section and a travel speed equal to the Alfven speed in the surrounding lobes. Using the electron density inferred by Waves, we contend that these plasmoid diameters were within an order of the local ion-inertial length. Our results demonstrate that magnetic reconnection in the Jovian magnetotail occurs at ion scales like in other space environments. We show that ion-scale plasmoids would need to be released every 0.1 s or less to match the canonical 1 ton/s rate of plasma production due to Io.

A Preliminary Study of Magnetosphere-Ionosphere-Thermosphere Coupling at Jupiter: Juno Multi-Instrument Measurements and Modeling Tools.

The dynamics of the Jovian magnetosphere are controlled by the interplay of the planet's fast rotation, its main iogenic plasma source and its interaction with the solar wind. Magnetosphere-Ionosphere-Thermosphere (MIT) coupling processes controlling this interplay are significantly different from their Earth and Saturn counterparts. At the ionospheric level, they can be characterized by a set of key parameters: ionospheric conductances, electric currents and fields, exchanges of particles along field lines, Joule heating and particle energy deposition. From these parameters, one can determine (a) how magnetospheric currents close into the ionosphere, and (b) the net deposition/extraction of energy into/out of the upper atmosphere associated to MIT coupling. We present a new method combining Juno multi-instrument data (MAG, JADE, JEDI, UVS, JIRAM and Waves) and modeling tools to estimate these key parameters along Juno's trajectories. We first apply this method to two southern hemisphere main auroral oval crossings to illustrate how the coupling parameters are derived. We then present a preliminary statistical analysis of the morphology and amplitudes of these key parameters for eight among the first nine southern perijoves. We aim to extend our method to more Juno orbits to progressively build a comprehensive view of Jovian MIT coupling at the level of the main auroral oval.

Revealing the source of Jupiter's x-ray auroral flares.

Jupiter's rapidly rotating, strong magnetic field provides a natural laboratory that is key to understanding the dynamics of high-energy plasmas. Spectacular auroral x-ray flares are diagnostic of the most energetic processes governing magnetospheres but seemingly unique to Jupiter. Since their discovery 40 years ago, the processes that produce Jupiter's x-ray flares have remained unknown. Here, we report simultaneous in situ satellite and space-based telescope observations that reveal the processes that produce Jupiter's x-ray flares, showing surprising similarities to terrestrial ion aurora. Planetary-scale electromagnetic waves are observed to modulate electromagnetic ion cyclotron waves, periodically causing heavy ions to precipitate and produce Jupiter's x-ray pulses. Our findings show that ion aurorae share common mechanisms across planetary systems, despite temporal, spatial, and energetic scales varying by orders of magnitude.

Functionalization of metallabenzenes through nucleophilic aromatic substitution of hydrogen.

The cationic metallabenzenes [Ir(C(5)H(4){SMe-1})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (1) and [Os(C(5)H(4){SMe-1})(CO)(2)(PPh(3))(2)][CF(3)SO(3)] (2) undergo regioselective nucleophilic aromatic substitution of hydrogen at the metallabenzene ring position γ to the metal in a two-step process that first involves treatment with appropriate nucleophiles and then oxidation. Thus, reaction between compound 1 and NaBH(4), MeLi, or NaOEt gives the corresponding neutral iridacyclohexa-1,4-diene complexes Ir(C(5)H(3){SMe-1}{H-3}{Nu-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2) (Nu = H (3), Me (4), OEt (5)). Similarly, reaction between 2 and NaBH(4) or MeLi gives the corresponding osmacyclohexa-1,4-diene complexes Os(C(5)H(3){SMe-1}{H-3}{Nu-3})(CO)(2)(PPh(3))(2) (Nu = H (8), Me (9)). The metallacyclohexa-1,4-diene rings in all these compounds are rearomatized on treatment with the oxidizing agent O(2), CuCl(2), or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Accordingly, the cationic metallabenzene 1 or 2 is returned after reaction between 3 and DDQ/NEt(4)PF(6) or between 8 and DDQ/NaO(3)SCF(3), respectively. The substituted cationic iridabenzene [Ir(C(5)H(3){SMe-1}{Me-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (6) or [Ir(C(5)H(4){SMe-1}{OEt-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (7) is produced in a similar manner through reaction between 4 or 5, respectively, and DDQ/NEt(4)PF(6), and the substituted cationic osmabenzene [Os(C(5)H(3){SMe-1}{Me-3})(CO)(2)(PPh(3))(2)]Cl (10) is formed in good yield on treatment of 9 with CuCl(2). The starting cationic iridabenzene 1 is conveniently prepared by treatment of the neutral iridabenzene Ir(C(5)H(4){SMe-1})Cl(2)(PPh(3))(2) with NaS(2)CNEt(2) and NEt(4)PF(6), and the related starting cationic osmabenzene 2 is obtained by treatment of Os(C(5)H(4){S-1})(CO)(PPh(3))(2) with CF(3)SO(3)CH(3) and CO. The stepwise transformations of 1 into 6 or 7 as well as 2 into 10 provide the first examples in metallabenzene chemistry of regioselective nucleophilic aromatic substitutions of hydrogen by external nucleophiles. DFT calculations have been used to rationalize the preferred sites for nucleophilic attack at the metallabenzene rings of 1 and 2. The crystal structures of 1, 3, 6, and 7 have been obtained.

Magnetotail Reconnection at Jupiter: A Survey of Juno Magnetic Field Observations.

At Jupiter, tail reconnection is thought to be driven by an internal mass loading and release process called the Vasyliunas cycle. Galileo data have shown hundreds of reconnection events occurring in Jupiter's magnetotail. Here we present a survey of reconnection events observed by Juno during its first 16 orbits of Jupiter (July 2016-October 2018). The events are identified using Juno magnetic field data, which facilitates comparison to the Vogt et al. (2010, https://doi.org/10.1029/2009JA015098) survey of reconnection events from Galileo magnetometer data, but we present data from Juno's other particle and fields instruments for context. We searched for field dipolarizations or reversals and found 232 reconnection events in the Juno data, most of which featured an increase in |B θ |, the magnetic field meridional component, by a factor of 3 over background values. We found that most properties of the Juno reconnection events, like their spatial distribution and duration, are comparable to Galileo, including the presence of a ~3-day quasi-periodicity in the recurrence of Juno tail reconnection events and in Juno JEDI, JADE, and Waves data. However, unlike with Galileo we were unable to clearly define a statistical x-line separating planetward and tailward Juno events. A preliminary analysis of plasma velocities during five magnetic field reconnection events showed that the events were accompanied by fast radial flows, confirming our interpretation of these magnetic signatures as reconnection events. We anticipate that a future survey covering other Juno datasets will provide additional insight into the nature of tail reconnection at Jupiter.

Bis[(1S*,2S*)-trans-1,2-bis-(diphenyl-phosphin-oxy)cyclo-hexa-ne]chlorido-ruthenium(II) trifluoro-methane-sulfonate dichloro-methane disolvate.

The crystal structure of a racemic mixture of the title ruthenium(II) complex, [RuCl(C(30)H(30)O(2)P(2))(2)]CF(3)SO(3)·2CH(2)Cl(2), reveals that the coordination geometry about the coordinatively unsaturated metal centre is approximately trigonal-pyramidal, with the chlorine atom occupying one of the equatorial positions. The axial Ru-P bonds are longer than the equatorial Ru-P bonds and there is an acute P-Ru-P angle.

Synthetic routes to mixed-ligand cobalt(III) dithiocarbamato complexes containing imidazole, amine and pyridine donors and the X-ray crystal structure of a cobalt(III) bis(dithiocarbamato) histamine complex.

The binuclear cobalt complex [Co(2)(Me(2)dtc)(5)](+) reacts with a range of nitrogen donor ligands L' or L'' to form an equimolar mixture of Co(Me(2)dtc)(3) and the mixed-ligand complexes [Co(Me(2)dtc)(2)(L')(2)](+) or [Co(Me(2)dtc)(2)(L'')](+), where (L')(2) is two monodentate ligands and (L'') is one bidentate ligand. The complexes prepared by this route contain the monodentate ligands L'=1-methyl-imidazole, 1-methyl-5-nitro-imidazole and benzimidazole, all of which coordinate to cobalt through an imidazole nitrogen atom. Symmetrical bidentate ligand complexes contain the bisimidazole L''=2,2'-bis(4,5-dimethylimidazole), the diamine L''=1,2-diaminobenzene and the pyridine donors L''=2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine and 1,10-phenanthroline. Two examples of complexes with unsymmetrical bidentate imidazole-amine donors were prepared in which L''=4-(2-aminoethyl)imidazole (histamine) and 2-aminomethylbenzimidazole. All new complexes were fully characterised, and the X-ray crystal structure of the histamine complex [Co(Me(2)dtc)(2)(hist)]ClO(4) is also reported.

N-[3-(tert-Butyl-dimethyl-siloxymeth-yl)-5-nitro-phen-yl]acetamide.

The title compound, C(15)H(24)N(2)O(4)Si, was prepared by the reaction of (3-acetamido-5-nitro-benz-yl)methanol with tert-butyl-dimethyl-silyl chloride and is a key inter-mediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent mol-ecules in the structure, which differ primarily in the rotation about the C-O bond next to the Si atom. Two strong N-H⋯O hydrogen bonds align the mol-ecules into a wide ribbon extending approximately parallel to the b axis.

2,2'-(3,5-Dinitro-benzyl-imino)diethanol.

The title compound, C(11)H(15)N(3)O(6), was prepared by the reaction of (3,5-dinitro-benz-yl)methane-sulfonate with diethanol-amine. The asymmetric unit contains four crystallographically independent mol-ecules which differ primarily in their rotation about the bond between the aromatic ring and the N-diethanol unit. The mol-ecules are linked into sheets by a hydrogen-bonding network which involves all of the hydroxy groups, with only van der Waals contacts between the sheets.