Slow Deactivation Research Articles

Using Support Effects to Increase the Productivity of Immobilized Ruthenium Hydride Catalysts for the Hydrogenation of CO2.

Interfaces between catalytically active metal surfaces/sites and metal oxides (such as those formed by metal oxides covering metal nanoparticles by strong metal-support interactions) allow both the metal and metal oxide to react with substrates simultaneously and are important for the activity of many heterogeneously catalyzed reactions. However, similar interactions for well-defined immobilized catalysts have not been investigated, despite their potential for increasing catalytic activity. We test the reactivity of a ruthenium hydride [H2Ru(PPh3)2(Ph2P)2NC3H6Si(OEt)3 (1)] in the amine-promoted hydrogenation of CO2 as both a homogeneous catalyst and anchored on SiO2, Al2O3, ZnO, and SBA-15. Anchoring 1 on the surfaces resulted in varying degrees of surface collapse (formation of H-Ru-O linkages to the surface), with ZnO and confinement in SBA-15 pores giving the least surface collapse. Immobilization of 1 on ZnO gave a 6-fold improvement of the catalytic rate over the corresponding homogeneous catalyst. This increase in the catalytic productivity was only possible when the complex was in close contact with ZnO and is most likely due to a combination of increased catalytic activity and slower deactivation. These results demonstrate the ability of surface effects to vastly improve the productivity of even mediocre catalysts upon surface immobilization.

Role of Interfacial Hydrogen in Ethylene Hydrogenation on Graphite-Supported Ag, Au, and Cu Catalysts.

A combined surface science/microreactor approach was applied to examine interface effects in ethylene hydrogenation on carbon-supported Ag, Au, and Cu nanoparticle catalysts. Turnover frequencies (TOFs) were substantially higher for supported catalysts than for (unsupported) polycrystalline metal foils, especially for Ag. Spark ablation of the corresponding metals on highly oriented pyrolytic graphite (HOPG) and carbon-coated grids yielded nanoparticles of around 3 nm size that were well-suited for characterization by X-ray photoelectron spectroscopy (XPS), high-resolution (scanning) transmission electron microscopy (HRTEM/STEM), and energy dispersive X-ray spectroscopy (EDX). Polycrystalline metal foils characterized by scanning electron microscopy (SEM), EDX, electron backscatter diffraction (EBSD), XPS, and low-energy ion scattering (LEIS) served as unsupported references. Employing a UHV-compatible flow microreactor and gas chromatography (GC) allowed us to determine the catalytic performance of the model catalysts in ethylene hydrogenation up to 200 °C under atmospheric pressure. Compared to the pure metal foils, the HOPG-supported metal nanoparticles exhibited not only strongly increased activity but also higher stability (slower deactivation) and differing reaction orders. For the most active Ag catalysts, DFT calculations were carried out to determine the adsorption energies of the reacting species on single-crystal surfaces as well as on carbon-supported and unsupported Ag nanoparticles. Adsorption of molecular hydrogen was very weak on all unsupported Ag surfaces, resulting in hydrocarbon-"poisoned" surfaces. However, when a carbon support was present, the adsorption strength of H2 on Ag nanoparticles increased on average by -0.5 eV, driven by changes in Ag-Ag distances near the metal-carbon three-phase boundary (whereas subsurface carbon lowers hydrogen bonding). On Cu particles, the interface effect was calculated to be somewhat weaker than for Ag particles. H2/D2 scrambling experiments on Ag catalysts then corroborated a facilitated hydrogen activation for carbon-supported metals. Thus, the carbon support effect is attributed to an improved hydrogen availability at the metal-carbon interface, controlling performance.

Persistent (Nav1.9) sodium currents in human dorsal root ganglion neurons.

Nav1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Nav1.9, SCN11a, that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Nav1.9 has been learned through the study of rodent sensory neurons, and there is only 76% identity between human and rodent homologs of SCN11a, there is reason to suggest that there may be differences in the biophysical properties of the channels in human and rodent sensory neurons, and consequently, the contribution of these channels to the control of sensory neuron excitability, if not pain. Thus, the purpose of this study was to characterize Nav1.9 currents in human sensory neurons and compare the properties of these currents with those in rat sensory neurons recorded under identical conditions. Whole-cell patch clamp techniques were used to record Nav1.9 currents in isolated sensory neurons in vitro. Our results indicate that several of the core biophysical properties of the currents, including persistence and a low threshold for activation, are conserved across species. However, we noted a number of potentially important differences between the currents in human and rat sensory neurons including a lower threshold for activation, higher threshold for inactivation, slower deactivation, and faster recovery from slow inactivation. Human Nav1.9 was inhibited by inflammatory mediators, whereas rat Nav1.9 was potentiated. Our results may have implications for the role of Nav1.9 in sensory, if not nociceptive signaling.

Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations

A major driver of neuronal hyperexcitability is dysfunction of K+ channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders. However, the impact of these variants on the molecular mechanisms underlying KCNQ3 channel function remains poorly understood and existing treatments have significant side effects. Here, we use voltage clamp fluorometry, molecular dynamic simulations, and electrophysiology to investigate NDD-associated variants in KCNQ3 channels. We identified two distinctive mechanisms by which loss– and gain–of function NDD-associated mutations in KCNQ3 affect channel gating: one directly affects S4 movement while the other changes S4-to-pore coupling. MD simulations and electrophysiology revealed that polyunsaturated fatty acids (PUFAs) primarily target the voltage-sensing domain in its activated conformation and form a weaker interaction with the channel’s pore. Consistently, two such compounds yielded partial and complete functional restoration in R227Q- and R236C-containing channels, respectively. Our results reveal the potential of PUFAs to be developed into therapies for diverse KCNQ3-based channelopathies.

Direct conversion of methane to aromatics and hydrogen via a heterogeneous trimetallic synergistic catalyst

Non-oxidative methane dehydro-aromatization reaction can co-produce hydrogen and benzene effectively on a molybdenum-zeolite based thermochemical catalyst, which is a very promising approach for natural-gas upgrading. However, the low methane conversion and aromatics selectivity and weak durability restrain the realistic application for industry. Here, a mechanism for enhancing catalysis activity on methane activation and carbon-carbon bond coupling has been found to promote conversion and selectivity simultaneously by adding platinum–bismuth alloy cluster to form a trimetallic catalyst on zeolite (Pt-Bi/Mo/ZSM-5). This bimetallic alloy cluster has synergistic interaction with molybdenum: the formed CH3* from Mo2C on the external surface of zeolite can efficiently move on for C-C coupling on the surface of Pt-Bi particle to produce C2 compounds, which are the key intermediates of oligomerization. This pathway is parallel with the catalysis on Mo inside the cage. This catalyst demonstrated 18.7% methane conversion and 69.4% benzene selectivity at 710 °C. With 95% methane/5% nitrogen feedstock, it exhibited robust stability with slow deactivation rate of 9.3% after 2 h and instant recovery of 98.6% activity after regeneration in hydrogen. The enhanced catalytic activity is strongly associated with synergistic interaction with Mo and ligand effects of alloys by extensive mechanism studies and DFT calculation.

Prediction Challenge: Simulating Rydberg photoexcited cyclobutanone with surface hopping dynamics based on different electronic structure methods.

This research examines the nonadiabatic dynamics of cyclobutanone after excitation into the n → 3s Rydberg S2 state. It stems from our contribution to the Special Topic of the Journal of Chemical Physics to test the predictive capability of computational chemistry against unseen experimental data. Decoherence-corrected fewest-switches surface hopping was used to simulate nonadiabatic dynamics with full and approximated nonadiabatic couplings. Several simulation sets were computed with different electronic structure methods, including a multiconfigurational wavefunction [multiconfigurational self-consistent field (MCSCF)] specially built to describe dissociative channels, multireference semiempirical approach, time-dependent density functional theory, algebraic diagrammatic construction, and coupled cluster. MCSCF dynamics predicts a slow deactivation of the S2 state (10ps), followed by an ultrafast population transfer from S1 to S0 (<100fs). CO elimination (C3 channel) dominates over C2H4 formation (C2 channel). These findings radically differ from the other methods, which predicted S2 lifetimes 10-250 times shorter and C2 channel predominance. These results suggest that routine electronic structure methods may hold low predictive power for the outcome of nonadiabatic dynamics.

An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation

Slow deactivation is a critical property of voltage-gated K+ channels encoded by the human Ether-à-go-go-Related Gene 1 (hERG). hERG1 channel deactivation is modulated by interactions between intracellular N-terminal Per-Arnt-Sim (PAS) and C-terminal cyclic nucleotide-binding homology (CNBh) domains. The PAS domain is multipartite, comprising a globular domain (gPAS; residues 26–135) and an N-terminal PAS-cap that is further subdivided into an initial unstructured “tip” (residues 1–12) and an amphipathic α-helical region (residues 13–25). Although the PAS-cap tip has long been considered the effector of slow deactivation, how its position near the gating machinery is controlled has not been elucidated. Here, we show that a triad of hydrophobic interactions among the gPAS, PAS-cap α helix, and the CNBh domains is required to support slow deactivation in hERG1. The primary sequence of this “hydrophobic nexus” is highly conserved among mammalian ERG channels but shows key differences to fast-deactivating Ether-à-go-go 1 (EAG1) channels. Combining sequence analysis, structure-directed mutagenesis, electrophysiology, and molecular dynamics simulations, we demonstrate that polar serine substitutions uncover an intermediate deactivation mode that is also mimicked by deletion of the PAS-cap α helix. Molecular dynamics simulation analyses of the serine-substituted channels show an increase in distance among the residues of the hydrophobic nexus, a rotation of the intracellular gating ring, and a retraction of the PAS-cap tip from its receptor site near the voltage sensor domain and channel gate. These findings provide compelling evidence that the hydrophobic nexus coordinates the respective components of the intracellular gating ring and positions the PAS-cap tip to control hERG1 deactivation gating.

Stretch response of the mechano-gated channel TMEM63A in membrane patches and single cells.

The recently discovered ion channel TMEM63A has biophysical features distinctive for mechano-gated cation channels, activating at high pressures with slow kinetics while not inactivating. However, some biophysical properties are less clear, including no information on its function in whole cells. The aim of this study is to expand the TMEM63A biophysical characterization and examine the function in whole cells. Piezo1-knockout HEK293T cells were cotransfected with human TMEM63A and green fluorescent protein (GFP), and macroscopic currents in cell-attached patches were recorded by high-speed pressure clamp at holding voltages from -120 to -20 mV with 0-100 mmHg patch suction for 1 s. HEK293 cells cotransfected with TMEM63A and GCaMP5 were seeded onto polydimethylsiloxane (PDMS) membrane, and the response to 3-12 s of 1%-15% whole cell isotropic (equi-biaxial) stretch induced by an IsoStretcher was measured by the change in intracellular calcium ([Ca2+]i) and presented as (ΔF/F0 > 1). Increasing patch pressures activated TMEM63A currents with accelerating activation kinetics and current amplitudes that were pressure dependent but voltage independent. TMEM63A currents were plateaued within 2 s, recovered quickly, and were sensitive to Gd3+. In whole cells stretched on flexible membranes, radial stretch increased the [Ca2+]i responses in a larger proportion of cells cotransfected with TMEM63A and GCaMP5 than GCaMP5-only controls. TMEM63A currents are force activated and voltage insensitive, have a high threshold for pressure activation with slow activation and deactivation, and lack inactivation over 5 s. TMEM63A has the net polarity and kinetics that would depolarize plasma membranes and increase inward currents, contributing to a sustained [Ca2+]i increase in response to high stretch.NEW & NOTEWORTHY TMEM63A has biophysical features distinctive for mechano-gated cation channels, but some properties are less clear, including no functional information in whole cells. We report that pressure-dependent yet voltage-independent TMEM63A currents in cell membrane patches correlated with cell size. In addition, radial stretch of whole cells on flexible membranes increased the [Ca2+]i responses more in TMEM63A-transfected cells. Inward TMEM63A currents in response to high stretch can depolarize plasma membranes and contribute to a sustained [Ca2+]i increase.

Two-Dimensional Zeolites-Potential Catalysts for Biomass Valorization.

Valorization of biomass and biomass-derived molecules has become a viable route to get fuels and useful chemicals as fossil feedstocks are dwindling and the demand for renewable feedstocks and sustainable energy sources are rising. Zeolites have been promising catalysts for biomass conversion owing to their structural features and active sites. However, the use of conventional zeolites was limited due to molecular diffusion constraints, which paved the way for the emergence of two-dimensional (2D) zeolites. The high external surface area, bimodal porosity (micropores and mesopores), and 2D structure of these zeolites envisage smooth diffusion of bulky molecules, enhanced accessibility to active sites, and slow deactivation, which are benefits in the valorization of biomass. In this brief review, current advancements in the use of layered 2D zeolites for biomass conversions are discussed. The relationship between the structural features and the catalytic potential of 2D zeolites in some of the major biomass conversion processes like pyrolysis, hydrodeoxygenation, alkylation, acetalization, condensation, and dehydration is discussed and multistep reactions that proceed via a cascade mechanism are highlighted.

Experimental investigation of NO reduction by H2 on Pd using planar laser-induced fluorescence

This study investigates the NO reduction by H2 on a Pd/Al2O3 catalyst in a temperature range of 100–300 °C and NO/H2 ratios from 0.5–2, aiming to gain a deeper understanding of the reaction kinetics and its interaction with mass transfer. Planar laser-induced fluorescence (PLIF) is used to visualize the NO distributions over the catalyst, supplemented by end-of-pipe gas analysis of other components. The reduced Pd-based catalyst undergoes a slow deactivation after exposure to the reactive flow, leading to reduced overall NO conversion and decreased selectivity towards N2. The NO-PLIF measurements are only conducted on the reduced catalyst without considering the temporal evolutions. Despite the overall NO conversion varying only around 50%–65% across all the investigated conditions, the spatially resolved NO distributions reveal three distinct regimes that limit the overall NO conversion: the regime governed by intrinsic reaction rates, the regime constrained by H2 availability, and the regime restricted by NO diffusion. These findings, demonstrating the interaction between reaction kinetics and mass transfer over a heterogeneous catalyst, highlight the significance of analyzing spatially resolved concentration distributions obtained through PLIF measurements. This approach complements the conventional end-of-pipe analysis, offering a more comprehensive understanding of the underlying processes.

Nanoscale Intertwined Biphase Nanofiber as Active and Durable Air Electrode for Solid Oxide Electrochemical Cells

The poor temperature activity and durability due to surface Sr segregation are two main challenges restricting the practicability of state-of-the-art La1–xSrxCo1–yFeyO3 (LSCF) air electrodes for solid oxide electrochemical cells (SOCs). This article reports the recent discovery to unleash the constraints of performance and stability by constructing a novel nanofiber air electrode consisting of a LSCF host and GDC guest in nanoscale intertwined moiety (LSCF/GDC NF). The electrical conductivity relaxation and distribution of relaxation time results collectively disclosed the boosted surface oxygen exchange rate by two orders of magnitude at moderate SOC operation conditions (600 °C), as compared to commercial LSCF (1.01 × 10–3 cm s–1 vs 4.1 × 10–5 cm s–1). As a result, the electrochemical performance was synchronically promoted by over 5-fold (0.12 Ω·cm2 vs 0.64 Ω·cm2). Moreover, the interval stability test over 200 h in switching atmospheres (air/H2O/CO2) buttresses the superb robustness of LSCF/GDC NF with an extremely slow deactivation rate of 1.79 × 10–6 Ω·cm2 h–1 and nondetectable top-surface Sr segregation, collectively affirmed by X-ray photoelectron spectroscopy and low-energy ion scattering spectra. At atomic scale, the operando X-ray diffraction results preliminarily unravel that the formation of intertwined moiety employs the compressive strain on LSCF, which maintains the length of Sr–O against thermoinduced elongation. In addition, systemically, XPS and density functional theory simulation results prove the thermodynamically favored formation of oxygen vacancies at the biphase boundary in LSCF/GDC NF and raised the energy barrier for the formation of an intrinsic vacant Sr site. This study provides a practical and facile strategy to engineer the air electrode with enhanced performance and durability.

1-Butanol dehydration and oxidation over vanadium phosphate catalysts

The transformation of 1-butanol into either butenes or maleic anhydride was carried out both with and without oxygen, using V/P/O catalysts. With vanadyl pyrophosphate prepared by coprecipitation, at temperature lower than 240 °C and without oxygen, selectivity to butenes was higher than 90%, but a slow deactivation took place. At temperature higher than 300 °C and in the presence of air, maleic and phthalic anhydrides were the prevailing products, with selectivity of 60% and 14%, respectively. Catalytic performance was affected by crystallinity and acidity. αI-VOPO4 showed a poor performance in the absence of air, with a quick deactivation due to coke accumulation; but it displayed an excellent selectivity to butenes (close to 98%) at temperatures lower than 320 °C in the presence of air, with stable performance. At temperature higher than 360 °C, α I-VOPO4 was reduced to vanadyl pyrophosphate and catalyzed the direct oxidation of 1-butanol into maleic anhydride, but with 35% selectivity.

PO-04-166 DISTURBED PH CONTROL BY A NOVEL SLC4A3 VARIANT IDENTIFIED IN A SHORT QT SYNDROME FAMILY WITH A KCNH2 VARIANT

Short QT syndrome (SQTS) is one of the inherited primary arrhythmia syndromes and characterized by shortened QT intervals leading to ventricular fibrillation (VF) and sudden cardiac death, especially in young people. The major cause of SQTS is pathogenic variants in KCNH2 encoding Kv11.1 which produce IKr. Recently, a novel variant in SLC4A3 encoding the anion exchanger (AE3) has been identified in two SQTS families. However, the pathogenesis of SQTS caused by SLC4A3 variants in the presence of a KCNH2 variant have not been elucidated yet. We aimed to elucidate the functional change of a novel SLC4A3 variant in the interaction with a KCNH2 variant. We performed targeted gene sequencing (TGS) and whole exome sequencing (WES) in SQTS patients. Electrophysiological characteristics of the KCNH2 variant were analyzed using HEK293 cells by patch-clamp methods. We constructed stable HEK293 cell lines expressing SLC4A3 with or without the variant and measured intracellular pH (pHi) by ratiometric pH indicator, BCECF-AM. Using the stable cell lines, we transfected KCNH2 (WT or the variant), KCNQ1 and KCNJ2 and measured IKr, IKs and IK1. We identified a KCNH2 variant, c.280 c>t, p.H70Y by TGS in a 25-year-old man who suffered VF at night and was diagnosed with SQTS after resuscitation. We first performed electrophysiological analysis of KCNH2-H70Y alone, however, the variant affected a little of Ikr properties. Therefore, we performed WES in the proband and his family, and a novel SLC4A3 variant, c.1059 c>a, p.N353K was identified. Both variants were co-segregated in his family with short QT intervals. In the live cell imaging analysis, cells expressing SLC4A3-N353K showed significantly slower pHi alternations than those with WT (figure A), reflecting the loss-of-function effect of exchange kinetics in mutant AE3. In the electrophysiological analysis using stable cell lines expressing SLC4A3, IKs and IK1 did not show any changes in channel properties regardless the presence of SLC4A3-N353K. However, IKr with H70Y showed significantly slow deactivation time constant in the cells expressing SLC4A3-N353K (Figure B and C), which means the gain-of-function effect on Kv11.1. SLC4A3-N353K showed slower alteration of pHi, a loss-of-function effect on AE3. With the expression of SLC4A3-N353K,KCNH2-H70Y decelerated the deactivation kinetics of Ikr, which may lead to shortening of QT intervals in our patient.

Functional properties of GABAA receptors of AII amacrine cells of the rat retina.

Amacrine cells are a highly diverse group of inhibitory retinal interneurons that sculpt the responses of bipolar cells, ganglion cells, and other amacrine cells. They integrate excitatory inputs from bipolar cells and inhibitory inputs from other amacrine cells, but for most amacrine cells, little is known about the specificity and functional properties of their inhibitory inputs. Here, we have investigated GABAA receptors of the AII amacrine, a critical neuron in the rod pathway microcircuit, using patch-clamp recording in rat retinal slices. Puffer application of GABA evoked robust responses, but, surprisingly, spontaneous GABAA receptor-mediated postsynaptic currents were not observed, neither under control conditions nor following application of high-K+ solution to facilitate release. To investigate the biophysical and pharmacological properties of GABAA receptors in AIIs, we therefore used nucleated patches and a fast application system. Both brief and long pulses of GABA (3 mM) evoked GABAA receptor-mediated currents with slow, multi-exponential decay kinetics. The average weighted time constant (τw) of deactivation was ~163 ms. Desensitization was even slower, with τw ~330 ms. Non-stationary noise analysis of patch responses and directly observed channel gating yielded a single-channel conductance of ~23 pS. Pharmacological investigation suggested the presence of α2 and/or α3 subunits, as well as the γ2 subunit. Such subunit combinations are typical of GABAA receptors with slow kinetics. If synaptic GABAA receptors of AII amacrines have similar functional properties, the slow deactivation and desensitization kinetics will facilitate temporal summation of GABAergic inputs, allowing effective summation and synaptic integration to occur even for relatively low frequencies of inhibitory inputs.

Alumina-supported cobalt catalysts in the hydrogenation of CO2 at atmospheric pressure

20 wt.% cobalt catalysts supported on pure and 5 wt.% silica-containing alumina have been prepared and characterized by X-Ray Diffraction, IR and DR-UV-vis-NIR spectroscopies and Field-Emission Scanning Electron Microscopy (FE-SEM). The presence of a cobalt-containing surface spinel phase Co3-xAlxO4 and, for the silica-containing sample, of a segregated Co3O4 phase is evident. These catalysts have been tested in CO2 hydrogenation at atmospheric pressure in steady state conditions in the temperature range 523–773 K. Both catalysts are active in CO2 hydrogenation to methane (methanation) and to CO (reverse Water Gas Shift, rWGS). CO2 hydrogenation activity is higher on freshly pre-reduced silica-free Co/Al2O3, while selectivity to methane is slightly higher on the silica-containing sample. Spent catalysts contain clustered or amorphous cobalt metal centers as active sites for methanation. The silica-containing catalyst shows slow deactivation in CO2 hydrogenation upon 13 h experiments, with quite stable or even slightly increasing rWGS activity and decreasing CH4 selectivity. This confirms previous data suggesting that, over cobalt catalysts, sites for methanation are metal centers prone to deactivation by carbon deposition. However, in contrast with what happens with unsupported and silica-supported cobalt catalysts, where deactivation is very fast, over these alumina-based catalysts carbon deposition and deactivation occur much more slowly. Sites for rWGS are unreduced cobalt centers which do not undergo such a deactivation phenomenon.

Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate.

The opening and closing of voltage-dependent potassium channels is dependent on a tight coupling between movement of the voltage sensing S4 segments and the activation gate. A specific interaction between intracellular amino- and carboxyl-termini is required for the characteristically slow rate of channel closure (deactivation) of hERG1 channels. Compounds that increase hERG1 channel currents represent a novel approach for prevention of arrhythmia associated with prolonged ventricular repolarization. RPR260243 (RPR), a quinoline oxo-propyl piperidine derivative, inhibits inactivation and dramatically slows the rate of hERG1 channel deactivation. Here we report that similar to its effect on wild-type channels, RPR greatly slows the deactivation rate of hERG1 channels missing their amino-termini, or of split channels lacking a covalent link between the voltage sensor domain and the pore domain. By contrast, RPR did not slow deactivation of C-terminal truncated hERG1 channels or D540K hERG1 mutant channels activated by hyperpolarization. Together, these findings indicate that ability of RPR to slow deactivation requires an intact C-terminus, does not slow deactivation by stabilizing an interaction involving the amino-terminus or require a covalent link between the voltage sensor and pore domains. All-atom molecular dynamics simulations using the cryo-EM structure of the hERG1 channel revealed that RPR binds to a pocket located at the intracellular ends of helices S5 and S6 of a single subunit. The slowing of channel deactivation by RPR may be mediated by disruption of normal S5-S6 interactions.

Base-acid relay catalytic upgrading of coal pyrolysis volatiles over CaO and HZSM-5 catalysts

The relay catalytic upgrading of coal pyrolysis volatiles employing different layouts of basic CaO and acidic HZSM-5 zeolite was proposed to improve the tar quality as well as alleviate catalyst deactivation. The synergistic effect is found in relay catalytic upgrading of coal pyrolysis volatiles over dual CaO and HZSM-5 catalysts system. The relay CaO-HZSM-5 layout is better compared to layouts of relay HZSM-5-CaO, mixed CaO/HZSM-5, and their independent employments. The relay CaO-HZSM-5 layout ensures the highest light fraction in tar with 70.1 % and the minimized carbon deposition over HZSM-5 while remaining a relatively high tar yield (7.8 wt %). Meanwhile, the contents of aromatics and phenols in tar increase by 221 % and 164 % compared with the blank test (without catalyst), respectively. In this scenario, CaO promotes the cracking of large molecules in tar to form more olefins and small molecules firstly, which subsequently diffuses into micropores of HZSM-5 zeolite to produce more aromatics by dehydrocyclization. In addition, the roles of pre-cracking and pre-deoxidation of volatiles over CaO reduce the possibility of the polycondensation reactions of large molecules over acidity sites of HZSM-5 zeolite, thus lowering the carbon deposition over zeolite. These findings suggest that the base-acid relay catalytic upgrading of volatiles during coal pyrolysis will be a promising strategy to increase the tar quality and slow down catalyst deactivation.

Luminescent Lanthanide Complexes for Effective Oxygen-Sensing and Singlet Oxygen Generation.

Oxygen quantification using luminescence has attracted considerable attention in various fields, including environmental monitoring and clinical analysis. Among the reported luminophores, trivalent lanthanide complexes have displayed characteristic narrow emission bands with high brightness. This bright emission is based on photo-sensitized energy transfer via organic triplet states. The organic triplet states in lanthanide complexes effectively react with the triplet oxygen, enabling oxygen quantification by lanthanide luminescence. Some TbIII and EuIII complexes with slow deactivation processes have also formed the excited state equilibrium, thus resulting in the emission-lifetime based oxygen sensing property. The combination of TbIII /EuIII emission, EuIII /SmIII emission, EuIII /ligand phosphorescence, and ligand fluorescence/ligand phosphorescence provide the ratiometric oxygen-sensing properties. Moreover, the reaction generates singlet oxygen species which exhibit numerous applications in the photo-medical field. The ligands with large π-conjugated aromatic systems, such as porphyrin, phthalocyanine, and polyaromatic compounds, induces highly efficient oxygen generation. The combination of effective luminescence with singlet-oxygen generation by the lanthanide complexes render them suitable for photo-driven theranostics. This review summarizes the research progress of lanthanide complexes with efficient oxygen-sensing and singlet-oxygen generation properties.

Mechanism of slow hERG1 channel deactivation induced by RPR260243.

The opening and closing of voltage-dependent potassium channels is dependent on a tight coupling between movement of the voltage sensing S4 segments and the activation gate. A specific interaction between intracellular amino- and carboxyl-termini is required for the characteristically slow rate of hERG1 channel deactivation. Compounds that activate hERG1 channel function represent a novel approach for prevention of arrhythmia associated with prolonged ventricular repolarization. RPR260243 (RPR), a quinoline oxo-propyl piperidine derivative activates hERG1 by dramatically slowing the rate of channel closure, a gating process called deactivation. Here we report that similar to wild-type channels, RPR greatly slows the deactivation rate of channels missing their amino-termini, or of split channels lacking a covalent link between the voltage sensor domain and the pore domain. By contrast, RPR did not slow deactivation of C-terminal truncated hERG1 channels. D540K hERG1 mutant channels are closed at −80 mV, but can be activated by pulsing to more depolarized or hyperpolarized potentials. RPR slowed the deactivation of channels that were activated by depolarization, but not by hyperpolarization. Together, these findings indicate that RPR does not slow deactivation by stabilizing an interaction involving the amino-terminus, does not require a covalent link between the voltage sensor and pore domains, but can favorably bind at the intracellular site of S5 and S6, thereby possibly delaying closure of the helix bundle crossing gate. Furthermore, we gain insights into RPRs binding mode by comparing WT and D540K modeling results.

KCNH2 encodes a nuclear-targeted polypeptide that mediates hERG1 channel gating and expression.

KCNH2 encodes hERG1, the voltage-gated potassium channel that conducts the rapid delayed rectifier potassium current (IKr) in human cardiac tissue. hERG1 is one of the first channels expressed during early cardiac development, and its dysfunction is associated with intrauterine fetal death, sudden infant death syndrome, cardiac arrhythmia, and sudden cardiac death. Here, we identified a novel hERG1 polypeptide (hERG1NP) that is targeted to the nuclei of immature cardiac cells, including hiPSC-CMs and neonatal rat cardiomyocytes. The nuclear hERG1NP immunofluorescent signal is diminished in matured hiPSC-CMs and absent from adult rat cardiomyocytes. Antibodies targeting distinct hERG1 channel epitopes demonstrated that the hERG1NP signal maps to the hERG1 distal C-terminal domain. KCNH2 deletion using CRISPR simultaneously abolished IKr and the hERG1NP signal in hiPSC-CMs. We then identified a putative nuclear localization sequence (NLS) within the distal hERG1 C-terminus, 883-RQRKRKLSFR-892. Interestingly, the distal hERG1 C-terminal domain was targeted almost exclusively to the nuclei when overexpressed HEK293 cells. Conversely, deleting the NLS from the distal peptide abolished nuclear targeting. Similarly, blocking α or β1 karyopherin activity diminished nuclear targeting. Finally, overexpressing the distal hERG1 C-terminus significantly reduced hERG1a current density and slowed deactivation, compared to cells expressing GFP. Deleting the NLS from the distal hERG1 C-terminal domain abolished the effects of the distal C-terminus on hERG1a current amplitude and kinetics. These data identify a developmentally regulated polypeptide encoded by KCNH2, hERGNP, whose presence in the nucleus indirectly modulates hERG1 current magnitude and kinetics.