C4-C5 fused pyrazol-3-amines: when the degree of unsaturation and electronic characteristics of the fused ring controls regioselectivity in Ullmann and acylation reactions

Pyrazol-3-amine is a scaffold present in a large number of compounds with a wide range of biological activities and, in many cases, the heterocycle is C4-C5 fused to a second ring. Among the different reactions used for the decoration of the pyrazole ring, Ullmann and acylation have been widely applied. However, there is some confusion in the literature regarding the regioselectivity of such reactions (substitution at N1 or N2 of the pyrazole ring) and no predictive rule has been so far established. As a part of our work on 3-amino-pyrazolo[3,4-b]pyridones 13, we have studied the regioselectivity of such reactions in different C4-C5 fused pyrazol-3-amines. As a rule of thumb, the Ullmann and acylation reactions take place, predominantly, at the NH and non-protonated nitrogen atom of the pyrazole ring respectively, of the most stable initial tautomer (1H- or 2H-pyrazole), which can be easily predicted by using DFT calculations

Proton drip-line nuclei in Relativistic Hartree-Bogoliubov theory

Ground-state properties of spherical even-even nuclei $14\leq Z \leq 28$ and $N=18,20,22$ are described in the framework of Relativistic Hartree Bogoliubov (RHB) theory. The model uses the NL3 effective interaction in the mean-field Lagrangian, and describes pairing correlations by the pairing part of the finite range Gogny interaction D1S. Binding energies, two-proton separation energies, and proton $rms$ radii that result from fully self-consistent RHB solutions are compared with experimental data. The model predicts the location of the proton drip-line. The isospin dependence of the effective spin-orbit potential is discussed, as well as pairing properties that result from the finite range interaction in the $pp$ channel.Comment: 12 pages, RevTex, 10 p.s figures, submitted to Phys. Rev.

An Unequivocal Synthesis of 2-Aryl Substituted 3-Amino-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-ones

The reaction between pyridones (1) and substituted hydrazines 4 can afford two different regioisomeric pyrazolo[3,4-b]pyridin - 6-ones 2 and 3 depending on the initial substitution of the methoxy group and the direction of the cyclization. In the case of phenylhydrazine 4 (R3 = Ph), we have clearly shown that the treatment of pyridones 1a-d with 4 (R3 = Ph) in MeOH at temperatures below 1408C yields, independently of the nature and position of the substituents present in the pyridone ring, the open intermediates 7a-d. When the reaction is carried at 1408C under microwave irradiation, the corresponding 2-aryl substituted pyrazolo[3,4-b]pyridines 3a-d are always formed. We have experimentally determined, using DSC techniques, the activation energies of the two steps involved in the formation of 3: a) substitution of the methoxy group present in pyridones 1 with phenylhydrazine 4 (R3 = Ph) to afford intermediates 7 and b) cyclization of intermediates 7 to yield pyrazolopyridines 3. The results obtained, 15 and 42 kcal·mol 1 respectively, are in agreement with the experimental findings

Proton drip-line nuclei in relativistic mean-field theory

The position of the two-proton drip line has been calculated for even-even nuclei with $10 \leq Z \leq 82$ in the framework of the relativistic mean-field (RMF) theory. The current model uses the NL3 effective interaction in the mean-field Lagrangian and describes pairing correlations in the Bardeen-Cooper-Schrieffer (BCS) formalism. The predictions of the RMF theory are compared with those of the Hartree-Fock+BCS approach (with effective force Skyrme SIII) and the finite-range droplet model (FRDM) and with the available experimental information.Comment: 18 pages, RevTeX, 2 p.s figures, to appear in Phys. Rev.

Genomics and metagenomics of trimethylamine-utilizing Archaea in the human gut microbiome

International audienceThe biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation

A Cherenkov imager for charge measurements of Nuclear Cosmic Rays in the CREAM II instrument

A proximity focusing Cherenkov imager for the charge measurement of nuclear cosmic rays in the CREAM II instrument, called CHERCAM, is under construction. This imager consists of a silica aerogel radiator plane facing a detector plane equipped with standard photomultipliers. The two planes are separated by a minimal ring expansion gap. The Cherenkov light yield is proportional to the squared charge of the detected particle. The expected relative light collection accuracy is in the few percents range. It should lead to single element separation over the range of nuclear charge Z of main interest 1 $leq$ Z $<$\approx$ 26

A possible association of the new VHE gamma-ray source HESS J1825--137 with the pulsar wind nebula G18.0--0.7

We report on a possible association of the recently discovered very high-energy $\gamma$-ray source HESS J1825--137 with the pulsar wind nebula (commonly referred to as G 18.0--0.7) of the $2.1\times 10^{4}$ year old Vela-like pulsar PSR B1823--13. HESS J1825--137 was detected with a significance of 8.1 $\sigma$ in the Galactic Plane survey conducted with the H.E.S.S. instrument in 2004. The centroid position of HESS J1825--137 is offset by 11\arcmin south of the pulsar position. \emph{XMM-Newton} observations have revealed X-ray synchrotron emission of an asymmetric pulsar wind nebula extending to the south of the pulsar. We argue that the observed morphology and TeV spectral index suggest that HESS J1825--137 and G 18.0--0.7 may be associated: the lifetime of TeV emitting electrons is expected to be longer compared to the {\it XMM-Newton} X-ray emitting electrons, resulting in electrons from earlier epochs (when the spin-down power was larger) contributing to the present TeV flux. These electrons are expected to be synchrotron cooled, which explains the observed photon index of $\sim 2.4$, and the longer lifetime of TeV emitting electrons naturally explains why the TeV nebula is larger than the X-ray size. Finally, supernova remnant expansion into an inhomogeneous medium is expected to create reverse shocks interacting at different times with the pulsar wind nebula, resulting in the offset X-ray and TeV $\gamma$-ray morphology.Comment: 5 pages, 3 figures, to appear in Astronomy and Astrophysics Letter

First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula

The Vela supernova remnant (SNR) is a complex region containing a number of sources of non-thermal radiation. The inner section of this SNR, within 2 degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from an extended region to the south of the pulsar, within an integration region of radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36' J2000.0). The excess coincides with a region of hard X-ray emission seen by the ROSAT and ASCA satellites. The observed energy spectrum of the source between 550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45 +/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/- 2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17 (stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear measurement of a peak in the spectral energy distribution from a VHE gamma-ray source, likely related to inverse Compton emission. A fit of an Inverse Compton model to the H.E.S.S. spectral energy distribution gives a total energy in non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a distance of 290 parsec to the pulsar. The best fit electron power law index is 2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and Astrophysics letter

3.9 day orbital modulation in the TeV gamma-ray flux and spectrum from the X-ray binary LS 5039

New observations of LS 5039, a High Mass X-ray Binary comprising a massive star and compact object, were carried out with the High Energy Stereoscopic System of Cherenkov Telescopes (H.E.S.S.) in 2005 at very high energy (VHE) gamma-ray energies. These observations reveal that its flux and energy spectrum are modulated with the 3.9 day orbital period of the binary system. This is the first time in gamma-ray astronomy that orbital modulation has been observed, and periodicity clearly established using ground-based gamma-ray detectors. The VHE gamma-ray emission is largely confined to half of the orbit, peaking around the inferior conjunction epoch of the compact object. For this epoch, there is also a hardening of the energy spectrum in the energy range between 0.2 TeV and a few TeV. The flux vs. orbital phase profile provides the first clear indication of gamma-ray absorption via pair production within an astrophysical source, a process which is expected to occur if the gamma-ray production site is situated within ~1 AU of the compact object. Moreover the production region size must be not significantly greater than the binary separation (~0.15 AU). Notably, these constraints are also considerably smaller than the collimated outflows or jets (extending out to ~1000 AU) observed in LS 5039. The spectral hardening could arise from variations with phase in the maximum electron energies, and/or the dominant VHE gamma-ray production mechanism.Comment: 8 pages, 8 figures, accepted for publication in Astronomy & Astrophysic

H.E.S.S. observations of gamma-ray bursts in 2003-2007

Very-high-energy (VHE; >~100 GeV) gamma-rays are expected from gamma-ray bursts (GRBs) in some scenarios. Exploring this photon energy regime is necessary for understanding the energetics and properties of GRBs. GRBs have been one of the prime targets for the H.E.S.S. experiment, which makes use of four Imaging Atmospheric Cherenkov Telescopes (IACTs) to detect VHE gamma-rays. Dedicated observations of 32 GRB positions were made in the years 2003-2007 and a search for VHE gamma-ray counterparts of these GRBs was made. Depending on the visibility and observing conditions, the observations mostly start minutes to hours after the burst and typically last two hours. Results from observations of 22 GRB positions are presented and evidence of a VHE signal was found neither in observations of any individual GRBs, nor from stacking data from subsets of GRBs with higher expected VHE flux according to a model-independent ranking scheme. Upper limits for the VHE gamma-ray flux from the GRB positions were derived. For those GRBs with measured redshifts, differential upper limits at the energy threshold after correcting for absorption due to extra-galactic background light are also presented.Comment: 9 pages, 4 tables, 3 figure