Exploring the potential of gold(iii) cyclometallated compounds as cytotoxic agents: variations on the C^N theme

A series of novel ((CN)-N-boolean AND) cyclometallated Au(III) complexes of general formula [Au(py(b)-H)(LL2)-L-1](n+) (py(b)-H = (CN)-N-boolean AND cyclometallated 2-benzylpyridine, L-1 and L-2 being chlorido, phosphane or glucosethiolato ligands, n = 0 or 1) have been synthesized and fully characterized using different techniques, including NMR, IR and far-IR, mass spectrometry, as well as elemental analysis. The crystal structure of one compound has been solved using X-ray diffraction methods. All compounds were tested in vitro in five human cancer cell lines including the lung, breast, colon and ovarian cancer cells. For comparison purposes, all compounds were also tested in a model of healthy human cells from the embryonic kidney. Notably, all new compounds were more toxic than their cyclometallated precursor bearing two chlorido ligands, and the derivative bearing one phosphane ligand presented the most promising toxicity profile in our in vitro screening, displaying a p53 dependent activity in colorectal cancer HCT116 cells. Finally, for the first time (CN)-N-boolean AND cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance

The THESEUS space mission concept: science case, design and expected performances

THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1sr) with 0.5¿1 arcmin localization, an energy band extending from several MeV down to 0.3¿keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7¿m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late ¿20s/early ¿30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).© 2018 COSPARS.E. acknowledges the financial support from contracts ASI-INAF 1/009/10/0, NARO15 ASI-INAF 1/037/12/0 and ASI 2015-046-R.0. R.H. acknowledges GACR grant 13-33324S. S.V. research leading to these results has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 606176. D.S. was supported by the Czech grant 1601116S GA CR. Maria Giovanna Dainotti acknowledges funding from the European Union through the Marie Curie Action FP7-PEOPLE-2013-IOF, under grant agreement No. 626267 (>Cosmological Candles>)

The Large Observatory for x-ray timing

The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final down-selection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supra-nuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a WideField Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study

The LOFT mission concept: a status update

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, >8m2 effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Multimessenger Search for Sources of Gravitational Waves and High-Energy Neutrinos: Results for Initial LIGO-Virgo and IceCube

We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007-2010. These include parts of the 2005-2007 run and the 2009-2010 run for LIGO-Virgo, and IceCube's observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of $10^{-2}$\,M$_\odot$c$^2$ at $\sim 150$\,Hz with $\sim 60$\,ms duration, and high-energy neutrino emission of $10^{51}$\,erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below $1.6 \times 10^{-2}$\,Mpc$^{-3}$yr$^{-1}$. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era

Searches for continuous gravitational waves from nine young supernova remnants

We describe directed searches for continuous gravitational waves in data from the sixth LIGO science data run. The targets were nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One target's parameters are uncertain enough to warrant two searches, for a total of ten. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering F-statistic. We found no credible gravitational-wave signals. We set 95% confidence upper limits as strong (low) as $4\times10^{-25}$ on intrinsic strain, $2\times10^{-7}$ on fiducial ellipticity, and $4\times10^{-5}$ on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes.Comment: Science summary available at http://www.ligo.org/science/Publication-S6DirectedSNR/index.ph

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Catalytic Transformations of Alkynes via Ruthenium Vinylidene and Allenylidene Intermediates

NOTICE: This is the peer reviewed version of the following book chapter: Varela J. A., González-Rodríguez C., Saá C. (2014). Catalytic Transformations of Alkynes via Ruthenium Vinylidene and Allenylidene Intermediates. In: Dixneuf P., Bruneau C. (eds) Ruthenium in Catalysis. Topics in Organometallic Chemistry, vol 48, pp. 237-287. Springer, Cham. [doi: 10.1007/3418_2014_81]. This article may be used for non-commercial purposes in accordance with Springer Verlag Terms and Conditions for self-archiving.Vinylidenes are high-energy tautomers of terminal alkynes and they can be stabilized by coordination with transition metals. The resulting metal-vinylidene species have interesting chemical properties that make their reactivity different to that of the free and metal π-coordinated alkynes: the carbon α to the metal is electrophilic whereas the β carbon is nucleophilic. Ruthenium is one of the most commonly used transition metals to stabilize vinylidenes and the resulting species can undergo a range of useful transformations. The most remarkable transformations are the regioselective anti-Markovnikov addition of different nucleophiles to catalytic ruthenium vinylidenes and the participation of the π system of catalytic ruthenium vinylidenes in pericyclic reactions. Ruthenium vinylidenes have also been employed as precatalysts in ring closing metathesis (RCM) or ring opening metathesis polymerization (ROMP). Allenylidenes could be considered as divalent radicals derived from allenes. In a similar way to vinylidenes, allenylidenes can be stabilized by coordination with transition metals and again ruthenium is one of the most widely used metals. Metalallenylidene complexes can be easily obtained from terminal propargylic alcohols by dehydration of the initially formed metal-hydroxyvinylidenes, in which the reactivity of these metal complexes is based on the electrophilic nature of Cα and Cγ, while Cβ is nucleophilic. Catalytic processes based on nucleophilic additions and pericyclic reactions involving the π system of ruthenium allenylidenes afford interesting new structures with high selectivity and atom economy

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams