Stereoselective Sequential Diels-Alder Reactions on a Cyclic Furan Trimer for the Construction of an Asymmetric Scaffold.

Multiple Diels-Alder reactions are a powerful method to construct large asymmetric scaffolds, but these reactions often produce numerous isomers. We now report a triple Diels-Alder reaction between a cyclic furan trimer and -substituted maleimides, achieving selective synthesis of a single asymmetric tris-adduct. The stereoselectivity of cycloaddition to π-extended furan derivatives was clarified by the experimental analysis of intermediates and theoretical calculations.

Silicon-aryl cooperative activation of ammonia.

Herein, we report the reactivity of N-heterocyclic carbene stabilized silylene-phosphinidene IDippPSi(TMS)SiTol (IDipp = 1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene) with ammonia, which results in an intermolecular 1,5-hydroamination and dearomatization of the NHC wingtip. DFT calculations reveal an unprecedented mechanism involving ammonia coordination to the silicon center, Meisenheimer-type complex formation, and a proton abstraction by the dearomatized aryl moiety.

Statistical analysis of feature-based molecular networking results from non-targeted metabolomics data.

Feature-based molecular networking (FBMN) is a popular analysis approach for liquid chromatography-tandem mass spectrometry-based non-targeted metabolomics data. While processing liquid chromatography-tandem mass spectrometry data through FBMN is fairly streamlined, downstream data handling and statistical interrogation are often a key bottleneck. Especially users new to statistical analysis struggle to effectively handle and analyze complex data matrices.

Isolation of a NHC-stabilized heavier nitrile and its conversion into an isonitrile analogue.

Nitriles (R-C≡N) have been investigated since the late eighteenth century and are ubiquitous encounters in organic and inorganic syntheses. In contrast, heavier nitriles, which contain the heavier analogues of carbon and nitrogen, are sparsely investigated species. Here we report the synthesis and isolation of a phosphino-silylene featuring an N-heterocyclic carbene-phosphinidene and a highly sterically demanding silyl group as substituents.

Cognitive and Histopathological Alterations in Rat Models of Early- and Late-Phase Memory Dysfunction: Effects of Sigma-1 Receptor Activation.

Background: Sigma-1 receptors are highly expressed in brain areas related to cognitive function and are a promising target for anti-amnesic treatments. We previously showed that activation of sigma-1 receptors by the selective agonist compound methyl(1 R,2 S/1 S,2 R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropane carboxylate [(±)-PPCC] promotes a remarkable recovery in rat models of memory loss associated to cholinergic dysfunction.

Objective: In this study, we sought to assess the role of (±)-PPCC on working memory deficits caused by noradrenergic depletion.

Depolarization of mouse DRG neurons by GABA does not translate into acute pain or hyperalgesia in healthy human volunteers.

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.

A neutral crystalline imino-substituted silyl radical.

The neutral three-coordinated imino(silyl)silyl radical was isolated from the reaction of N-heterocyclic iminosilicon tribromide (IBuN-SiBr) with NaSiBuMe. The radical was fully characterized by X-ray crystallography and electron paramagnetic resonance spectroscopy and supported by quantum chemical calculations.

Dietary iron intake has long-term effects on the fecal metabolome and microbiome.

Iron is essential for life, but its imbalances can lead to severe health implications. Iron deficiency is the most common nutrient disorder worldwide, and iron dysregulation in early life has been found to cause long-lasting behavioral, cognitive, and neural effects. However, little is known about the effects of dietary iron on gut microbiome function and metabolism.

Tetryliumylidene ions in synthesis and catalysis.

Tetryliumylidene ions ([R-E:]), recognised for their intriguing electronic properties, have attracted considerable interest. These positively charged species, with two vacant p-orbitals and a lone pair at the E(ii) centre (E = Si, Ge, Sn, Pb), can be viewed as the combination of tetrylenes (RE:) and tetrylium ions ([RE]), which makes them potent Lewis ambiphiles. Such electronic features highlight the potential of tetryliumylidenes for single-site small molecule activation and transition metal-free catalysis.

Orchid fruit and root movement analyzed using 2D photographs and a bioinformatics pipeline for processing sequential 3D scans.

Premise: Most studies of the movement of orchid fruits and roots during plant development have focused on morphological observations; however, further genetic analysis is required to understand the molecular mechanisms underlying this phenomenon. A precise tool is required to observe these movements and harvest tissue at the correct position and time for transcriptomics research.

Methods: We utilized three-dimensional (3D) micro-computed tomography (CT) scans to capture the movement of fast-growing roots, and built an integrated bioinformatics pipeline to process 3D images into 3D time-lapse videos.

Structural, Biochemical, and Bioinformatic Basis for Identifying Radical SAM Cyclopropyl Synthases.

The importance of radical S-adenosyl-l-methionine (RS) enzymes in the maturation of ribosomally synthesized and post-translationally modified peptides (RiPPs) continues to expand, specifically for the RS-SPASM subfamily. We recently discovered an RS-SPASM enzyme that installs a carbon-carbon bond between the geminal methyls of valine residues, resulting in the formation of cyclopropylglycine (CPG). Here, we sought to define the family of cyclopropyl (CP) synthases because of the importance of cyclopropane scaffolds in pharmaceutical development.

A neutral germanium-centred hard and soft lewis superacid and its unique reactivity towards hydrosilanes.

The germanium-centred Lewis superacid Ge(pin) (1) was isolated as acetonitrile mono-adduct 1·MeCN and thoroughly characterized by NMR spectroscopy, X-ray crystallography and quantum chemical calculations. Ion abstraction and NMR experiments revealed the hard as well as soft Lewis superacidic nature of 1·MeCN. The title compound readily activates hydrosilanes such as EtSiH, which is not feasible for its harder silicon homologue 2·MeCN, and even reacts with EtSiF.

Selective Noradrenaline Depletion in the Neocortex and Hippocampus Induces Working Memory Deficits and Regional Occurrence of Pathological Proteins.

Noradrenaline (NA) depletion occurs in Alzheimer's disease (AD); however, its relationship with the pathological expression of Tau and transactive response DNA-binding protein 43 (TDP-43), two major hallmarks of AD, remains elusive. Here, increasing doses of a selective noradrenergic immunotoxin were injected into developing rats to generate a model of mild or severe NA loss. At about 12 weeks post-lesion, dose-dependent working memory deficits were detected in these animals, associated with a marked increase in cortical and hippocampal levels of TDP-43 phosphorylated at Ser 409/410 and Tau phosphorylated at Thr 217.

Dearomatization of C Aromatic Hydrocarbons by Main Group Complexes.

The dearomatization reaction is a powerful method for transformation of simple aromatic compounds to unique chemical architectures rapidly in synthetic chemistry. Over the past decades, the chemistry in this field has evolved significantly and various important organic compounds such as crucial bioactive molecules have been synthesized through dearomatization. In general, photochemical conditions or assistance by transition metals are required for dearomatization of rigid arenes.

C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, -Linked Glycosylated Lipoxygenase.

Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of C/H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn ion as a spin probe.

Hippocampal Noradrenaline Is a Positive Regulator of Spatial Working Memory and Neurogenesis in the Rat.

Loss of noradrenaline (NA)-rich afferents from the Locus Coeruleus (LC) ascending to the hippocampal formation has been reported to dramatically affect distinct aspects of cognitive function, in addition to reducing the proliferation of neural progenitors in the dentate gyrus. Here, the hypothesis that reinstating hippocampal noradrenergic neurotransmission with transplanted LC-derived neuroblasts would concurrently normalize both cognitive performance and adult hippocampal neurogenesis was investigated. Post-natal day (PD) 4 rats underwent selective immunolesioning of hippocampal noradrenergic afferents followed, 4 days later, by the bilateral intrahippocampal implantation of LC noradrenergic-rich or control cerebellar (CBL) neuroblasts.

Storable Cell-Laden Alginate Based Bioinks for 3D Biofabrication.

Over the last decade, progress in three dimensional (3D) bioprinting has advanced considerably. The ability to fabricate complex 3D structures containing live cells for drug discovery and tissue engineering has huge potential. To realise successful clinical translation, biologistics need to be considered.

An Aluminum Telluride with a Terminal Al=Te Bond and its Conversion to an Aluminum Tellurocarbonate by CO Reduction.

Facile access to dimeric heavier aluminum chalcogenides [(NHC)Al(Tipp)-μ-Ch] (NHC=IiPr (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene, IMe (1,3,4,5-tetramethylimidazol-2-ylidene); Tipp=2,4,6-iPr C H ; Ch=Se, Te) by treatment of NHC-stabilized aluminum dihydrides with elemental Se and Te is reported. The higher affinity of IMe in comparison with IiPr toward the Al center in [(NHC)Al(Tipp)-μ-Ch] can be used for ligand exchange. Additionally, the presence of excess IMe allows for cleavage of the dimers to form a rare example of a neutral multiply bonded heavier aluminum chalcogenide in the form of a tetracoordinate aluminum complex, (IMe ) (Tipp)Al=Te.

Room Temperature Intermolecular Dearomatization of Arenes by an Acyclic Iminosilylene.

A novel nontransient acyclic iminosilylene (), bearing a bulky super silyl group (-SiBu) and -heterocyclic imine ligand with a methylated backbone, was prepared and isolated. The methylated backbone is the feature of that distinguishes it from the previously reported nonisolable iminosilylenes, as it prevents the intramolecular silylene center insertion into an aromatic C-C bond of an aryl substituent. Instead, exhibits an intermolecular Büchner-ring-expansion-type reactivity; the silylene is capable of dearomatization of benzene and its derivatives, giving the corresponding silicon analogs of cycloheptatrienes, .

Two Late Pleistocene human femora from Trinil, Indonesia: Implications for body size and behavior in Southeast Asia.

Late Pleistocene hominin postcranial specimens from Southeast Asia are relatively rare. Here we describe and place into temporal and geographic context two partial femora from the site of Trinil, Indonesia, which are dated stratigraphically and via Uranium-series direct dating to ca. 37-32 ka.

Room-Temperature-Observable Interconversion Between Si(IV) and Si(II) via Reversible Intramolecular Insertion Into an Aromatic C-C Bond.

An easily isolable silacycloheptatriene (silepin) 1 b was synthesized from the reaction of a N-heterocyclic imino (IPrN) substituted tribromosilane IPrNSiBr with the sterically congested bis(trimethylsilyl)triisopropylsilyl silanide KSi(TMS) Si( Pr) (BTTPS). In solution, the Si(IV) silepin 1 b is in a thermodynamic equilibrium with the acyclic Si(II) silylene 1 a. The relative concentration of the Si(II) or Si(IV) isomers can be controlled by temperature variation and observed by variable temperature NMR and UV/Vis spectroscopy.