Reusable Manganese Catalyst for Site-Selective Pyridine C-H Arylations and Alkylations.

Herein, we disclose a recyclable, hybrid manganese catalyst for site-selective azine C-H activation by weak amide assistance. The novel, reusable catalyst enabled C3-H arylation and C3-H alkylation with ample scope, and was characterized by detailed transmission electron microscopy analysis.

C-H activation by immobilized heterogeneous photocatalysts.

During the last decades, the merger of photocatalysis with transition metal chemistry has been surfaced as a sustainable tool in modern molecular syntheses. This Account highlights major advances in synergistic photo-enabled C‒H activations. Inspired by our homogenous ruthenium- and copper-catalyzed C‒H activations in the absence of an exogenous photosensitizer, this Account describes the recent progress on heterogeneous photo-induced C‒H activation enabled by immobilized hybrid catalysts until September 2021, with a topical focus on recyclability as well as robustness of the heterogeneous photocatalyst.

A Strategy for Site- and Chemoselective C-H Alkenylation through Osmaelectrooxidative Catalysis.

Herein, we disclose osmaelectrocatalyzed C-H activations that set the stage for electrooxidative alkyne annulations by benzoic acids. The osmium electrocatalysis enables site- and chemoselective electrooxidative C-H activations with unique levels of selectivity. The isolation of unprecedented osmium(0) and osmium(II) intermediates, along with crystallographic characterization and analyses by spectrometric and spectroscopic in operando techniques delineate a synergistic osmium redox catalyst regime. Detailed mechanistic studies revealed a facile C-H cleavage, which allows for an ample substrate scope, providing provide robust and user-friendly access to annulated heterocycles.

Photoinduced Heterogeneous C-H Arylation by a Reusable Hybrid Copper Catalyst.

Heterogeneous copper catalysis enabled photoinduced C-H arylations under exceedingly mild conditions at room temperature. The versatile hybrid copper catalyst provided step-economical access to arylated heteroarenes, terpenes and alkaloid natural products with various aryl halides. The hybrid copper catalyst could be reused without significant loss of catalytic efficacy. Detailed studies in terms of TEM, HRTEM and XPS analysis of the hybrid copper catalyst, among others, supported its outstanding stability and reusability.

Recyclable Ruthenium Catalyst for Distal meta-C-H Activation.

We disclose the unprecedented hybrid-ruthenium catalysis for distal meta-C-H activation. The hybrid-ruthenium catalyst was recyclable, as was proven by various heterogeneity tests, and fully characterized with various microscopic and spectroscopic techniques, highlighting the physical and chemical stability. Thereby, the hybrid-ruthenium catalysis proved broadly applicable for meta-C-H alkylations of among others purine-based nucleosides and natural product conjugates. Additionally, its versatility was further reflected by meta-C-H activations through visible-light irradiation, as well as para-selective C-H activations.

C7-Indole Amidations and Alkenylations by Ruthenium(II) Catalysis.

C7-H-functionalized indoles are ubiquitous structural units of biological and pharmaceutical compounds for numerous antiviral agents against SARS-CoV or HIV-1. Thus, achieving site-selective functionalizations of the C7-H position of indoles, while discriminating among other bonds, is in high demand. Herein, we disclose site-selective C7-H activations of indoles by ruthenium(II) biscarboxylate catalysis under mild conditions. Base-assisted internal electrophilic-type substitution C-H ruthenation by weak O-coordination enabled the C7-H functionalization of indoles and offered a broad scope, including C-N and C-C bond formation. The versatile ruthenium-catalyzed C7-H activations were characterized by gram-scale syntheses and the traceless removal of the directing group, thus providing easy access to pharmaceutically relevant scaffolds. Detailed mechanistic studies through spectroscopic and spectrometric analyses shed light on the unique nature of the robust ruthenium catalysis for the functionalization of the C7-H position of indoles.

Bimetallic Cobalt-Rhodium Nanoparticle-Catalyzed Reductive Amination of Aldehydes with Nitroarenes Under Atmospheric Hydrogen.

A cobalt-rhodium heterobimetallic nanoparticle (Co2Rh2/C)-catalyzed tandem reductive amination of aldehydes with nitroaromatics to sec-amines has been developed. The tandem reaction proceeds without any additives under mild conditions (1 atm H2 and 25 °C). This procedure can be scaled up to the gram scale, and the catalyst can be reused more than six times without loss of activity.

Stability of Zr-Based UiO-66 Metal-Organic Frameworks in Basic Solutions.

Although Zr-based metal-organic frameworks (MOFs) exhibit robust chemical and physical stability in the presence of moisture and acidic conditions, their susceptibility to nucleophilic attacks from bases poses a critical challenge to their overall stability. Herein, we systematically investigate the stability of Zr-based UiO-66 (UiO = University of Oslo) MOFs in basic solutions. The impact of 11 standard bases, including inorganic salts and organic bases, on the stability of these MOFs is examined. The destruction of the framework is confirmed through powder X-ray diffraction (PXRD) patterns, and the monitored dissolution of ligands from the framework is assessed using nuclear magnetic resonance (NMR) spectroscopy. Our key findings reveal a direct correlation between the strength and concentration of the base and the destruction of the MOFs. The summarized data provide valuable insights that can guide the practical application of Zr-based UiO-66 MOFs under basic conditions, offering essential information for their optimal utilization in various settings.

The host protease KLK5 primes and activates spike proteins to promote human betacoronavirus replication and lung inflammation.

Coronaviruses rely on host proteases to activate the viral spike protein, which facilitates fusion with the host cell membrane and the release of viral genomic RNAs into the host cell cytoplasm. The distribution of specific host proteases in the host determines the host, tissue, and cellular tropism of these viruses. Here, we identified the kallikrein (KLK) family member KLK5 as a major host protease secreted by human airway cells and exploited by multiple human betacoronaviruses. KLK5 cleaved both the priming (S1/S2) and activation (S2') sites of spike proteins from various human betacoronaviruses in vitro. In contrast, KLK12 and KLK13 displayed preferences for either the S2' or S1/S2 site, respectively. Whereas KLK12 and KLK13 worked in concert to activate SARS-CoV-2 and MERS-CoV spike proteins, KLK5 by itself efficiently activated spike proteins from several human betacoronaviruses, including SARS-CoV-2. Infection of differentiated human bronchial epithelial cells (HBECs) with human betacoronaviruses induced an increase in KLK5 that promoted virus replication. Furthermore, ursolic acid and other related plant-derived triterpenoids that inhibit KLK5 effectively suppressed the replication of SARS-CoV, MERS-CoV, and SARS-CoV-2 in HBECs and mitigated lung inflammation in mice infected with MERS-CoV or SARS-CoV-2. We propose that KLK5 is a pancoronavirus host factor and a promising therapeutic target for current and future coronavirus-induced diseases.

Divergent C-H Amidations and Imidations by Tuning Electrochemical Reaction Potentials.

Electrochemical C-H functionalizations are attractive transformations, as they are capable of avoiding the use of transition metals, pre-oxidized precursors, or suprastoichiometric amounts of terminal oxidants. Herein an electrochemically tunable method was developed that enabled the divergent formation of cyclic amines or imines by applying different reaction potentials. Detailed cyclic voltammetry analyses, coupled with chronopotentiometry experiments, were carried out to provide insight into the mechanism, while atom economy was assessed through a paired electrolysis. Selective C-H amidations and imidations were achieved to afford five- to seven-membered sulfonamide motifs that could be employed for late-stage modifications.

Kinetics of neutralizing antibodies against SARS-CoV-2 infection according to sex, age, and disease severity.

Knowledge of the factors affecting the difference in kinetics and longevity of the neutralizing antibody (nAb) response to SARS-CoV-2 is necessary to properly prioritize vaccination. In the present study, from March to December 2020, of the 143 patients who recovered from COVID-19, 87 underwent study visits scheduled every 3 months. Patient demographics and blood samples were collected followed by a plaque reduction neutralization test to analyze nAb titers. A linear mixed model was used to compare the effects of sex, age, and disease severity over time. Results demonstrated a gradual reduction in nAb titers over time with a significant decrease from 6 to 9 months post-COVID-19 infection (p < 0.001). In time-to-sex, age, and disease severity comparisons, reduction in nAb titers over time was unaffected by sex (p = 0.167), age (p = 0.188), or disease severity (p = 0.081). Additionally, the nAb titer was 1.46 times significantly higher in those aged ≥ 50 years than in those aged < 50 years (p = 0.036) irrespective of time Moreover, the nAb titer was 2.41 times higher in the moderate or above than that in the below moderate disease severity group (p < 0.001). However, no significant differences were observed in terms of sex (p = 0.300). Given the reduction in nAbs over time, maintaining protective neutralizing antibodies regardless of sex, age, or disease severity is needed.

Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord.

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

Active and Recyclable Catalytic Synthesis of Indoles by Reductive Cyclization of 2-(2-Nitroaryl)acetonitriles in the Presence of Co-Rh Heterobimetallic Nanoparticles with Atmospheric Hydrogen under Mild Conditions.

A cobalt-rhodium heterobimetallic nanoparticle-catalyzed reductive cyclization of 2-(2-nitroaryl)acetonitriles to indoles has been achieved. The tandem reaction proceeds without any additives under the mild conditions (1 atm H2 and 25 °C). This procedure could be scaled up to the gram scale. The catalytic system is significantly stable under these reaction conditions and could be reused more than ten times without loss of catalytic activity.