This study presents an enantioselective oxidative cyclization of N-allyl carboxamides via a chiral triazole-substituted iodoarene catalyst. The method allows the synthesis of highly enantioenriched oxazolines and oxazines, with yields of up to 94% and enantioselectivities of up to 98% ee. Quaternary stereocenters can be constructed and, besides N-allyl amides, the corresponding thioamides and imideamides are well tolerated as substrates, giving rise to a plethora of chiral 5-membered N-heterocycles. By applying a multitude of further functionalizations, we finally demonstrate the high value of the observed chiral heterocycles as strategic intermediates for the synthesis of other enantioenriched target structures.Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.Dissociation of transthyretin (TTR) tetramers may lead to misfolding and aggregation of proamyloidogenic monomers, which underlies TTR amyloidosis (ATTR) pathophysiology. ATTR is a progressive disease resulting from the deposition of toxic fibrils in tissues that predominantly presents clinically as amyloid cardiomyopathy and peripheral polyneuropathy. Ligands that bind to and kinetically stabilize TTR tetramers prohibit their dissociation and may prevent ATTR onset. Drawing from clinically investigated AG10, we designed a constrained congener (14) that exhibits excellent TTR tetramer binding potency, prevents TTR aggregation in a gel-based assay, and possesses desirable pharmacokinetics in mice. Additionally, 14 significantly lowers murine serum retinol binding protein 4 (RBP4) levels despite a lack of binding at that protein's all-trans-retinol site. We hypothesize that kinetic stabilization of TTR tetramers via 14 is allosterically hindering all-trans-retinol-dependent RBP4-TTR tertiary complex formation and that the compound could present ancillary therapeutic utility for indications treated with RBP4 antagonists, such as macular degeneration.Uranium trioxide, UO3, has a T-shaped structure with bent uranyl, UO22+, coordinated by an equatorial oxo, O2-. The structure of cation UO3+ is similar but with an equatorial oxyl, O•-. Neutral and cationic uranium trioxide coordinated by nitrates were characterized by collision induced dissociation (CID), infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory. CID of uranyl nitrate, [UO2(NO3)3]- (complex A1), eliminates NO2 to produce nitrate-coordinated UO3+, [UO2(O•)(NO3)2]- (B1), which ejects NO3 to yield UO3 in [UO2(O)(NO3)]- (C1). Finally, C1 associates with H2O to afford uranyl hydroxide in [UO2(OH)2(NO3)]- (D1). IRMPD of B1, C1, and D1 confirms uranyl equatorially coordinated by nitrate(s) along with the following ligands (B1) radical oxyl O•-; (C1) oxo O2-; and (D1) two hydroxyls, OH-. As the nitrates are bidentate, the equatorial coordination is six in A1, five in B1, four in D1, and three in C1. Ligand congestion in low-coordinate C1 suggests orbital-directed bonding. Hydrolysis of the equatorial oxo in C1 epitomizes the inverse trans influence in UO3, which is uranyl with inert axial oxos and a reactive equatorial oxo. The uranyl ν3 IR frequencies indicate the following donor ordering O2-[best donor] ≫ O•-> OH-> NO3-.A novel approach for the asymmetric construction of polycyclic indazole skeletons via enamine-imine activation and PCET activation was developed by merging organocatalysis with photocatalysis through an asymmetric triple-reaction sequence. In this process, five C-X bonds and five consecutive chiral centers were efficiently constructed. Differently substituted polycyclic indazole deriatives were successfully constructed with satisfactory results under mild conditions.The design of metal-bearing carbon-based materials with unique structures and intriguing properties is highly desirable in the fields of physics, chemistry, and materials science. Here, within swarm-intelligence structure search and first-principles computations, we uncovered several hitherto unknown sodium carbides (i.e., Na4C, Na3C2, NaC, Na2C3, and NaC2) under high pressure. Intriguingly, the C atom arrangement reveals multiple structure evolution behavior with increased carbon content, from isolated anions in Na4C, tetramers in Na3C2, extended chains in NaC, pentagonal rings in Na2C3, to eventually hexagonal rings in NaC2. Among predicted phases, the superconducting critical temperature Tc of NaC2 could approach ∼42 K at 80 GPa, which is slightly higher than the Tc of 39 K in the highest phonon-mediated superconductivity of MgB2 at ambient pressure. This work offers insights into the reaction of carbides containing alkali metals and paves the way for the future investigation of high superconductivity in metal carbide systems.Oxygen atoms on transition metal surfaces are highly mobile under the demanding pressures and temperatures typically employed for heterogeneously catalyzed oxidation reactions. This mobility allows for rapid surface diffusion of oxygen atoms, as well as absorption into the subsurface and reemergence to the surface, resulting in variable reactivity. Subsurface oxygen atoms play a unique role in the chemistry of oxidized metal catalysts, yet little is known about how subsurface oxygen is formed or returns to the surface. https://www.selleckchem.com/products/ins018-055-ism001-055.html Furthermore, if oxygen diffusion between the surface and subsurface is mediated by defects, there will be localized changes in the surface chemistry due to the elevated oxygen concentration near the emergence sites. We observed that oxygen atoms emerge preferentially along the boundary between surface phases and that subsurface oxygen is depleted before the surface oxide decomposes.