Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation

Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative pi-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C-H arylation. The functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Here the authors show a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts

3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo

Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases

Interface engineering of an electrospun nanofiber-based composite cathode for intermediate-temperature solid oxide fuel cells

Sluggish oxygen reduction reaction (ORR) kinetics are a major obstacle to developing intermediate-temperature solid-oxide fuel cells (IT-SOFCs). In particular, engineering the anion defect concentration at an interface between the cathode and electrolyte is important for facilitating ORR kinetics and hence improving the electrochemical performance. We developed the yttria-stabilized zirconia (YSZ) nanofiber (NF)-based composite cathode, where the oxygen vacancy concentration is controlled by varying the dopant cation (Y _2 O _3 ) ratio in the YSZ NFs. The composite cathode with the optimized oxygen vacancy concentration exhibits maximum power densities of 2.66 and 1.51 W cm ^−2 at 700 and 600 °C, respectively, with excellent thermal stability at 700 °C over 500 h under 1.0 A cm ^−2 . Electrochemical impedance spectroscopy and distribution of relaxation time analysis revealed that the high oxygen vacancy concentration in the NF-based scaffold facilitates the charge transfer and incorporation reaction occurred at the interfaces between the cathode and electrolyte. Our results demonstrate the high feasibility and potential of interface engineering for achieving IT-SOFCs with higher performance and stability

Activation of Persulfates by Graphitized Nanodiamonds for Removal of Organic Compounds

This study introduces graphited nanodiamond (G-ND) as an environmentally friendly, easy-to-regenerate, and cost-effective alternative catalyst to activate persulfate (i.e., peroxymonosulfate (PMS) and peroxydisulfate (PDS)) and oxidize organic compounds in water. The G-ND was found to be superior for persulfate activation to other benchmark carbon materials such as graphite, graphene, fullerene, and carbon nanotubes. The G-ND/persulfate showed selective reactivity toward phenolic compounds and some pharmaceuticals, and the degradation kinetics were not inhibited by the presence of oxidant scavengers and natural organic matter. These results indicate that radical intermediates such as sulfate radical anion and hydroxyl radical are not majorly responsible for this persulfate-driven oxidation of organic compounds. The findings from linear sweep voltammetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and electron paramagnetic resonance spectroscopy analyses suggest that the both persulfate and phenol effectively bind to G-ND surface and are likely to form charge transfer complex, in which G-ND plays a critical role in mediating facile electron transfer from phenol to persulfate. © 2016 American Chemical Societyclos

Chemo- and regioselective click reactions through nickel-catalyzed azide???alkyne cycloaddition

Metal-catalyzed cycloaddition is an expeditious synthetic route to functionalized heterocyclic frameworks. However, achieving reactivity-controlled metal-catalyzed azide-alkyne cycloadditions from competing internal alkynes has been challenging. Herein, we report a nickel-catalyzed [3 + 2] cycloaddition of unsymmetrical alkynes with organic azides to afford functionalized 1,2,3-triazoles with excellent regio- and chemoselectivity control. Terminal alkynes and cyanoalkynes afford 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles bearing a 4-cyano substituent, respectively. Thioalkynes and ynamides exhibit inverse regioselectivity compared with terminal alkynes and cyanoalkynes, affording 1,4,5-trisubstituted triazoles with 5-thiol and 5-amide substituents, respectively. Density functional theory calculations are performed for the elucidation of the reaction mechanism. The computed mechanism suggests that a nickellacyclopropene intermediate is generated by the oxidative addition of the alkyne substrate to the Ni(0)-Xantphos catalyst, and the subsequent C-N coupling of this intermediate with an azide is responsible for the chemo- and regioselectivity

Comparison of clinical manifestations in mpox patients living with HIV versus without HIV: a systematic review and meta-analysis

Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living with HIV are noted for an increased risk for severe symptoms; however, existing studies did not focus on the statistical comparison of mpox outcomes associated with HIV. Thus, we conducted a systematic review and meta-analysis to evaluate and compare the clinical manifestations of mpox in people living with HIV (PLWH) and people without HIV. In this systematic review and meta-analysis, PubMed/MEDLINE, Embase, and Google Scholar were searched up to March 7, 2023. A random effects model was used to calculate the pooled prevalence along with the 95% confidence intervals (CI), and the odds ratio and its corresponding 95% CIs were calculated to elucidate the significance of each clinical feature for mpox patients with and without HIV. In this study, we included 99 published papers with 2413 patients with mpox (median age, 35.5 years; PLWH n = 1151) from 27 countries across six continents. The odds ratio of the mpox outcomes with PLWH in comparison to patients without HIV was found to be significant for skin rash (1.24, 95% CI: 1.01–1.53), proctitis (2.03, 95% CI: 1.36–3.04), cough (0.57, 95% CI: 0.33–0.98), and diarrhea (3.85, 95% CI: 1.24–11.98). The odds ratio of mpox patients with HIV for historical infections of syphilis was 2.14 (95% CI: 1.38–3.32), compared with those without HIV. This is the first international and comprehensive study that performed a systematic review and meta-analysis to statistically measure mpox manifestations according to HIV status. As clinical features related to mucosal contact were characteristically pronounced in PLWH, our systematic review provides insight that the primary invasion site of infection strongly relates to the outcomes of mpox

Chemoselective Trifluoroethylation Reactions of Quinazolinones and Identification of Photostability

Herein, we report chemoselective trifluoroethylation routes of unmasked 2-arylquinazolin-4(3H)-ones using mesityl(2,2,2-trifluoroethyl)iodonium triflate at room temperature. Homologous C-, O-, and N-functionalized subclasses are accessed in a straightforward manner with a wide substrate scope. These chemoselective branching events are driven by Pd-catalyzed ortho-selective C???H activation at the pendant aryl ring and base-promoted reactivity modulation of the amide group, leveraging the intrinsic directing capability and competing pronucleophilicity of the quinazolin-4(3H)-one framework. Furthermore, outstanding photostability of the quinazolin-4(3H)-one family associated with nonradiative decay is presented

Synthesis of ??,??-unsaturated ketones through nickel-catalysed aldehyde-free hydroacylation of alkynes

??,??-Unsaturated ketones are common feedstocks for the synthesis of fine chemicals, pharmaceuticals, and natural products. Transition metal-catalysed hydroacylation reactions of alkynes using aldehydes have been recognised as an atom-economical route to access ??,??-unsaturated ketones through chemoselective aldehydic C???H activation. However, the previously reported hydroacylation reactions using rhodium, cobalt, or ruthenium catalysts require chelating moiety-bearing aldehydes to prevent decarbonylation of acyl-metal-hydride complexes. Herein, we report a nickel-catalysed anti-Markovnikov selective coupling process to afford non-tethered E-enones from terminal alkynes and S-2-pyridyl thioesters in the presence of zinc metal as a reducing agent. Utilization of a readily available thioester as an acylating agent and water as a proton donor enables the mechanistically distinctive and aldehyde-free hydroacylation of terminal alkynes. This non-chelation-controlled approach features mild reaction conditions, high step economy, and excellent regio- and stereoselectivity

Full-Hexacyanometallate Aqueous Redox Flow Batteries Exceeding 1.5 V in an Aqueous Solution

Aqueous redox flow batteries (RFBs) have attracted significant attention as energy storage systems by virtue of their inexpensive nature and long-lasting features. Although all-vanadium RFBs exhibit long lifetimes, the cost of vanadium resources fluctuates considerably, and is generally expensive. Iron-chromium RFBs take advantage of utilizing a low-cost and large abundance of iron and chromite ore; however, the redox chemistry of Cr-II/III generally involves strong Jahn-Teller effects. Herein, this work introduces a new Cr-based negolyte coordinated with strong-field ligands capable of mitigating strong Jahn-Teller effects, thereby facilitating low redox potential, high stability, and rapid kinetics. The balanced full-cell configuration features a stable lifetime of 500 cycles with energy density of 14 Wh L-1. With an excessive posolyte, the full-cell can attain a high energy density of 38.6 Wh L-1 as a single electron redox process. Consequently, the proposed system opens new avenues for the development of high-performance RFBs