Importance of Metal-Support Interactions for CO2 Hydrogenation: An Operando Near-Ambient Pressure X-ray Photoelectron Spectroscopy Study on Gold-Loaded In2O3 and CeO2 Catalysts.

Metal-support interactions, which are essential for the design of supported metal catalysts, used, e.g., for CO2 activation, are still only partially understood. In this study of gold-loaded In2O3 and CeO2 catalysts during CO2 hydrogenation using near-ambient pressure X-ray photoelectron spectroscopy, supported by near edge X-ray absorption fine structure, we demonstrate that the role of the noble metal strongly depends upon the choice of the support material. Temperature-dependent analyses of X-ray photoelectron spectra under reaction conditions reveal that gold is reduced on CeO2, enabling direct H2 activation, but oxidized on In2O3, leading to decreased activity of Au/In2O3 compared to bare In2O3. At elevated temperatures, the catalytic activity of the In2O3 catalysts strongly increases as a result of facilitated CO2 and (In2O3-based) H2 activation, while the catalytic activity of Au/CeO2 is limited by reoxidation by CO2. Our results underline the importance of operando studies for understanding metal-support interactions to enable a rational support selection in the future.

Refining the mechanism of CO2 and H2 activation over gold-ceria catalysts by IR modulation excitation spectroscopy.

The activation and utilization of the greenhouse gas CO2 is of great interest for the energy transition as a fossil-free carbon source for mitigating climate change. CO2 hydrogenation via the reverse water-gas shift reaction (RWGSR) converts CO2 to CO, a crucial component of syngas, enabling further transformation by means of the Fischer-Tropsch process. In this study, we unravel the detailed mechanism of the RWGSR on low-loaded Au/CeO2 catalysts using IR modulation excitation spectroscopy (MES), by periodically modulating the concentration of the reactants, followed by phase-sensitive detection (PSD). Applying such a MES-PSD approach to Au/CeO2 catalysts during RWGSR gives direct spectroscopic evidence for the active role of gold hydride, bidentate carbonate and hydroxyl species in the reaction mechanism, while disproving the participation of other species such as formate. Our results highlight the potential of modulation excitation spectroscopy combined with phase-sensitive detection to provide new mechanistic insight into catalytic reactions not accessible by steady-state techniques, including a profound understanding of the sequence of reaction steps.

A Bispecific, Tetravalent Antibody Targeting Inflammatory and Pruritogenic Pathways in Atopic Dermatitis.

Inhibition of IL-4/IL-13 signaling has dramatically improved the treatment of atopic dermatitis (AD). However, in many patients, clinical responses are slow to develop and remain modest. Indeed, some symptoms of AD are dependent on IL-31, which is only partially reduced by IL-4/IL-13 inhibition. Thus, there is an unmet need for AD treatments that concomitantly block IL-4/IL-13 and IL-31 pathways. We engineered NM26-2198, a bispecific tetravalent antibody designed to accomplish this task. In reporter cell lines, NM26-2198 concomitantly inhibited IL-4/IL-13 and IL-31 signaling with a potency comparable with that of the combination of an anti-IL-4Rα antibody (dupilumab) and an anti-IL-31 antibody (BMS-981164). In human PBMCs, NM26-2198 inhibited IL-4-induced upregulation of CD23, demonstrating functional binding to FcγRII (CD32). NM26-2198 also inhibited the secretion of the AD biomarker thymus and activation-regulated chemokine (TARC) in blood samples from healthy human donors. In male cynomolgus monkeys, NM26-2198 exhibited favorable pharmacokinetics and significantly inhibited IL-31-induced scratching at a dose of 30 mg/kg. In a repeat-dose, good laboratory practice toxicology study in cynomolgus monkeys, no adverse effects of NM26-2198 were observed at a weekly dose of 125 mg/kg. Together, these results justify the clinical investigation of NM26-2198 as a treatment for moderate-to-severe AD.

Unraveling surface and bulk dynamics of iron(III) molybdate during oxidative dehydrogenation using operando and transient spectroscopies.

Iron(III) molybdate (Fe2(MoO4)3) is a commercial catalyst for the oxidative dehydrogenation (ODH) of methanol, but it has recently been shown to be relevant for other substrates as well. Despite its commercial use, a detailed mechanistic understanding of Fe2(MoO4)3 catalysts at the surface and in the bulk has been lacking, largely hampered by the lack of suitable spectroscopic methods, directly applicable under reaction conditions. Using propane ODH as an example, we highlight the potential of operando Raman and impedance spectroscopy combined with transient IR spectroscopy, to identify surface active sites and monitor the hydrogen transfer and oxygen dynamics. By comparison with the behavior of reference compounds (MoO3, MoOx/Fe2O3) a mechanistic model is proposed. The presence of iron greatly influences the reactivity behavior via oxygen diffusion but is moderated in its oxidative capacity by surface MoOx. Our approach directly elucidates fundamental properties of Fe2(MoO4)3 of general importance to selective oxidation catalysis.

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin.

Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

Design of antibody variable fragments with reduced reactivity to preexisting anti-drug antibodies.

Upon reformatting of an antibody to single-chain variable fragment format, a region in the former variable/constant domain interface of the heavy chain becomes accessible for preexisting (PE) anti-drug antibody (ADA) binding. The region exposed because of this reformatting contains a previously hidden hydrophobic patch. In this study, mutations are introduced in this region to reduce PE ADA reactivity and concomitantly reduce the hydrophobic patch. To enhance our understanding of the importance of individual residues in this region with respect to PE ADA reactivity, a total of 50 molecules for each of two antibodies against different tumor-associated antigens were designed, produced, and characterized by an arsenal of biophysical methods. The aim was to identify suitable mutations that reduce, or completely eliminate, PE ADA reactivity to variable fragments, without compromising biophysical and pharmacodynamic properties. Computational methods were used to pinpoint key residues to mutate and to evaluate designed molecules in silico, in order to reduce the number of molecules to produce and characterize experimentally. Mutation of two threonine residues, Thr101 and Thr146 in the variable heavy domain, proved to be critical to eliminate PE ADA reactivity. This may have important implications in optimizing early drug development for antibody fragment-based therapeutics.

MXene Aerogel Derived Ultra-Active Vanadia Catalyst for Selective Conversion of Sustainable Alcohols to Base Chemicals.

Selective oxidation reactions are an important class of the current chemical industry and will be highly important for future sustainable chemical production. Especially, the selective oxidation of primary alcohols is expected to be of high future interest, as alcohols can be obtained on technical scales from biomass fermentation. The oxidation of primary alcohols produces aldehydes, which are important intermediates. While selective methanol oxidation is industrially established, the commercial catalyst suffers from deactivation. Ethanol selective oxidation is not commercialized but would give access to sustainable acetaldehyde production when using renewable ethanol. In this work, it is shown that employing 2D MXenes as building blocks allows one to design a nanostructured oxide catalyst composed of mixed valence vanadium oxides, which outperforms on both reactions known materials by nearly an order of magnitude in activity, while showing high selectivity and stability. The study shows that the synthesis route employing 2D materials is key to obtain these attractive catalysts. V4C3Tx MXene structured as an aerogel precursor needs to be employed and mildly oxidized in an alcohol and oxygen atmosphere to result in the aspired nanostructured catalyst composed of mixed valence VO2, V6O13, and V3O7. Very likely, the bulk stable reduced valence state of the material together coupled with the nanorod arrangement allows for unprecedented oxygen mobility as well as active sites and results in an ultra-active catalyst.

Berezinskii-Kosterlitz-Thouless Transition in the Type-I Weyl Semimetal PtBi2.

Symmetry breaking in topological matter has become in recent years a key concept in condensed matter physics to unveil novel electronic states. In this work, we predict that broken inversion symmetry and strong spin-orbit coupling in trigonal PtBi2 lead to a type-I Weyl semimetal band structure. Transport measurements show an unusually robust low dimensional superconductivity in thin exfoliated flakes up to 126 nm in thickness (with Tc ∼ 275-400 mK), which constitutes the first report and study of unambiguous superconductivity in a type-I Weyl semimetal. Remarkably, a Berezinskii-Kosterlitz-Thouless transition with TBKT ∼ 310 mK is revealed in up to 60 nm thick flakes, which is nearly an order of magnitude thicker than the rare examples of two-dimensional superconductors exhibiting such a transition. This makes PtBi2 an ideal platform to study low dimensional and unconventional superconductivity in topological semimetals.

Spinon Heat Transport in the Three-Dimensional Quantum Magnet PbCuTe_{2}O_{6}.

Quantum spin liquids (QSLs) are novel phases of matter which remain quantum disordered even at the lowest temperature. They are characterized by emergent gauge fields and fractionalized quasiparticles. Here we show that the sub-kelvin thermal transport of the three-dimensional S=1/2 hyperhyperkagome quantum magnet PbCuTe_{2}O_{6} is governed by a sizeable charge-neutral fermionic contribution which is compatible with the itinerant fractionalized excitations of a spinon Fermi surface. We demonstrate that this hallmark feature of the QSL state is remarkably robust against sample crystallinity, large magnetic field, and field-induced magnetic order, ruling out the imitation of QSL features by extrinsic effects. Our findings thus reveal the characteristic low-energy features of PbCuTe_{2}O_{6} which qualify this compound as a true QSL material.

Operando spectroelectrochemistry of bulk-exfoliated 2D SnS2 for anodes within alkali metal ion batteries reveals unusual tin (III) states.

In this study we report an affordable synthesis and preparation of an electrochemically exfoliated few-layer 2-dimensional (2D) SnS2 anode material of high cycling durability and demonstrate its performance on the example of alkali metal batteries. The metalation mechanism consists of highly unusual and previously only speculated Sn (III)-state grasped by operando Raman spectroelectrochemistry aided by symmetry analysis. The prepared 2D material flakes were characterized by high resolution transmission electron microscopy, X-ray photoelectron and Raman spectroscopies. The operando Raman spectroelectrochemistry was chosen as a dedicated tool for the investigation of alkali-metal-ion intercalation (Li, Na, K), whereby the distortion of the A1g Raman active mode (out-of-plane S-Sn-S vibration) during battery charging exhibited a substantial dependence on the electrochemically applied potential. As a result of the structural dynamics a considerable Raman red-shift of 17.6 cm-1 was observed during metalation. Linewidth changes were used to evaluate the expansion caused by metalation, which in case of sodium and potassium were found to be minimal compared to lithium. Based on the spectroscopic and electrochemical results, a mechanism for the de-/intercalation of lithium, sodium and potassium is proposed which includes alloying in few-layer 2D SnS2 materials and the generation of point-defects.

Rational Design of Mesoporous CuO-CeO2 Catalysts for NH3-SCR Applications Guided by Multiple In Situ Spectroscopies.

Efficient nontoxic catalysts for low-temperature NH3 selective catalytic reduction (NH3-SCR) applications are of great interest. Owing to their promising redox and low-temperature activity, we prepared CuO-CeO2 catalysts on a mesoporous SBA-15 support using targeted solid-state impregnation (SSI), guided by multiple in situ spectroscopy. The use of template P123 allowed dedicated modification of the surface properties of the SBA-15 matrix, resulting in a changed reactivity behavior of the metal precursors during the calcination process. To unravel the details of the transformation of the precursors to the final catalyst material, we applied in situ diffuse reflectance infrared Fourier transform (DRIFT), UV-visible (UV-vis), and Raman spectroscopies as well as online Fourier transform infrared (FTIR) monitoring of the gas-phase composition, in addition to ex situ surface, porosity, and structural analysis. The in situ analysis reveals two types of nitrate decomposition mechanisms: a nitrate-bridging route leading to the formation of a CuO-CeO2 solid solution with increased low-temperature NH3-SCR activity, and a hydrolysis route, which facilitates the formation of binary oxides CuO + CeO2 showing activity over a broader temperature window peaking at higher temperatures. Our findings demonstrate that a detailed understanding of catalytic performance requires a profound knowledge of the calcination step and that the use of in situ analysis facilitates the rational design of catalytic properties.

Unraveling the Active Vanadium Sites and Adsorbate Dynamics in VOx/CeO2 Oxidation Catalysts Using Transient IR Spectroscopy.

The oxidative dehydrogenation (ODH) of propane over supported vanadia catalysts is an attractive route toward propene (propylene) with the potential of industrial application and has been extensively studied over decades. Despite numerous mechanistic studies, the active vanadyl site of the reaction has not been elucidated. In this work, we unravel the ODH reaction mechanism, including the nuclearity-dependent vanadyl and surface dynamics, over ceria-supported vanadia (VOx/CeO2) catalysts by applying (isotopic) modulation excitation IR spectroscopy supported by operando Raman and UV-vis spectroscopies. Based on our loading-dependent analysis, we were able to identify two different mechanisms leading to propylene, which are characterized by isopropyl- and acrylate-like intermediates. The modulation excitation IR approach also allows for the determination of the time evolution of the vanadia, hydroxyl, and adsorbate dynamics, underlining the intimate interplay between the surface vanadia species and the ceria support. Our results highlight the potential of transient IR spectroscopy to provide a detailed understanding of reaction mechanisms in oxidation catalysis and the dynamics of surface catalytic processes in general.

Elucidating CO2 Hydrogenation over In2 O3 Nanoparticles using Operando UV/Vis and Impedance Spectroscopies.

In2 O3 has emerged as a promising catalyst for CO2 activation, but a fundamental understanding of its mode of operation in CO2 hydrogenation is still missing, as the application of operando vibrational spectroscopy is challenging due to absorption effects. In this mechanistic study, we systematically address the redox processes related to the reverse water-gas shift reaction (rWGSR) over In2 O3 nanoparticles, both at the surface and in the bulk. Based on temperature-dependent operando UV/Vis spectra and a novel operando impedance approach for thermal powder catalysts, we propose oxidation by CO2 as the rate-determining step for the rWGSR. The results are consistent with redox processes, whereby hydrogen-containing surface species are shown to exhibit a promoting effect. Our findings demonstrate that oxygen/hydrogen dynamics, in addition to surface processes, are important for the activity, which is expected to be of relevance not only for In2 O3 but also for other reducible oxide catalysts.

The diagnostic value of sleep and vigilance tests in central disorders of hypersomnolence.

STUDY OBJECTIVES: This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes. METHODS: Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997-2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference. RESULTS: An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome. CONCLUSION: This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.

Operando Raman Shift Replaces Current in Electrochemical Analysis of Li-ion Batteries: A Comparative Study.

Li-rich and catalytically active γ-LixV2O5 (x = 1.48) was investigated as a cathode for its heterogeneous charge transfer kinetics. Using a specially designed two-electrode system lithium half cell, Butler-Volmer analysis was performed, and Raman spectra were acquired in 18 mV intervals. A direct correlation was observed between the Raman shift of the active modes Ag,Bg, Au, and Bu, and the development of the Faraday current at the working electrode. The Raman intensity and the Raman shift were implemented to replace the current in a Tafel plot used for the analysis of Butler-Volmer kinetics. Striking similarities in the charge transfer proportionality constants α were found for current and Raman-based analysis. The potential of this new method of Raman-aided electrochemical detection at the diffraction limit is discussed.

Conical Nanotubes Synthesized by Atomic Layer Deposition of Al2O3, TiO2, and SiO2 in Etched Ion-Track Nanochannels.

Etched ion-track polycarbonate membranes with conical nanochannels of aspect ratios of ~3000 are coated with Al2O3, TiO2, and SiO2 thin films of thicknesses between 10 and 20 nm by atomic layer deposition (ALD). By combining ion-track technology and ALD, the fabrication of two kinds of functional structures with customized surfaces is presented: (i) arrays of free-standing conical nanotubes with controlled geometry and wall thickness, interesting for, e.g., drug delivery and surface wettability regulation, and (ii) single nanochannel membranes with inorganic surfaces and adjustable isoelectric points for nanofluidic applications.

Toward an Atomic-Level Understanding of Ceria-Based Catalysts: When Experiment and Theory Go Hand in Hand.

ConspectusBecause ceria (CeO2) is a key ingredient in the formulation of many catalysts, its catalytic roles have received a great amount of attention from experiment and theory. Its primary function is to enhance the oxidation activity of catalysts, which is largely governed by the low activation barrier for creating lattice O vacancies. Such an important characteristic of ceria has been exploited in CO oxidation, methane partial oxidation, volatile organic compound oxidation, and the water-gas shift (WGS) reaction and in the context of automotive applications. A great challenge of such heterogeneously catalyzed processes remains the unambiguous identification of active sites.In oxidation reactions, closing the catalytic cycle requires ceria reoxidation by gas-phase oxygen, which includes oxygen adsorption and activation. While the general mechanistic framework of such processes is accepted, only very recently has an atomic-level understanding of oxygen activation on ceria powders been achieved by combined experimental and theoretical studies using in situ multiwavelength Raman spectroscopy and DFT.Recent studies have revealed that the adsorption and activation of gas-phase oxygen on ceria is strongly facet-dependent and involves different superoxide/peroxide species, which can now be unambiguously assigned to ceria surface sites using the combined Raman and DFT approach. Our results demonstrate that, as a result of oxygen dissociation, vacant ceria lattice sites are healed, highlighting the close relationship of surface processes with lattice oxygen dynamics, which is also of technical relevance in the context of oxygen storage-release applications.A recent DFT interpretation of Raman spectra of polycrystalline ceria enables us to take account of all (sub)surface and bulk vibrational features observed in the experimental spectra and has revealed new findings of great relevance for a mechanistic understanding of ceria-based catalysts. These include the identification of surface oxygen (Ce-O) modes and the quantification of subsurface oxygen defects. Combining these theoretical insights with operando Raman experiments now allows the (sub)surface oxygen dynamics of ceria and noble metal/ceria catalysts to be monitored under the reaction conditions.Applying these findings to Au/ceria catalysts provides univocal evidence for ceria support participation in heterogeneous catalysis. For room-temperature CO oxidation, operando Raman monitoring the (sub)surface defect dynamics clearly demonstrates the dependence of catalytic activity on the ceria reduction state. Extending the combined experimental/DFT approach to operando IR spectroscopy allows the elucidation of the nature of the active gold as (pseudo)single Au+ sites and enables us to develop a detailed mechanistic picture of the catalytic cycle. Temperature-dependent studies highlight the importance of facet-dependent defect formation energies and adsorbate stabilities (e.g., carbonates). While the latter aspects are also evidenced to play a role in the WGS reaction, the facet-dependent catalytic performance shows a correlation with the extent of gold agglomeration. Our findings are fully consistent with a redox mechanism, thus adding a new perspective to the ongoing discussion of the WGS reaction.As outlined above for ceria-based catalysts, closely combining state-of-the-art in situ/operando spectroscopy and theory constitutes a powerful approach to rational catalyst design by providing essential mechanistic information based on an atomic-level understanding of reactions.

Borate-driven ionic rectifiers based on sugar-bearing single nanochannels.

Recently, much scientific effort has been centered on the control of the ionic transport properties of solid state nanochannels and the rational design and integration of chemical systems to induce changes in the ionic transport by means of interactions with selected target molecules. Here, we report the fabrication of a novel nanofluidic device based on solid-state nanochannels, which combines silane chemistry with both track-etched and atomic layer deposition (ALD) technologies. Nanodevice construction involves the coating of bullet-shaped single-pore nanochannels with silica (SiO2) by ALD and subsequent surface modification by reaction between silanol groups exposed on pore walls and N-(3-triethoxysilylpropyl)-gluconamide, in order to create a gluconamide-decorated nanochannel surface. The formation of a boroester derivative resulting from the selective reaction of borate with the appended saccharides leads to important changes in the surface charge density and, concomitantly, in the iontronic properties of the nanochannel. Furthermore, we propose a binding model to rationalize the specific interaction saccharide-borate in the surface. Besides, this unique nanodevice exhibits a highly selective and reversible response towards borate/fructose exposure. On the basis of the surface charge variation resulting from borate binding, the nanochannel can reversibly switch between "ON" and "OFF" states in the presence of borate and fructose, respectively. In addition, this work describes the first report of the functionalization of PET/SiO2 nanochannels by the ALD technique. We believe that this work provides a promising framework for the development of new nanochannel-based platforms suitable for multiple applications, such as water quality monitoring or directed molecular transport and separation.