Alumanyl-Samarium(II): Synthesis, Characterization, and Reactivity Studies.

Metal-metal bonded species involving lanthanides are intriguing but rare. The recently reported salt metathesis reaction of an Al anion and SmI2(thf)2 yields novel heterometallic compound possessing two distinctive Al-Sm bonds. Although the Al-Sm bonds were considerably long [3.518(1) and 3.543(1) Å], DFT calculations indicated polar character of the Alδ--Smδ+ bonds. This is the first example of lanthanide species containing X-type Al ligands. Reactivity studies have demonstrated that the introduction of Sm(II) produces unique reactivity. The reaction with carbodiimide led to an insertion of carbodiimide into the Al-Sm bonds and reductive coupling of carbodiimide to create an oxalamidinate moiety, facilitated by Sm(II). Exposure of the Al-Sm-Al complex toward ethylene furnished a Sm(II) salt of anionic aluminacyclopropane that was spontaneously isomerized to a 1,4-dialuminacyclohexane derivative. The important role of Sm(II) to facilitate the ring expansion through an alkyl-relay mechanism was elucidated by DFT calculations.

Vanadium Alumanyl Complex: Synthesis, Characterization, Reactivity, and Application as a Catalyst for C-H Alumanylation of Alkenes.

A complex containing a V-Al bond is described. This species can be prepared by either transmetalation of a previously disclosed alumanylpotassium with Cp2VCl or photolytic oxidative alumination of Cp2V using the corresponding dialumane. Reaction of the resulting V-Al complex with H2 gave a Cp2V-dihydridoaluminate complex. These complexes were studied with X-ray crystallography, vanadium K-edge XANES spectroscopy, and DFT calculations. Finally, the reactivity of these molecules was studied opening the way to a catalytic C-H alumanylation of alkenes.

Base-Stabilized Gallium Sulfides and Selenides Supported by a Bis(oxazolinyl)(phenyl)methanide Ligand.

Gallylene supported by a bis(oxazolinyl)(phenyl)methanide (Boxm) ligand was synthesized and structurally characterized. The reaction of this gallylene with triphenylphosphine sulfide/selenide yielded dimeric gallium sulfide and selenide. These compounds could be converted to monomeric terminal sulfide and selenide by coordination of an external Lewis base such as an N-heterocyclic carbene (NHC or IMe4) and 4-dimethylaminopyridiene (DMAP). These doubly-base-stabilized gallium sulfide/selenide reacted with phenyl isocyanate to give the corresponding cycloadducts by releasing the Lewis base, indicating the formation of a single-base-stabilized gallium sulfide/selenide intermediate.

Mechanochemical Synthesis of Non-Solvated Dialkylalumanyl Anion and XPS Characterization of Al(I) and Al(II) Species.

A non-solvated alkyl-substituted Al(I) anion dimer was synthesized by a reduction of haloalumane precursor using a mechanochemical method. The crystallographic and theoretical analysis revealed its structure and electronic properties. Experimental XPS analysis of the Al(I) anions with reference compounds revealed the lower Al 2p binding energy corresponds to the lower oxidation state of Al species. It should be emphasized that the experimentally obtained XPS binding energies were reproduced by delta SCF calculations and were linearly correlated with NPA charges and 2p orbital energies.

Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis.

OBJECTIVES: Prevotella copri is considered to be a contributing factor in rheumatoid arthritis (RA). However, in some non-Westernised countries, healthy individuals also harbour an abundance of P. copri in the intestine. This study investigated the pathogenicity of RA patient-derived P. copri (P. copri RA) compared with healthy control-derived P. copri (P. copri HC). METHODS: We obtained 13 P. copri strains from the faeces of patients with RA and healthy controls. Following whole genome sequencing, the sequences of P. copri RA and P. copri HC were compared. To analyse the arthritis-inducing ability of P. copri, we examined two arthritis models (1) a collagen-induced arthritis model harbouring P. copri under specific-pathogen-free conditions and (2) an SKG mouse arthritis model under P. copri-monocolonised conditions. Finally, to evaluate the ability of P. copri to activate innate immune cells, we performed in vitro stimulation of bone marrow-derived dendritic cells (BMDCs) by P. copri RA and P. copri HC. RESULTS: Comparative genomic analysis revealed no apparent differences in the core gene contents between P. copri RA and P. copri HC, but pangenome analysis revealed the high genome plasticity of P. copri. We identified a P. copri RA-specific genomic region as a conjugative transposon. In both arthritis models, P. copri RA-induced more severe arthritis than P. copri HC. In vitro BMDC stimulation experiments revealed the upregulation of IL-17 and Th17-related cytokines (IL-6, IL-23) by P. copri RA. CONCLUSION: Our findings reveal the genetic diversity of P. copri, and the genomic signatures associated with strong arthritis-inducing ability of P. copri RA. Our study contributes towards elucidation of the complex pathogenesis of RA.

Base-Stabilized Neutral Oxoborane and Thioxoborane Supported by a Bis(oxazolinyl)(phenyl)methanide Ligand.

Base-stabilized neutral oxoborane and thioxoborane supported by a bis(oxazolinyl)(phenyl)methanide ligand have been synthesized and structurally characterized. While previous synthetic attempts of oxoborane ligated by ß-diketiminate (NacNac) did not allow for its isolation in acid-free form, oxoborane supported by a bis(oxazolinyl)(phenyl)methanide ligand is isolable, due to the absence of imine ɑ-protons and steric protection of enamine carbon. Crystallographic analysis revealed the presence of a B-O double bond close to the shortest end of the reported lengths. Its reactivity has also been examined, and it was majorly governed by the nucleophilicity and basicity of the oxygen atom. The chemical inertness and synthetic convenience of the bis(oxazolinyl)(phenyl)methanide scaffold presented in this work suggest its utility as an innocent alternative to the NacNac scaffold.

Reactions of Tetra(o-tolyl)diborane(4) with Organic Azides: Formation of Fluorescent Boron-Fused Hexazenes.

The reaction of tetra(o-tolyl)diborane(4) with organic azides afforded three different compounds, diborylamines, diboryltriazenes, and B2 -hexazenes having a bicyclic B2 N6 ring system. The reaction with aryl azides gave diborylamines, while the reaction with 1 equiv. of alkyl azides furnished diboryltriazenes. In the case of the reaction with an excess amount of primary alkyl azide, a new heterocyclic B2 -hexazenes were obtained. The formation of the B2 N6 structure could be explained by one general reaction mechanism via the diboryltriazene intermediate according to the control experiments and DFT calculations. The B2 -hexazenes exhibited a strong fluorescence with a remarkably high fluorescent quantum yield of up to 96 %.

Alkali Chloride Adducts of Acyclic Acylaluminum: Synthesis, Structure, and Reactivity Studies.

Two acyclic acylaluminums and one cyclic acylaluminum dimer were synthesized by reaction of the recently reported Al-anion with acyl chloride. The reaction of the acylaluminums with TMSOTf and DMAP gave a ring-expanded iminium-substituted aluminate and a 2-C-H cleaved product. In the reaction of acylaluminums toward C=O and C=N bonds, acyclic acylaluminums reacted as an acyl nucleophile, while the cycilc dimer showed no reactivity. Amide-bond forming ligation using acyclic acylaluminums and hydroxylamines was further demonstrated. Throughout the study, acyclic acylaluminums exhibited higher reactivity than that of the cyclic dimer.

A Tetraorganyl-Alumaborane with An Al-B σ-Bond and Two Adjacent Lewis-Acidic Centers.

A tetraorganyl-alumaborane (3) that contains an Al-B bond and twisted Al and B planes was synthesized and structurally characterized. UV-vis absorption spectroscopy, electrochemical measurement, and DFT calculations were employed to reveal the electronic properties of 3. The reactivity of 3 toward DMSO and CO was studied to demonstrate its deoxygenating abilities. On the basis of the results of the DFT calculations, a detailed reaction mechanism was developed, which highlighted the important role of the distinct Lewis acidity of the group-13 elements Al and B in 3.

Al-Sc Bonded Complexes: Synthesis, Structure, and Reaction with Benzene in the Presence of Alkyl Halide.

An alumanyl anion possessing N,N'-bis(2,6-diisopropylphenyl)-1,3-propanediamine ligand was synthesized and characterized. Transmetalation of this Al anion with diaminoscandium chloride precursors afforded the corresponding Al-Sc complexes possessing an unprecedented Al-Sc bond. The Al-Sc[N(SiMe3)2] complex underwent intramolecular C-H cleavage to form a bridged dinuclear complex with µ-hydrido and µ-methylene ligands. The Al-Sc(NiPr2)2 complex reacted with benzene in the presence of alkyl bromide to furnish a 1,4-dialuminated cyclohexadiene product with a concomitant formation of the alkyl-alkyl coupled product. Although the latter product seems to form through the radical mechanism, DFT calculations revealed an ionic mechanism involving bimetallic reaction pathways to react with alkyl bromide and benzene, which provides new insight into the chemistry of metal-metal bonded compounds.

Rhodium-Catalyzed Acrylate Synthesis from Carbon Dioxide and Ethylene by using a Guanidine-Based Pincer Ligand: Perturbing Occupied d-Orbitals by pπ-dπ Repulsion Makes a Difference.

Rhodium-catalyzed acrylate synthesis from CO2 and ethylene was accomplished by using a guanidine-based NCN pincer ligand. The repulsion between pπ-electron of guanidine sidearms and occupied dπ orbital of rhodium center raised the level of d-electrons close to those of formerly known d8 -ruthenium catalyst, thereby promoting the metallalactone formation from carbon dioxide and ethylene. This work fills the absence of group-9 metal based catalyst for the acrylate synthesis and provides a designing approach for pincer-ligated d8 -metal catalysts to utilize pπ-dπ interaction for promoting desirable redox processes.

Cardiopulmonary exercise testing for patients with anorexia nervosa: a case-control study.

PURPOSE: Patients with anorexia nervosa (AN) require appropriate nutrient therapy and physical activity management. Eating disorder treatment guidelines do not include safe, evidence-based intensity criteria for exercise. This study used cardiopulmonary exercise testing (CPX) to evaluate the exercise tolerance of patients with AN. METHODS: CPX was performed with 14 female patients with AN admitted to a specialized eating disorder unit between 2015 and 2019. Their anaerobic threshold (AT) was determined by assessing their exercise tolerance using CPX and compared with 14 healthy controls (HC). The metabolic equivalents (AT-METS) were compared when AT was reached. We examined factors related to AT (AN-AT) in the AN group, including age, body mass index (BMI), previous lowest weight, minimum BMI, past duration of BMI < 15, exercise history, and ΔHR (heart rate at the AT-resting heart rate). RESULTS: The AT of the AN group (BMI: 15.7 [Mean] ± 1.8 standard deviation [SD]) was significantly lower than that of the HC group (BMI: 19.7 ± 1.8) (AN: 10.0 ± 1.8 vs. HC: 15.2 ± 3.0 ml/kg/min, P < 0.001). AT-METS was also significantly lower in the AN group than in the HC group (AN: 2.9 ± 0.52 vs. HC: 4.4 ± 0.91, P < 0.001). AN-AT was highly influenced by ΔHR. CONCLUSIONS: This study showed that AT and AT-METS were lower in patients with AN than in HC. Patients with AN should be prescribed light-intensity aerobic exercise, and the current findings may help develop future physical management guidelines for patients with AN. LEVEL OF EVIDENCE: III: Evidence obtained from case-control analytic studies.

Isomerization of a cis-(2-Borylalkenyl)Gold Complex via a Retro-1,2-Metalate Shift: Cleavage of a C-C/C-Si Bond trans to a C-Au Bond.

This manuscript describes the first example of an alkyne insertion to the Au-B bond of a di(o-tolyl)borylgold complex to afford a cis-2-borylalkenylgold complex, and its isomerization to result in interchanging substituents on the alkenyl carbon atom and the boron atom. The former reaction is the first example of an alkyne insertion to a Au-B bond. In the latter reaction, the regiochemistry of the isomerized alkenylgold products varied depending on the substituents. DFT calculations revealed the formation of gold alkynylborates as a common intermediate via a "retro-1,2-metalate shift", which can be considered as an anti-ß-carbon/silicon elimination, and identified a subsequent 1,2-metalate shift as the regiochemistry-determining step. Relative energies of the transition states to each isomer and natural-bond-orbital (NBO) analyses were used to clearly rationalize the regiochemistry of the products.

An Alumanylyttrium Complex with an Absorption due to a Transition from the Al-Y Bond to an Unoccupied d-Orbital.

The reaction between a dialkyl-substituted alumanyl anion and [Y(CH2 SiMe3 )2 (thf)3 ][BPh4 ] resulted in the formation of (dialkylalumanyl)yttrium complex 2, which exhibits the first 2-center-2-electron (2 c-2 e) Al-Y bond. The 1 H and 13 C NMR spectra of 2 together with an X-ray crystallographic analysis indicated a C2v symmetrical structure. DFT calculations on 2 revealed that its LUMO consists of overlapping 3 p- and 4 d-orbitals of the Al and Y atoms, respectively, and that the HOMO-LUMO gap is narrow. The UV/Vis spectrum of 2 exhibited a visible absorption at 432 nm, which suggests that the strong σ-donating and π-accepting character of the three-coordinate dialkylalumanyl ligand generates a colored d0 -complex that does not contain any π-electrons.

Cycloaddition of Dialkylalumanyl Anion toward Unsaturated Hydrocarbons in (1+2) and (1+4) Modes.

The reactivity of dialkylalumanyl anion (1) towards naphthalene, anthracene, diphenylacetylene, and (E)/(Z)-stilbenes was investigated. The compound 1 reacts with naphthalene and anthracene through (1+4) cyclization, giving Al-containing norbornadiene derivatives. In the reaction of 1 with diphenylacetylene and (E)/(Z)-stilbenes, (1+2) cyclization proceeded to form Al-C-C three-membered rings. Cyclization toward (E)- or (Z)-stilbenes solely gave a trans-cycloadduct. DFT calculations revealed that the cycloaddition of 1 with (Z)-stilbene proceeds via a single transition state with a carbanion character, which results in the selectivity towards the trans-cycloadduct.

A meta-Selective C-H Alumination of Mono-Substituted Benzene by Using An Alkyl-Substituted Al Anion through Hydride-Eliminating SN Ar Reaction.

Reaction of an Al-centered anion with toluene proceeded to form C-H cleaved product with a perfect meta-selectivity and a relatively small kinetic isotope effect (KIE, kH /kD =1.51). DFT calculations suggested a two-step reaction mechanism and electronically controlled meta-selectivity arising from the electron-donating methyl group. The reaction with other mono-substituted arenes was also investigated.

Efficacy of laninamivir octanoate in mice with advanced inflammation stage caused by infection of highly lethal influenza virus.

Four neuraminidase (NA) inhibitors and an RNA synthesis inhibitor were recently approved and are currently in clinical use for influenza. Among NA inhibitors, oseltamivir phosphate (OSE, Tamiflu®) and zanamivir are approved worldwide, whereas peramivir and laninamivir octanoate (LAN, Inavir®) are regionally approved for human use. Therefore, OSE has been used to treat infections of highly pathogenic influenza viruses, such as H5N1 and H7N9, which caused epidemic in southeast Asia and Egypt, and China, respectively. Generally, OSE is administered twice daily for 5 days by oral administration, and LAN once by inhalation for completing influenza therapy. In this study, we compared the efficacy of OSE and LAN administered according to the regimens in mice infected with highly lethal influenza viruses. The drugs were administered at the early and late stages of infection, which correspond to mild and severe inflammation in the lungs, respectively. Based on the drugs' regimens for human, a single administration of LAN at both stages of inflammation showed superior efficacy to repeated administration of OSE. LAN, as in OSE, could also be efficacious in treating severe influenza in humans.

Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus.

Background: Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Methods: Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof. Results: Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Conclusions: Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.

Reactivity of a Tetra(o-tolyl)diborane(4) Dianion as a Diarylboryl Anion Equivalent.

Lithium and magnesium salts of tetra(o-tolyl)diborane(4) dianion, having B=B double bond character, were synthesized. It was clarified that the lithium salt of the dianion has a high-lying HOMO and a narrow HOMO-LUMO gap, which were perturbed by dissociation of Li+ cation, as judged by UV/Vis spectroscopy and DFT calculations. The lithium salt of the dianion reacted as two equivalents of a diarylboryl anion with CH2 Cl2 or S8 to give boryl-substituted products.

A Monomeric Stannabenzene: Synthesis, Structure, and Electronic Properties.

A tin-containing benzene, stannabenzene, was synthesized and isolated as a monomeric form. The X-ray crystallographic analysis revealed the planar structure of the stannabenzene ring and unsaturated Sn-C and C-C bonds without bond alternation. Low-field shifted NMR signals and negative nuclear-independent chemical shifts (NICS) values are in agreement with the features of aromatic compounds. The narrow HOMO-LUMO gap of stannabenzene has been revealed by UV/Vis spectroscopy and electrochemistry.