Au(i)-mediated N2-elimination from triazaphospholes: a one-pot synthesis of novel N2P2-heterocycles

Novel tosyl- and mesitylsulfonyl-substituted triazaphospholes were synthesized and structurally characterized. In an attempt to prepare the corresponding Au(I)-complexes with stoichiometric amounts of AuCl·S(CH3)2, cyclo-1,3-diphospha(III)-2,4-diazane-AuCl-complexes were obtained instead. Our here presented results offer a new strategy for preparing such coordination compounds selectively in a one-pot approach

Catalytic oxygenation of sp3 “C-H” bonds with Ir(III) complexes of chelating triazoles and mesoionic carbenes

Cp*-Ir(III) complexes with additional chelating ligands are known active pre- catalysts for the oxygenation of C–H bonds. We present here eight examples of such complexes where the denticity of the chelating ligands has been varied from the well-known 2,2′-bpy through pyridyl-triazole, bi-triazole to ligands containing pyridyl-triazolylidene, triazolyl-triazolylidene and bi- triazolylidenes. Additionally, we also compare the catalytic results to complexes containing chelating cyclometallated ligands with additional triazole or triazolylidene donors. Single crystal X-ray structural data are presented for all the new complexes that contain one or more triazolylidene donors of the mesoionic carbene type. We present the first example of a metal complex containing a chelating triazole-triazolylidene ligand. The results of the catalytic screening show that complexes containing unsymmetrical donors of the pyridyl-triazole or pyridyl-triazolylidene types are the most potent pre- catalysts for the C–H oxygenation of cyclooctane in the presence of either m-CPBA or NaIO4 as a sacrificial oxidant. These pre-catalysts can also be used to oxygenate C–H bonds in other substrates such as fluorene and ethyl benzene. The most potent pre-catalysts presented here work with a lower catalyst loading and under milder conditions while delivering better product yields in comparison with related literature known Ir(III) pre-catalysts. These results thus point to the potential of ligands with unsymmetrical donors obtained through the click reaction in oxidation catalysis

Highly Crystalline and Semiconducting Imine-Based Two-Dimensional Polymers Enabled by Interfacial Synthesis

Single-layer and multi-layer 2D polyimine films have been achieved through interfacial synthesis methods. However, it remains a great challenge to achieve the maximum degree of crystallinity in the 2D polyimines, which largely limits the long-range transport properties. Here we employ a surfactant-monolayer-assisted interfacial synthesis (SMAIS) method for the successful preparation of porphyrin and triazine containing polyimine-based 2D polymer (PI-2DP) films with square and hexagonal lattices, respectively. The synthetic PI-2DP films are featured with polycrystalline multilayers with tunable thickness from 6 to 200 nm and large crystalline domains (100–150 nm in size). Intrigued by high crystallinity and the presence of electroactive porphyrin moieties, the optoelectronic properties of PI-2DP are investigated by time-resolved terahertz spectroscopy. Typically, the porphyrin-based PI-2DP 1 film exhibits a p-type semiconductor behavior with a band gap of 1.38 eV and hole mobility as high as 0.01 cm2 V−1 s−1, superior to the previously reported polyimine based materials. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Nanoparticle proximity controls selectivity in benzaldehyde hydrogenation

Disentangling the effects of nanoparticle proximity and size on thermal catalytic performance is challenging with traditional synthetic methods. Here we adapt a modular raspberry-colloid-templating approach to tune the average interparticle distance of PdAu alloy nanoparticles, while preserving all other physicochemical characteristics, including nanoparticle size. By controlling the metal loading and placement of pre-formed nanoparticles within a 3D macroporous SiO2 support and using the hydrogenation of benzaldehyde to benzyl alcohol and toluene as the probe reaction, we report that increasing the interparticle distance (from 12 to 21 nm) substantially enhances selectivity towards benzyl alcohol (from 54% to 99%) without compromising catalytic performance. Combining electron tomography, kinetic evaluation and simulations, we show that interparticle distance modulates the local benzyl alcohol concentration profile between active sites, consequently affecting benzyl alcohol readsorption, which promotes hydrogenolysis to toluene. Our results illustrate the relevance of proximity effects as a mesoscale tool to control the adsorption of intermediates and, hence, catalytic performance. (Figure presented.)

Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3

Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers

Identifying the Optimal Pd Ensemble Size in Dilute PdAu Alloy Nanomaterials for Benzaldehyde Hydrogenation

Unraveling metal nuclearity effects is central for active site identification and the development of high-performance heterogeneous catalysts. Herein, a platform of nanostructured palladium (Pd) in gold (Au) dilute alloy nanoparticles supported on raspberry-colloid-templated (RCT) silica was employed to systematically assess the impact of the Pd ensemble size for the low-nuclearity regime in the Au surface layer, from single atoms to clusters, on the catalytic performance in the liquid-phase hydrogenation of benzaldehyde to benzyl alcohol. Combining catalyst evaluation, detailed characterization, and mechanistic studies based on density functional theory, we show that Pd single atoms in the Au surface plane (corresponding to samples with 4 atom % Pd in Au) are virtually inactive in this reaction and benzyl alcohol production is optimal over small Pd clusters (corresponding to samples with 10-12 atom % Pd in Au) due to superior benzaldehyde adsorption and transition state stabilization for the C-H bond formation step. For larger Pd ensembles (samples with ≥10 atom % Pd in Au), C-O bond hydrogenolysis occurs, promoting toluene formation and decreasing the selectivity toward benzyl alcohol, in line with a relatively lowered C-O bond cleavage barrier. Nevertheless, the nanostructured bimetallic Pd13Au87/SiO2-RCT catalyst still outperforms monometallic Pd counterparts in terms of selectivity for benzyl alcohol over toluene at comparable conversion and rate. Furthermore, the stability is improved compared to pure Pd nanoparticles due to inhibited particle agglomeration in the RCT silica matrix

Nanostructured Catalysts for Sustainable Acetylene-Based Vinyl Chloride Production

The growing demand for plastics coupled with shrinking oil reserves has revived interest in the production of vinyl chloride (VCM), monomer to polyvinyl chloride, from coal-derived acetylene. However, the present acetylene hydrochlorination process relies on toxic mercuric chloride-based catalysts, the use of which will be banned from 2022, highlighting the urgency to implement sustainable and economically viable alternatives. Since decades, the search for a suitable replacement has been guided by the linear correlation between activity and the standard electrode potential of metal chlorides, directing research efforts primary towards carbon-supported gold catalysts. Still, several practical challenges and fundamental questions remain unsolved. While Au single atoms exhibit high initial activity, they rapidly agglomerate into inactive particles due to their insufficient stability on carbon. Furthermore, the established performance descriptor cannot provide reliable guidelines for the design of superior catalytic architectures, as speciation effects and stability of the metal nanostructures are not considered. Finally, the key role of carbon in generating active metal-based catalysts compared to any other support is still not understood. In fact, a complex interplay exists between the metal site and the carbon support, exhibiting as such notable activity in acetylene hydrochlorination, particularly upon functionalization with heteroatoms. This thesis disentangles the interplay between the metal nanostructure and the carbon support in acetylene hydrochlorination and unravels fundamental understanding on the active sites through speciation-performance analyses, providing guidelines for the optimal design of metal-free and nanostructured metal-based catalysts. To reach this goal, a holistic approach, combining precise material synthesis, in-depth characterization, quantitative catalytic evaluation, kinetic and transient mechanistic analyses, and density functional theory studies is adopted. Firstly, the potential of nitrogen-doped carbons (NC) as metal-free hydrochlorination catalysts is explored. By decoupling structural, compositional, and porous properties, an interplay of two activity descriptors is identified: (i) a high content of pyrrolic-N functionalities, being responsible for the adsorption of the reactants, and (ii) good electrical conductivity,x likely influencing the surface diffusion of adsorbed species. With this understanding, the first metal-free catalyst is developed that rivals the initial activity of gold-based systems at elevated reaction temperatures (473 K and 573 K, for metal-based and metal-free catalysts, respectively). However, the active sites promote extensive coking, leading to micropore blockage and rapid catalyst deactivation (deactivation constant kD = -20 h−1). The introduction of structurally more stable meso- and macropores results into a ca. 50-fold reduced deactivation rate of hierarchical NC at half the initial activity level compared to their purely microporous counterparts. Building on the acquired knowledge to functionalize carbons, host design strategies are developed to control the nuclearity and coordination environment of gold, platinum, palladium, ruthenium, rhodium, and iridium-based catalysts. Following this approach, metal speciation and host effects can be disentangled, enabling the derivation of generalized quantitative performance descriptors for acetylene hydrochlorination. Distinct active-site nanostructures were identified: (i) MClx single atoms of Au and Pt, (ii) metal oxide nanoparticles of Ru, Rh, and Ir and, (iii) metallic nanoparticles of Pd. The energy of acetylene adsorption is identified as speciation sensitive activity descriptor. Further, also the selectivity with respect to the formation of coke is mainly determined by the acetylene-affinity of the metals (i.e., maximized over Pd nanoparticles) and the functionalization of the carbon support (i.e., maximized over NC). Besides coking, chlorination and metal nuclearity changes are relevant deactivation mechanisms, originating from an interplay of two stability descriptors: (i) the single atom-carbon host interaction and (ii) the affinity towards chlorine. Specifically, all nanostructures of Au and Pd suffer from agglomeration on N-free carbon, while being sufficiently stabilized on NC. Oxidic nanoparticles of Ru, Rh, and Ir undergo chlorination and redispersion into fully chlorinated inactive single atoms, regardless of the host functionalization. In the case of Ru/NC, this process can be inhibited through encapsulation into single-layer graphene shells. In combination with optimized oxygen co-feeding to reduce coking while preserving the protective layer, the nanostructured Ru catalyst can achieve comparable activity and stability to Au single-atoms on NC (kD = -1.3 h−1). On non-functionalized carbon, Pt single atoms are identified as the only metal nanostructure with intrinsic stability on O/C defects. This endows them with unparalleled durability in acetylene hydrochlorination (kD = -0.1 h−1), ultimately surpassing the space-time-xi yield of state-of-the-art Au- and Ru-based catalysts and qualifying them as a new promising candidate for sustainable vinyl chloride production. The discovery of stable carbon-supported Pt single atoms further allowed to systematically vary the porous properties and surface functionalization of carbon while preserving the metal speciation, shedding light on the intrinsic role of the support. A high acetylene adsorption capacity in HCl-rich atmosphere is identified as the central activity descriptor, which is finely controllable through the porosity of the carbon host. The rate of coking as the main deactivation mechanism is decreased by reducing the density of acidic surface groups. With the aim to combine the high initial activity of Au single atoms with the unprecedented stability of their Pt-based analogs, synergies in bimetallic catalysts are explored. Thereby, we reveal the potential of Pt chloride in aqueous solution to disperse large gold agglomerates (>70 nm) on carbon carriers into single atoms, a phenomenon of practical relevance beyond the field of acetylene hydrochlorination. Furthermore, the formed bimetallic single-atom catalyst exhibits improved resistance against agglomeration, indicating cooperativity effects between gold and platinum atoms and giving exciting future prospects for multimetallic single-atom catalysis. This thesis demonstrates how catalysis can be enhanced via precise nanoscale engineering, giving momentum to future developments in acetylene hydrochlorination and single-atom catalysis

Descriptors for High-Performance Nitrogen-Doped Carbon Catalysts in Acetylene Hydrochlorination

ISSN:2155-543

Watching object related movements modulates mirror-like activity in parietal brain regions

Objective: We studied the activation of cortical motor and parietal areas during the observation of object related grasping movements. By manipulating the type of an object (realistic versus abstract) and the type of grasping (correct versus incorrect), we addressed the question how observing such object related movements influences cortical rhythmicity, especially the mu-rhythm, in the context of an ‘‘extended’’ human mirror neuron system (MNS). Methods: Multichannel electroencephalogram (EEG) was recorded during the observation of different object-related grasping actions in twenty healthy subjects. Different movies were presented, showing sequences of correct or incorrect hand grasping actions related to an abstract or realistic (daily life) object. Results: Event-related de/synchronization (ERD/ERS) analyses revealed a larger ERD in the upper alpha (10–12 Hz), beta (16–20 Hz) and gamma (36–40 Hz) frequency bands over parietal brain regions depending on the type of grasping. The type of object only influenced ERD patterns in the gamma band range (36–40 Hz) at parietal sites suggesting a strong relation of gamma band activity and cortical object representation. Abstract and realistic objects produced lower beta band synchronization at central sites only, whereas depending on the type of grasping an ERS in the upper alpha band (10–12 Hz) was observed. Conclusion: Depending on the type of the grasped object and the type of grasping stronger parietal cortical activation occurred during movement observation. Significance: Discussing the results in terms of an ‘‘extended’’ human mirror neuron system (MNS), it could be concluded that beside sensorimotor areas a stronger involvement of parietal brain regions was found depending on the type of object and grasping movement observed