Active Site Blocking Research Articles

Influence of Carboxymethyl Chitosan and Sodium Humate Composite Corrosion Inhibitor on the Corrosion Resistance of EH40 Steel in Seawater.

In this study, corrosion weight loss experiments were conducted to explore the corrosion-inhibiting properties of a composite inhibitor consisting of carboxymethyl chitosan (CMCS) and sodium humate (SH) at varying concentrations on EH40 steel in seawater. An investigation was conducted into the electrochemical behavior of EH40 steel in seawater and the mechanism of composite inhibitor consisting of carboxymethyl chitosan (CMCS) and sodium humate (SH) at varying concentrations on EH40 steel in seawater through an electrochemical test. X-ray photoelectron spectroscopy (XPS), scanning electron microscopy and energy-dispersion spectroscopy (SEM-EDS), Fourier transform infrared absorption spectroscopy (FTIR), and contact angle measurements were performed to confirm the mechanism of CMCS and SH as well as their composite corrosion inhibitors at the interface between seawater and EH40 steel. Furthermore, density functional theory (DFT) calculation supports the experimental findings. The results show that CMCS, SH, and their composite inhibitor are a mixed type of corrosion inhibitor that mainly inhibits cathodic reactions and corrosion through the active site blocking mechanisms. Their corrosion inhibition effect increases with the increase of mass concentration, and the composite inhibitor performs better in corrosion inhibition and scale inhibition than the individual inhibitor. When the CMCS mass concentration reaches 100 mg/L and the SH mass concentration reaches 50 mg/L, the corrosion inhibition rate is 74.65%, the corrosion potential shifts by about 47.39 mV, the Rp value increases from 358.6 to 1102.4 Ω·cm2, and the Ydl value decreases from 177.31 Sn Ω-1cm-2 × 10-6 to 92.672 Sn Ω-1cm-2 × 10-6. CMCS and SH are adsorbed onto the surface of EH40 steel, forming a protective film through the complexation of carboxyl, amino, and other functional groups to inhibit corrosion and prevent the further formation of scale. In addition, synergistic coadsorption occurs between CMCS and SH, and the composite corrosion inhibitor exerts a better effect than the individual corrosion inhibitor.

A self-driven microfluidic immunosensor for rapid separation, enrichment, and detection of biomarkers in serum.

Biomarkers and their concentration levels are critical indicators of metabolomics for clinical applications. Rapid and sensitive analysis methods are essential for realizing timely and efficient quantitation of those significant biomarkers. In this work, a self-driven microfluidic immunosensor was developed for rapid all-in-one separation, enrichment, and detection of biomarkers. This immunosensor was constructed from a cyclic olefin copolymer (COC) channel layer and a polydimethylsiloxane (PDMS) sensing layer. The COC channel layer was modified through protein adsorption, immobilization, and remaining active site blocking. The obtained hydrophilic microchannels not only reduce the nonspecific adsorption, but also provide stable capillary-driven flow generation with linear velocities up to 20mm/s for aqueous solution auto-injection. The PDMS sensing layer was modified using capture antibodies to accomplish affinity recognition of target biomarkers. Procalcitonin (PCT) and serum amyloid A (SAA) were selected as model biomarkers in the feasibility study on applying the self-driven microfluidic immunosensor to bioassay. The limits of detection of PCT and SAA were 7.9ng/L and 7.6μg/L, respectively. Moreover, the whole process can be accomplished within 60min with excellent selectivity and reproducibility. In clinical serum sample analysis, satisfactory recoveries were achieved for PCT and SAA in the ranges of 85.0-103.0% and 95.5-106.0%, respectively, with relative standard deviations less than 5.3%. The method accuracy was further confirmed by the results of commercial immunoassay kits. This simple and easily operated immunosensor provides a rapid and sensitive biomarker analysis tool, and promotes the further development of automated and easy-to-use microfluidic immunoassays.

An electrochemical study of iron carbonate layers formed on carbon steel during corrosion in elevated pressure CO2 environments

Iron carbonate (FeCO3) layers influence the electrochemical properties of carbon steel during aqueous corrosion in carbon dioxide–saturated environments. In this study, electrochemical measurements conducted in an autoclave at 80°C and 5 barg are combined with cross-sectional imaging to elucidate interfacial properties of X65 carbon steel at key stages of FeCO3 layer development. The effects of evolving system chemistry are also considered by variation of the X65 surface area to solution volume (A/V) ratio. FeCO3 reduces general corrosion rates through a combination of active site blocking and restriction of mass transport, with resultant layer properties dependent on the A/V ratio.

Assessment of corrosion inhibition performance of olive leaf extract mediated chitosan–Ag nanocomposites and influence of KI addition for X60 steel in acid solution

Chitosan–silver (CHT–Ag) nanocomposite (NCP) containing various dosages of chitosan (0.5, 1.0 and 2.0 g) was synthesized in-situ using olive leaf extract (OLE) as reducing and capping agent. The OLE mediated CHT–Ag NCP was characterized using UV–vis spectrometer, attenuated total reflectance-infrared spectroscopy (ATR-IR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM) techniques. The prepared NCP was assessed as corrosion inhibitor for X60 steel in 5% HCl solution using weight loss (WL) and electrochemical (electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR) and potentiodynamic polarization (PDP)) methods complemented by surface analysis of the corroded carbon steel (CS) without and with the NCPs utilizing scanning electron microscopy (SEM)/EDS, 3D optical profilometer and atomic force microscopy (AFM). The influence of adding KI on the corrosion inhibition performance of NCPs was investigated as well. TEM results indicate that CHT–Ag nanocomposites are polydisperse and spherical in shape with sizes in the range of 3.7–18.1 nm. The crystalline nature of Ag nanoparticles in the nanocomposites was confirmed by XRD and TEM examination. The prepared NCPs function as effective inhibitors for X60 CS corrosion in the acidic environment. Corrosion inhibition effect was observed to increase with rise in the NCPs concentration with the optimum inhibition efficiency (IE) obtained at the maximum dosage of 0.5% studied. The order of corrosion inhibition performance followed the trend CHT2.0 – Ag > CHT1.0 – Ag > CHT0.5 – Ag NCP. Also, IE was found to decrease with rise in temperature. The PDP data indicates that the NCPs alone and in combination with KI, reduced X60 CS corrosion via the mechanism of active site blocking effect. The addition of KI to the NCPs improves IE but not due to synergism. The surface assessment data confirms the establishment of a protective layer due to NCPs adsorption on the X60 CS surface.

Dynamically Restructuring NixCryO Electrocatalyst for Stable Oxygen Evolution Reaction in Real Seawater.

In the pursuit of long-term stability for oxygen evolution reaction (OER) in seawater, retaining the intrinsic catalytic activity is essential but has remained challenging. Herein, we developed a NixCryO electrocatalyst that manifested exceptional OER stability in alkaline condition while improving the activity over time by dynamic self-restructuring. In 1 M KOH, NixCryO required overpotentials of only 270 and 320 mV to achieve current densities of 100 and 500 mA cm-2, respectively, with excellent long-term stability exceeding 475 h at 100 mA cm-2 and 280 h at 500 mA cm-2. The combination of electrochemical measurements and in-situ studies revealed that leaching and redistribution of Cr during the prolonged electrolysis resulted in increased electrochemically active surface area. This eventually enhanced the catalyst porosity and improved OER activity. NixCryO was further applied in real seawater from the Red Sea (without purification, 1 M KOH added), envisaging that the dynamically evolving porosity can offset the adverse active site-blocking effect posed by the seawater impurities. Remarkably, NixCryO exhibited stable operation for 2000, 275 and 100 h in seawater at 10, 100 and 500 mA cm-2, respectively. The proposed catalyst and the mechanistic insights represented a step towards realization of non-noble metal-based direct seawater splitting.

Self-supporting electrocatalyst constructed from in-situ transformation of Co(OH)2 to metal-organic framework to Co/CoP/NC nanosheets for high-current-density water splitting

Transition metal phosphide (TMP) emerges as a promising electrocatalyst for overall water splitting (OWS). However, conventional TMP materials require exogenous metal ions to participate in coordination reactions, which usually suffer from active site blocking, pronounced intrinsic impedance, and inevitable catalyst shedding at high current density. Herein, a novel in-situ construction strategy has been developed to grow N-doped carbon (NC) enwrapped Co/CoP nanosheets directly onto Co foam (abbreviated as CoF) through a three-step transformation of Co to Co(OH)2 to Co-Metal-Organic Framework (Co-MOF) to Co/CoP/NC. In the entire preparation process, Co metal is only provided by the CoF substrate without external metal sources. Such in-situ construction yields tight contact at the interface of the heterogeneous catalyst, leading to much-reduced impedance and boundary vacancy, while the porous nitrogen-doped carbon backbone further endows the catalyst with the exposure of massive active sites, promotes mass transfer, and possesses high electrical conductivity. The Co/CoP/NC/CoF requires overpotentials of only 64 mV/263 mV@10 mA cm−2 and 414 mV/481 mV@400 mA cm−2 for both HER/OER in 1.0 M KOH, respectively. Remarkably, it reveals excellent OWS catalytic activity with a cell voltage of 1.56 V@10 mA cm−2 and 1.88 V@200 mA cm−2. This strategy of in-situ interface engineering transformation provides new ideas for direct device processing and construction of highly-efficient transition-metal-based OWS electrode materials.

Corrosion Inhibition Evaluation of Chitosan–CuO Nanocomposite for Carbon Steel in 5% HCl Solution and Effect of KI Addition

Chitosan–copper oxide (CHT–CuO) nanocomposite was made by an in-situ method utilizing olive leaf extract (OLE) as reductant. The OLE mediated CHT–CuO nanocomposite containing varying amount of chitosan (0.5, 1.0 and 2.0 g) was evaluated as corrosion inhibitor for X60 carbon steel in 5 wt% hydrochloric acid solution. The corrosion inhibitive performance was assessed utilizing weight loss and electrochemical impedance spectroscopy, linear polarization resistance and potentiodynamic polarization techniques complemented with surface assessment of the corroded X60 carbon steel without and with the additives using scanning electron microscopy/energy dispersive X-ray spectroscopy and 3D optical profilometer. The effect of KI addition on the corrosion protection capacity of the nanocomposites was also examined. Corrosion inhibitive effect was observed to increase with increase in the nanocomposites dosage with the highest inhibition efficiency (IE) achieved at the optimum dosage of 0.5%. The order of corrosion inhibition performance followed the trend CHT1.0–CuO (90.35%) > CHT0.5–CuO (90.16%) > CHT2.0–CuO (89.52%) nanocomposite from impedance measurements. Also, IE was found to increase as the temperature was raised from 25 to 40 °C and afterwards a decline in IE was observed with further increase in temperature to 50 and 60 °C. The potentiodynamic polarization results suggest that the nanocomposites alone and in combination with KI inhibited the corrosion of X60 carbon steel by an active site blocking mechanism. Addition of KI upgrades the IE of the nanocomposites but is not attributable to synergistic influence. The lack of synergistic influence was confirmed from the computed synergism parameter (S1) which was found to be less than unity with values of 0.89, 0.74 and 0.75 for CHT0.5–CuO, CHT1.0–CuO and CHT2.0–CuO nanocomposites, respectively, at 60 °C. Furthermore, KI addition improved the IE with rise in temperature from 25 to 60 °C. Surface analysis results confirm the formation of a protective film which could be attributed to the adsorption of the nanocomposites on the carbon steel surface.

A novel strategy for screening angiotensin-converting enzyme inhibitors from natural products based on enzyme-immobilized ligand fishing combined with active-site blocking and directional enrichment

Some natural products are important sources of treatments for hypertension based on their potential inhibitory effects on angiotensin-converting enzyme (ACE); however, it is difficult to identify natural ACE inhibitors (ACEIs) due to the complex secondary metabolite environment of natural products. Enzyme immobilization is an important method for screening active constituents in natural products, but this method can sometimes return false-positive and false-negative results. To improve the accuracy and reliability of ligand-fishing methods, we established a novel strategy based on enzyme-immobilized ligand fishing combined with active-site blocking and directional enrichment technologies. We first synthesized ACE-immobilized mesoporous magnetic beads and then verified the screened compounds by molecular docking and in vitro activity detection. We then used active-site blocking to exclude non-specific binding constituents and applied directional enrichment to enrich the low-content constituents for ligand fishing. The screening identified six potential ACEIs from Scutellariae Radix and eight potential ACEIs from Lonicerae japonicae flos, and their inhibitory activity was confirmed by molecular docking simulations and in vitro activity detection. This process screened six additional compounds and excluded two false-positive results as compared with results exclusively using enzyme immobilization. This strategy provides a feasible method for screening active compounds in natural products.

The role of defects in the photoconversion of 2-propanol on rutile titania: Operando spectroscopy combined with elementary studies

Previous studies on the reaction chemistry of 2-propanol at rutile powders in liquid phase as well as at TiO2(110) surfaces under UHV conditions, both with low reduction degree, exhibited that partial photo oxidation is observable in the presence of oxygen, however, with low yields. Here, we show that at highly reduced surfaces a partial photo oxidation of 2-propanol is not only possible in the presence of oxygen but also in coadsorption with water or even without coadsorbates below room temperature. Thermally, only the conversion towards propane and propene was observed at temperatures above 550 K. Liquid Phase experiments further showed that the coadsorbate influences the acetone yield of the partial photo oxidation. While in the presence of oxygen an increasing acetone conversion was observed, the acetone yield is reduced in the presence of water in accordance with the hypothesis of an active site blocking by water.

Pre-Coking Strategy Strengthening Stability Performance of Supported Nickel Catalysts in Chloronitrobenzene Hydrogenation

Supported nickel catalysts represent a class of important catalytic materials in selective hydrogenations, but applications are frequently limited by metal agglomeration or active-site blocking induced by the presence of hydrogen halides. Herein, we report a novel pre-coking strategy, exposing the nickel nanoparticles under methane dry reforming conditions to manipulate performance in the continuous-flow hydrogenation of 1,2-dichloro-4-nitrobenzene. Compared with the pristine nickel catalyst, the nanotube-like coke-modified nickel catalyst showed weakened hydrogenating ability, but much improved stability and slightly better selectivity to the target product, 3,4-dichloroaniline. Characterization results revealed that the strengthened stability performance can be mainly linked to the reduced propensity to retain chlorine species, which seems to block the access of the substrate molecules to the active sites, and thus is a major cause of catalyst deactivation on the pristine nickel catalyst. Coke deposition can occur on the pre-coked nickel catalyst but not on the pristine analog; however, the impact on the stability performance is much milder compared with that on chlorine uptake. In addition, the presence of coke is also beneficial in restraining the growth of the nickel nanoparticles. Generally, the developed method might provide an alternative perspective on the design of novel transition-metal-based catalytic materials for other hydrogenation applications under harsh conditions.

Evaluation of the inhibiting effect of H2O, O2, and NO on the performance of laboratory and pilot K-ZnxCo3-xO4 catalysts supported on α-Al2O3 for low-temperature N2O decomposition

The K-ZnxCo3-xO4 catalyst supported on α-Al2O3 for N2O decomposition was investigated in terms of its resistance towards typical contaminants (O2, H2O, and NO) present in the nitric acid plant tail gases. The catalyst synthesized in laboratory-scale was thoroughly characterized by means of X-ray μ-tomography, XRF, XRD, and SEM/TEM/EDX. The impact of contaminants such as O2, H2O, and NO on the N2O conversion of the catalyst was examined and quantified by kinetic and thermodynamic modeling. The mechanism of inhibition involving local (active site blocking) and global (modification of the spinel electronic properties by electrophilic NOx adspecies) effects was proposed. The strongest inhibition of NO was associated with its facile reactivity with surface O intermediates produced during N2O decomposition. The resultant NO2 and NO3 surface adducts are stable at the catalyst surface up to 550 °C. For the pilot catalyst, the effect of contamination was the same in nature as for the laboratory sample, however, the observed quantitative differences were associated with the changes in the shape of the spinel nanocrystals constituting the catalyst active phase. The obtained results provide rationales for designing and preparation of the robust deN2O catalyst with enhanced resistivity to poisoning.

Direct Observation of Carbon Dioxide Electroreduction on Gold: Site Blocking by the Stern Layer Controls CO2 Adsorption Kinetics.

Directly observing active surface intermediates represents a major challenge in electrocatalysis, especially for CO2 electroreduction on Au. We use in-situ, plasmon-enhanced vibrational sum frequency generation spectroscopy, which has detection limits of <1% of a monolayer and can access the Au/electrolyte interface during active electrocatalysis in the absence of mass transport limitations. Measuring the potential-dependent surface coverage of atop CO confirms that the rate-determining step for this reaction is CO2 adsorption. An analysis of the interfacial electric field reveals the formation of a dense cation layer at the electrode surface, which is correlated to the onset of CO production. The Tafel slope increases in conjunction with the field saturation due to active site blocking by adsorbed cations. These findings show that CO2 reduction is extremely sensitive to the potential-dependent structure of the electrochemical double layer and provides direct observation of the interfacial processes that govern these kinetics.

Single-atom cobalt array bound to distorted 1T MoS2 with ensemble effect for hydrogen evolution catalysis

The grand challenge in the development of atomically dispersed metallic catalysts is their low metal-atom loading density, uncontrollable localization and ambiguous interactions with supports, posing difficulty in maximizing their catalytic performance. Here, we achieve an interface catalyst consisting of atomic cobalt array covalently bound to distorted 1T MoS2 nanosheets (SA Co-D 1T MoS2). The phase of MoS2 transforming from 2H to D-1T, induced by strain from lattice mismatch and formation of Co-S covalent bond between Co and MoS2 during the assembly, is found to be essential to form the highly active single-atom array catalyst. SA Co-D 1T MoS2 achieves Pt-like activity toward HER and high long-term stability. Active-site blocking experiment together with density functional theory (DFT) calculations reveal that the superior catalytic behaviour is associated with an ensemble effect via the synergy of Co adatom and S of the D-1T MoS2 support by tuning hydrogen binding mode at the interface.

Isozymes inhibited by active site blocking: versatility of calcium indifferent hesperidin binding to phospholipase A2 and its significance

sPLA2 is released under inflammatory conditions from neutrophils, basophils and T-cells. They cleave the cellular phospholipids leading to the release of arachidonic acid and there by provide intermediates for biosynthesis of inflammatory mediators. The focus of this study is on the interaction of hesperidin, a natural flavonoid with Group IB, IIA, and V and X isozymes of sPLA2. Affinity of hesperidin towards PLA2 isozymes was analyzed through enzymatic studies and molecular modeling. The experiments showed that hesperidin competitively inhibited PLA2 with IC50 of 5.1 µM. Molecular modeling studies revealed the association of hesperidin with the docking scores −6.90, −9.53, −5.63 and −8.29 kcal for isozymes Group IB, IIA, V and X of PLA2 respectively. Their binding energy values were calculated as −20.25, −21.63, −21.66 and −33.43 kcal for the Group IB, IIA, V and X respectively. Structural model for Group V was made by homology modeling since no structural coordinates were available. Molecular dynamics studies were carried out to evaluate the structural stability of protein ligand complex. The analyses showed that hesperidin blocked the entry of the substrate to the active site of PLA2 and it was indifferent to the differences of the isozymes. Hence, hesperidin might serve as lead for designing highly specific anti-inflammatory drugs directed to the PLA2 isozyme specific to various diseases, with IC50 value of therapeutic significance.

In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea.

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3-O-gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative properties. Furthermore, several lines of evidence have indicated that the binding affinity of EGCG to specific proteins may explain its mechanism of action. This review article aims to reveal how EGCG-protein interactions can explain the mechanism by which green tea/EGCG can exhibit health beneficial effects. We conducted a literature search, using mainly the PubMed database. The results showed that several methods such as dot assays, affinity gel chromatography, surface plasmon resonance, computational docking analyses, and X-ray crystallography have been used for this purpose. These studies have provided evidence to show how EGCG can fit or occupy the position in or near functional sites and induce a conformational change, including a quaternary conformational change in some cases. Active site blocking, steric hindrance by binding of EGCG near an active site or induced conformational change appeared to cause inhibition of enzymatic activity and other biological activities of proteins, which are related to EGCG’s biological oligomer and formation of their toxic aggregates, leading to the prevention of neurodegenerative diseases and amyloidosis. In conclusion, these studies have provided useful information on the action of green tea/catechins and would lead to future studies that will provide further evidence for rational EGCG therapy and use EGCG as a lead compound for drug design.

Chromogenic substrates as fundamental tool to design new thrombin inhibitors. Determination of inhibition equilibrium constants.

The structure-activity relationship of dipetalogastin II, the strongest thrombin inhibitor isolated and cloned from the bug Dipetalogaster maximus, was examined by introducing gradual changes into the molecule by means of molecular biological methods. The effect upon its inhibition equilibrium constant was determined after each change by a chromogenic assay. This structural information was fundamental to design new dipetalogastin II-derived inhibitors. Our results suggested that the acidic sequence DEHDHDFEDT corresponding to amino acid residues 49 to 58 of dipetalogastin II reacts with the anion binding exosite (ABE) 1 of thrombin. Based on this finding, we constructed a chimeric molecule consisting of the active site blocking segment of dipetalogastin II (amino acid residues 1 to 48) and the ABE 1 blocking segment of hirudin. This construct showed better thrombin inhibitory activity than both separated segments only after the introduction of a glycine linker between both blocking segments. We thus obtained a thrombin inhibitor called dipetarudin with an inhibition equilibrium constant comparable to that of dipetalogastin II and a molecular mass below that of dipetalogastin.

NOx and propene conversion on La0.85Sr0.15MnO3+d/Ce0.9Gd0.1O1.95 symmetrical cells

&lt;p class="PaperAbstract"&gt;&lt;span lang="EN-US"&gt;The catalytic electrochemical reduction of NO with propene was investigated on La&lt;sub&gt;0.85&lt;/sub&gt;Sr&lt;sub&gt;0.15&lt;/sub&gt;MnO&lt;sub&gt;3+d&lt;/sub&gt;/Ce&lt;sub&gt;0.9&lt;/sub&gt;Gd&lt;sub&gt;0.1&lt;/sub&gt;O&lt;sub&gt;1.95&lt;/sub&gt; symmetrical cells. The electrodes were infiltrated with BaO and Pt. The cells were catalytically active towards the selective catalytic reduction of NO&lt;sub&gt;x&lt;/sub&gt; with propene, but BaO infiltration lowered the NO conversion, probably because of active-site blocking on La&lt;sub&gt;0.85&lt;/sub&gt;Sr&lt;sub&gt;0.15&lt;/sub&gt;MnO&lt;sub&gt;3+d&lt;/sub&gt;. Pt infiltration enhanced the reduction of NOx with propene. When a voltage was applied to the cell with BaO infiltrated electrodes, the NO conversion increased in absence and presence of propene in the feed gas and presence of 10&lt;/span&gt;&lt;span lang="EN-US"&gt;% O&lt;sub&gt;2&lt;/sub&gt;. The addition of propene into the feed gas did not enhance the conversion of NO when the electrodes were infiltrated with BaO. When platinum was co-infiltrated with BaO, the catalytic activity towards the reduction of NO with propene was enhanced. However, almost no effect was observed when a voltage was applied. Additionally, when the cells were infiltrated with Pt, an electrochemical promotion was observed with respect to CO&lt;sub&gt;2&lt;/sub&gt; formation.&lt;/span&gt;&lt;/p&gt;

Inhibition of Plasma Kallikrein by a Highly Specific Active Site Blocking Antibody

Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.

Insights into CO poisoning in high performance proton-conducting solid oxide fuel cells

High performance anode supported proton-conducting solid oxide fuel cells (PC-SOFC) were fabricated and their performance in syngas was studied. PC-SOFC button cells produced a maximum power density of 812 mW cm−2 in H2 at 750 °C. It was found that the CO-containing feed streams could drastically degrade the performance of PC-SOFC. Based on the experimental results and the theoretical analysis, the detailed process of the CO-induced Ni catalyst deactivation was identified. This process could be divided into three distinguishable stages during the continuous exposure of the Ni catalyst in the CO-containing environment. The first stage could be described using the CO surface active site blocking mechanism, which was further confirmed by CO/H2 competitive adsorption model. The second stage deactivation was proposed to be related to the carbon deposition at TPB (Triple-phase Boundary). The deactivation during this stage was accelerated by the electrochemical conversion of H2. The last stage was attributed to the coking of Ni catalyst and the resulted metal dusting effect.

Structural Context of Disease-Associated Mutations and Putative Mechanism of Autoinhibition Revealed by X-Ray Crystallographic Analysis of the EZH2-SET Domain

The enhancer-of-zeste homolog 2 (EZH2) gene product is an 87 kDa polycomb group (PcG) protein containing a C-terminal methyltransferase SET domain. EZH2, along with binding partners, i.e., EED and SUZ12, upon which it is dependent for activity forms the core of the polycomb repressive complex 2 (PRC2). PRC2 regulates gene silencing by catalyzing the methylation of histone H3 at lysine 27. Both overexpression and mutation of EZH2 are associated with the incidence and aggressiveness of various cancers. The novel crystal structure of the SET domain was determined in order to understand disease-associated EZH2 mutations and derive an explanation for its inactivity independent of complex formation. The 2.00 Å crystal structure reveals that, in its uncomplexed form, the EZH2 C-terminus folds back into the active site blocking engagement with substrate. Furthermore, the S-adenosyl-L-methionine (SAM) binding pocket observed in the crystal structure of homologous SET domains is notably absent. This suggests that a conformational change in the EZH2 SET domain, dependent upon complex formation, must take place for cofactor and substrate binding activities to be recapitulated. In addition, the data provide a structural context for clinically significant mutations found in the EZH2 SET domain.