763 research outputs found
Synthesis of 3,3-disubstituted heterocycles by Pd-catalyzed arylallylation of unactivated alkenes
Finding new methods of carbonâcarbon bond formation is a key goal in expanding current
methodology for heterocycle formation. Because of their inherently non-planar shape, new methods of
forming sp3-rich scaffolds are of particular importance. While there are methods for combining
heterocyclisation and formation of new sp3âsp3 carbonâcarbon bonds, these form the carbonâ
heteroatom bond rather than a carbonâcarbon bond of the heterocycle. Here we show a new alkene
arylallylation reaction that generates a heterocycle with concomitant formation of two new carbonâ
carbon bonds. Furthermore, we demonstrate that this process occurs through an isohypsic (redox
neutral) mechanism. Overall, this carboallylation reaction gives a new route to the synthesis of 3,3-
disubstituted heterocycles
Phonon-like hydrogen-bond modes in protic ionic liquids
Gigahertz- to terahertz-frequency infrared and Raman spectra contain a wealth of information concerning the structure, intermolecular forces, and dynamics of ionic liquids. However, these spectra generally have a large number of contributions ranging from slow diffusional modes to underdamped librations and intramolecular vibrational modes. This makes it difficult to isolate effects such as the role of Coulombic and hydrogen-bonding interactions. We have applied far-infrared and ultrafast optical Kerr effect spectroscopies on carefully selected ions with a greater or lesser degree of symmetry in order to isolate spectral signals of interest. This has allowed us to demonstrate the presence of longitudinal and transverse optical phonon modes and a great similarity of alkylammonium-based protic ionic liquids to liquid water. The data show that such phonon modes will be present in all ionic liquids, requiring a reinterpretation of their spectra
Catalytic Isohypsic-Redox Sequences for the Rapid Generation of C<sub>sp3</sub>-Containing Heterocycles
Crossâcoupling reactions catalyzed by transition metals are among the most influential in modern synthetic chemistry. The vast majority of transition metal catalyzed crossâcouplings rely on a catalytic cycle involving alternating oxidation and reduction of the metal center and are generally limited to forging just one type of new bond per reaction (e.g. the biaryl linkage formed during a Suzuki crossâcoupling). Here we present an IsohypsicâRedox Sequence (IRS) that uses one metal to effect two catalytic cycles, thereby generating multiple new types of bonds from a single catalyst source. We show that the IRS strategy is amenable to several widely used transformations including the SuzukiâMiyaura coupling, BuchwaldâHartwig amination, and Wacker oxidation. Furthermore, each of these reactions generates valueâadded heterocycles with significant sp3âC (3âdimensional) content. Our results provide a general framework for generating complex products by using a single metal to fulfill multiple roles. By uniting different combinations of reactions in the isohypsic and redox phases of the process, this type of catalytic multiple bondâforming platform has the potential for wide applicability in the efficient synthesis of functional organic molecules
Initial Technology Assessment for the Large-Aperture UV-Optical-Infrared (LUVOIR) Mission Concept Study
The NASA Astrophysics Division's 30-Year Roadmap prioritized a future large-aperture space telescope operating in the ultra-violet/optical/infrared wavelength regime. The Association of Universities for Research in Astronomy envisioned a similar observatory, the High Definition Space Telescope. And a multi-institution group also studied the Advanced Technology Large Aperture Space Telescope. In all three cases, a broad science case is outlined, combining general astrophysics with the search for biosignatures via direct-imaging and spectroscopic characterization of habitable exoplanets. We present an initial technology assessment that enables such an observatory that is currently being studied for the 2020 Decadal Survey by the Large UV/Optical/Infrared (LUVOIR) surveyor Science and Technology Definition Team. We present here the technology prioritization for the 2016 technology cycle and define the required technology capabilities and current state-of-the-art performance. Current, planned, and recommended technology development efforts are also reported
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High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis.
Mechanisms underpinning airway epithelial homeostatic maintenance and ways to prevent its dysregulation remain elusive. Herein, we identify that ÎČ-catenin phosphorylated at Y489 (p-ÎČ-cateninY489) emerges during human squamous lung cancer progression. This led us to develop a model of airway basal stem cell (ABSC) hyperproliferation by driving Wnt/ÎČ-catenin signaling, resulting in a morphology that resembles premalignant lesions and loss of ciliated cell differentiation. To identify small molecules that could reverse this process, we performed a high-throughput drug screen for inhibitors of Wnt/ÎČ-catenin signaling. Our studies unveil Wnt inhibitor compound 1 (WIC1), which suppresses T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) activity, reduces ABSC proliferation, induces ciliated cell differentiation, and decreases nuclear p-ÎČ-cateninY489. Collectively, our work elucidates a dysregulated Wnt/p-ÎČ-cateninY489 axis in lung premalignancy that can be modeled in vitro and identifies a Wnt/ÎČ-catenin inhibitor that promotes airway homeostasis. WIC1 may therefore serve as a tool compound in regenerative medicine studies with implications for restoring normal airway homeostasis after injury
Expression of synaptotagmin and syntaxin associated with N-type calcium channels in small cell lung cancer
AbstractThe presence of synaptic proteins involved in excitation/secretion coupling was examined in ten small cell lung cancer lines. N-Type calcium channels (Ï)-conotoxin receptors), synaptotagmin (p65) and syntaxin (HPC-1) were detected in eight. Co-immunoprecipitation experiments indicated that syntaxin can form a complex with synaptotagmin and calcium channels. The expression of synaptotagmin in small cell lung cancer may elicit an autoimmune response that reduces transmitter release at the nerve terminal
Effects of acute and repeated treatment with methocinnamox, a mu opioid receptor antagonist, on fentanyl self-administration in rhesus monkeys
Methocinnamox (MCAM), a mu opioid receptor antagonist with a long duration of action, attenuates heroin self-administration in rhesus monkeys, suggesting it could be an effective treatment for opioid use disorder (OUD). This study examined effects of acute and repeated MCAM administration on self-administration of the high-efficacy mu opioid receptor agonist fentanyl and characterized MCAM pharmacokinetics. Four rhesus monkeys self-administered i.v. infusions of fentanyl (0.00032âmg/kg/infusion) or cocaine (0.032âmg/kg/infusion). MCAM (0.1â0.32âmg/kg) or the opioid receptor antagonist naltrexone (0.001â0.032âmg/kg) was injected prior to test sessions to evaluate acute effects. On a separate occasion, 0.32âmg/kg MCAM was injected every 12 days for 5 total injections to evaluate the effectiveness of repeated treatment. Following acute injection, MCAM and naltrexone decreased fentanyl self-administration on the day of treatment, with attenuation lasting for up to 2 weeks after the larger MCAM dose and <1 day after naltrexone. Repeated MCAM administration decreased fentanyl self-administration for more than 2 months without altering cocaine self-administration. MCAM plasma concentrations peaked 15â45âmin after injection, with a half-life ranging from 13.7 to 199.8âmin, and decreased markedly 1 day after injection. MCAM selectively reduced opioid self-administration and remained effective with repeated administration. Moreover, MCAM was effective at times when plasma levels were very low, suggesting that pharmacodynamic (i.e., pseudoirreversible binding to mu opioid receptors) and not pharmacokinetic factors play a significant role in its long-lasting effects. Taken together with previous studies, these data indicate that MCAM could be a safe, effective, and long-acting treatment for OUD
The Far-Ultraviolet "Continuum" in Protoplanetary Disk Systems II: CO Fourth Positive Emission and Absorption
We exploit the high sensitivity and moderate spectral resolution of the
-Cosmic Origins Spectrograph to detect far-ultraviolet spectral features
of carbon monoxide (CO) present in the inner regions of protoplanetary disks
for the first time. We present spectra of the classical T Tauri stars HN Tau,
RECX-11, and V4046 Sgr, representative of a range of CO radiative processes. HN
Tau shows CO bands in absorption against the accretion continuum. We measure a
CO column density and rotational excitation temperature of N(CO) = 2 +/- 1
10 cm and T_rot(CO) 500 +/- 200 K for the absorbing gas.
We also detect CO A-X band emission in RECX-11 and V4046 Sgr, excited by
ultraviolet line photons, predominantly HI LyA. All three objects show emission
from CO bands at 1560 \AA, which may be excited by a combination
of UV photons and collisions with non-thermal electrons. In previous
observations these emission processes were not accounted for due to blending
with emission from the accretion shock, collisionally excited H, and
photo-excited H2; all of which appeared as a "continuum" whose components could
not be separated. The CO emission spectrum is strongly dependent upon the shape
of the incident stellar LyA emission profile. We find CO parameters in the
range: N(CO) 10 cm, T_{rot}(CO) > 300 K for the LyA-pumped
emission. We combine these results with recent work on photo- and
collisionally-excited H emission, concluding that the observations of
ultraviolet-emitting CO and H2 are consistent with a common spatial origin. We
suggest that the CO/H2 ratio in the inner disk is ~1, a transition between the
much lower interstellar value and the higher value observed in solar system
comets today, a result that will require future observational and theoretical
study to confirm.Comment: 12 pages, 7 figures, 3 tables. ApJ - accepte
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