New Cross-Bridged Cyclam Ligands and Their Transition Metal Complexes as CXCR4 Antagonists

CXCR4 is a co-receptor on the surface of immune cells that has been proven to facilitate the entry of HIV into the cells. Within the last 15 years the CXCR4 and CCR5 coreceptors have influenced new therapeutic approaches to the treatment of HIV via fusion inhibitor drugs that target these receptors. Our aim is to develop new antagonists for the CXCR4 coreceptor. Specifically, the goal was the synthesis of Propyl Cross-Bridged, linked analogues of the known CXCR4 antagonist AMD-3100

First light of the VLT planet finder SPHERE. I. Detection and characterization of the sub-stellar companion GJ 758 B

GJ758 B is a brown dwarf companion to a nearby (15.76 pc) solar-type, metal-rich (M/H = +0.2 dex) main-sequence star (G9V) that was discovered with Subaru/HiCIAO in 2009. From previous studies, it has drawn attention as being the coldest (~600K) companion ever directly imaged around a neighboring star. We present new high-contrast data obtained during the commissioning of the SPHERE instrument at the VLT. The data was obtained in Y-, J-, H-, and Ks-bands with the dual-band imaging (DBI) mode of IRDIS, providing a broad coverage of the full near-infrared (near-IR) range at higher contrast and better spectral sampling than previously reported. In this new set of high-quality data, we report the re-detection of the companion, as well as the first detection of a new candidate closer-in to the star. We use the new 8 photometric points for an extended comparison of GJ758 B with empirical objects and 4 families of atmospheric models. From comparison to empirical object, we estimate a T8 spectral type, but none of the comparison object can accurately represent the observed near-IR fluxes of GJ758 B. From comparison to atmospheric models, we attribute a Teff = 600K $\pm$ 100K, but we find that no atmospheric model can adequately fit all the fluxes of GJ758 B. The photometry of the new candidate companion is broadly consistent with L-type objects, but a second epoch with improved photometry is necessary to clarify its status. The new astrometry of GJ758 B shows a significant proper motion since the last epoch. We use this result to improve the determination of the orbital characteristics using two fitting approaches, Least-Square Monte Carlo and Markov Chain Monte Carlo. Finally, we analyze the sensitivity of our data to additional closer-in companions and reject the possibility of other massive brown dwarf companions down to 4-5 AU. [abridged]Comment: 20 pages, 15 figures. Accepted for publication in A&

First light of the VLT planet finder SPHERE. II. The physical properties and the architecture of the young systems PZ Tel and HD 1160 revisited

[Abridged] Context. The young systems PZ Tel and HD 1160, hosting known low-mass companions, were observed during the commissioning of the new planet finder SPHERE with several imaging and spectroscopic modes. Aims. We aim to refine the physical properties and architecture of both systems. Methods. We use SPHERE commissioning data and REM observations, as well as literature and unpublished data from VLT/SINFONI, VLT/NaCo, Gemini/NICI, and Keck/NIRC2. Results. We derive new photometry and confirm the nearly daily photometric variability of PZ Tel A. Using literature data spanning 38 yr, we show that the star also exhibits a long-term variability trend. The 0.63-3.8 mic SED of PZ Tel B allows us to revise its properties: spectral type M7+/-1, Teff=2700+/-100 K, log(g)<4.5 dex, log(L/L_Sun)=-2.51+/-0.10 dex, and mass 38-72 MJ. The 1-3.8 mic SED of HD 1160 B suggests a massive brown dwarf or a low-mass star with spectral type M5.5-7.0, Teff=3000+/-100 K, [M/H]=-0.5-0.0 dex, log(L/L_Sun)=-2.81+/-0.10 dex, and mass 39-168 MJ. We confirm the deceleration and high eccentricity (e>0.66) of PZ Tel B. For e<0.9, the inclination, longitude of the ascending node, and time of periastron passage are well constrained. The system is seen close to an edge-on geometry. We reject other brown dwarf candidates outside 0.25" for both systems, and massive giant planets (>4 MJ) outside 0.5" for the PZ Tel system. We also show that K1-K2 color can be used with YJH low-resolution spectra to identify young L-type companions, provided high photometric accuracy (<0.05 mag) is achieved. Conclusions. SPHERE opens new horizons in the study of young brown dwarfs and giant exoplanets thanks to high-contrast imaging capabilities at optical and near-infrared wavelengths, as well as high signal-to-noise spectroscopy in the near-infrared from low (R~30-50) to medium resolutions (R~350).Comment: 25 pages, 23 figures, accepted for publication in A&A on Oct. 13th, 2015; version including language editing. Typo on co-author name on astroph page corrected, manuscript unchange

Post conjunction detection of β\beta Pictoris b with VLT/SPHERE

With an orbital distance comparable to that of Saturn in the solar system, \bpic b is the closest (semi-major axis $\simeq$\,9\,au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to \bpic have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters. We aimed at further constraining \bpic b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. We used SPHERE at the VLT to precisely monitor the orbital motion of beta \bpic b since first light of the instrument in 2014. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6\,au) and prevented further detection. We redetected \bpic b on the northeast side of the disk at a separation of 139\,mas and a PA of 30$^{\circ}$ in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of $a = 9.0 \pm 0.5$ au (1 $\sigma$), it definitely excludes previously reported possible long orbital periods, and excludes \bpic b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.Comment: accepted by A&

SPHERE: the exoplanet imager for the Very Large Telescope

Observations of circumstellar environments to look for the direct signal of exoplanets and the scattered light from disks has significant instrumental implications. In the past 15 years, major developments in adaptive optics, coronagraphy, optical manufacturing, wavefront sensing and data processing, together with a consistent global system analysis have enabled a new generation of high-contrast imagers and spectrographs on large ground-based telescopes with much better performance. One of the most productive is the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE) designed and built for the ESO Very Large Telescope (VLT) in Chile. SPHERE includes an extreme adaptive optics system, a highly stable common path interface, several types of coronagraphs and three science instruments. Two of them, the Integral Field Spectrograph (IFS) and the Infra-Red Dual-band Imager and Spectrograph (IRDIS), are designed to efficiently cover the near-infrared (NIR) range in a single observation for efficient young planet search. The third one, ZIMPOL, is designed for visible (VIR) polarimetric observation to look for the reflected light of exoplanets and the light scattered by debris disks. This suite of three science instruments enables to study circumstellar environments at unprecedented angular resolution both in the visible and the near-infrared. In this work, we present the complete instrument and its on-sky performance after 4 years of operations at the VLT.Comment: Final version accepted for publication in A&

Australian Veterinary History Record No. 26

Australian Veterinary Associatio

Crystal structure of dichlorido(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane)iron(III) hexafluoridophosphate

The title compound, [FeCl₂(C₁₄H₃₀N₄)]PF₆, contains Fe³⁺ coordinated by the four nitro­gen atoms of an ethyl­ene cross-bridged cyclam macrocycle and two cis chloride ligands in a distorted octa­hedral environment. In contrast to other similar compounds this is a monomer. Inter­molecular C-H...Cl inter­actions exist in the structure between the complex ions. Comparison with the mononuclear Fe²⁺ complex of the same ligand shows that the smaller Fe³⁺ ion is more fully engulfed by the cavity of the bicyclic ligand. Comparison with the μ-oxido dinuclear complex of an unsubstituted ligand of the same size demonstrates that the methyl groups of 4,11-dimethyl-1,4,8,11-tetra­aza­bicyclo­[6.6.2]hexa­decane prevent dimerization upon oxidation

Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads

© 2019 A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monocyclic polyamines and their transition metal complexes were prepared, chemically characterized, and screened in vitro against the Leishmania donovani promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC 50 and/or IC 90 values showed that 10 compounds were similarly active at about 2-fold less potent than known drug pentamidine against promastigotes. The most potent compound had an IC 50 of 2.82 µM (compared to 2.93 µM for pentamidine). Nine compounds were 1.1–13.6-fold more potent than pentamidine against axenic amastigotes, the most potent one being about 2-fold less potent than amphotericin B. Fourteen compounds were about 2–10 fold more potent than pentamidine, the most potent one is about 2-fold less potent than amphotericin B against intracellular amastigotes in THP1 cells. The 2 most promising compounds (FeL7Cl 2 and MnL7Cl 2 ), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe 2+ - and Mn 2+ -complexes of a dibenzyl cyclen derivative. Only 2 of the 44 compounds showed observable cytotoxicity against THP1 cells. Tetraazamacrocyclic monocyclic polyamines represent a new class of antileishmanial lead structures that warrant follow up studies

Increase of Direct C-C Coupling Reaction Yield by Identifying Structural and Electronic Properties of High-Spin Iron Tetra-azamacrocyclic Complexes

Macrocyclic ligands have been explored extensively as scaffolds for transition metal catalysts for oxygen and hydrogen atom transfer reactions. C–C reactions facilitated using earth abundant metals bound to macrocyclic ligands have not been well-understood but could be a green alternative to replacing the current expensive and toxic precious metal systems most commonly used for these processes. Therefore, the yields from direct Suzuki–Miyaura C–C coupling of phenylboronic acid and pyrrole to produce 2-phenylpyrrole facilitated by eight high-spin iron complexes ([Fe3+L1(Cl)2]+, [Fe3+L4(Cl)2]+, [Fe2+L5(Cl)]+, [Fe2+L6(Cl)2], [Fe3+L7(Cl)2]+, [Fe3+L8(Cl)2]+, [Fe2+L9(Cl)]+, and [Fe2+L10(Cl)]+) were compared to identify the effect of structural and electronic properties on catalytic efficiency. Specifically, catalyst complexes were compared to evaluate the effect of five properties on catalyst reaction yields: (1) the coordination requirements of the catalyst, (2) redox half-potential of each complex, (3) topological constraint/rigidity, (4) N atom modification(s) increasing oxidative stability of the complex, and (5) geometric parameters. The need for two labile cis-coordination sites was confirmed based on a 42% decrease in catalytic reaction yield observed when complexes containing pentadentate ligands were used in place of complexes with tetradentate ligands. A strong correlation between iron(III/II) redox potential and catalytic reaction yields was also observed, with [Fe2+L6(Cl)2] providing the highest yield (81%, −405 mV). A Lorentzian fitting of redox potential versus yields predicts that these catalysts can undergo more fine-tuning to further increase yields. Interestingly, the remaining properties explored did not show a direct, strong relationship to catalytic reaction yields. Altogether, these results show that modifications to the ligand scaffold using fundamental concepts of inorganic coordination chemistry can be used to control the catalytic activity of macrocyclic iron complexes by controlling redox chemistry of the iron center. Furthermore, the data provide direction for the design of improved catalysts for this reaction and strategies to understand the impact of a ligand scaffold on catalytic activity of other reactions