Occupation Of Active Sites Research Articles

One-Pot Synthesis of (CrMnFeCoNi)Ox High-Entropy Oxides for Efficient Catalytic Oxidation of Propane: A Promising Substitute for Noble Metal Catalysts.

The efficient catalytic oxidation of propane, as a short-chain alkane, remains challenging in environmental catalysis. High-entropy oxides (HEOs) exhibit advantages in abundant and well-dispersed elemental composition, exceptional thermal stability, and enriched lattice defects. Herein, (CrMnFeCoNi)Ox HEO catalysts are successfully synthesized by using a continuous hydrothermal flow synthesis (CHFS) route, without any subsequent calcination processes. This route yields HEOs with fine particle sizes, high specific surface areas, and abundant near-surface lattice oxygen compared to the traditional coprecipitation method. Notably, the propane conversion over the CHFS-made (CrMnFeCoNi)Ox HEO reaches 90% at 255 °C, with an apparent activation energy of 53.2 kJ/mol, mainly attributed to its enriched lattice oxygen and enhanced oxygen mobility that prevent the accumulation of acetates and the consequent occupation of active sites. In comparison to commercial Pt/Al2O3 and Pd/Al2O3, (CrMnFeCoNi)Ox HEO demonstrates exceptional activity and can maintain long-term stability under high-temperature (upon 650 °C) and moisture-rich conditions (at 2-10 vol %). These attributes highlight its potential as a promising substitute for noble metal catalysts in industrial applications.

Integrating Molecular Dynamics and Machine Learning Algorithms to Predict the Functional Profile of Kinase Ligands.

The modulation of protein function via designed small molecules is providing new opportunities in chemical biology and medicinal chemistry. While drugs have traditionally been developed to block enzymatic activities through active site occupation, a growing number of strategies now aim to control protein functions in an allosteric fashion, allowing for the tuning of a target's activation or deactivation via the modulation of the populations of conformational ensembles that underlie its function. In the context of the discovery of new active leads, it would be very useful to generate hypotheses for the functional impact of new ligands. Since the discovery and design of allosteric modulators (inhibitors/activators) is still a challenging and often serendipitous target, the development of a rapid and robust approach to predict the functional profile of a new ligand would significantly speed up candidate selection. Herein, we present different machine learning (ML) classifiers to distinguish between potential orthosteric and allosteric binders. Our approach integrates information on the chemical fingerprints of the ligands with descriptors that recapitulate ligand effects on protein functional motions. The latter are derived from molecular dynamics (MD) simulations of the target protein in complex with orthosteric or allosteric ligands. In this framework, we train and test different ML architectures, which are initially probed on the classification of orthosteric versus allosteric ligands for cyclin-dependent kinases (CDKs). The results demonstrate that different ML methods can successfully partition allosteric versus orthosteric effectors (although to different degrees). Next, we further test the models with FDA-approved CDK drugs, not included in the original dataset, as well as ligands that target other kinases, to test the range of applicability of these models outside of the domain on which they were developed. Overall, the results show that enriching the training dataset with chemical physics-based information on the protein-ligand dynamic cross-talk can significantly expand the reach and applicability of approaches for the prediction and classification of the mode of action of small molecules.

Adsorption dynamics of gaseous toluene with and without formaldehyde and water vapors on composites of UiO-66-NH2 and microporous carbon

To improve the adsorption capacity/selectivity of activated carbon (AC) against diverse volatile organic compounds (VOCs), a series of AC-based composites have been prepared with UiO-66-NH2 (U6N) and coded as AC-U6Nx (x = 1–20 wt/wt%). The adsorption potential of AC-U6Nx is evaluated against toluene in relation to the effects of composite compositions and the presence of competing feed gases/vapors (e.g., formaldehyde (FA) and water vapor). Although AC-U6N(1%) adsorbs toluene preferentially over FA, the selectivity factor of the former decreases from 6.4 to 2.63 as the x value increases from 1 to 20 wt%. This indicates the crucial role of U6N-NH2 groups in active capturing of FA over toluene through Schiff-base adsorption mechanism. Interestingly, the partition coefficient (PC100%: 0.045 ± 0.004 mol kg−1 Pa−1) of AC-U6N(1%) for 100 ppm FA remains nearly constant across varying toluene levels (1–100 ppm), suggesting the preferential occupation of active sites by FA (pore-filling). The contrasting role of relative humidity (RH) is also evidenced, as AC-U6N(1%), exhibits the highest capacity for toluene and FA under dry (0 % RH) and humid (20 % RH) conditions, respectively. The adsorption behavior of VOC on AC-U6N(1%) surface active sites (e.g., graphitic basal planes, NH2, COO–, and Zr sites) is predictable with a good fit of experimental data to the Freundlich isotherm and pseudo-second-order (PSOM) kinetic models. A density functional theory (DFT) simulation supports the enhancement of toluene adsorption on the interface of AC and U6N-based systems. Overall, this work offers practical guidelines for the construction of advanced functional adsorbents against diverse VOCs under both competitive and non-competitive conditions.

Peanut-shell-derived biochar mediated peracetic acid activation for the elimination of acetaminophen via an electron-transfer regime

Biochar-based heterogeneous activation of disinfectant peracetic acid (PAA) is an attractive and promising route for micropollutant elimination in water, yet the underlying activation mechanism is still scarce. In this study, PAA was first catalyzed by peanut shell-derived biochar (PSBC) to degrade acetaminophen (ACP). The enhancement of ACP removal was triggered by PAA activation, while the coexisted H2O2 was unexpected to be an adverse factor owing to its occupation of active sites. Higher dosages of PSBC (0–0.30 g/L) and PAA (0–4.0 mM) favored the destruction of ACP, and the activation energy (41.8 kJ/mol) of PSBC/PAA system is lower than that of the thermal or microwave activated PAA system. The experimental results demonstrate that the metastable complex PSBC-PAA* dominated ACP elimination through an electron transfer mechanism. The surface –OH group was validated to be the key active site for PAA activation. Surprisingly, the actual water matrices present a negligible effect and the promotion of HCO3− ion on ACP removal was even observed. Based on the identified intermediates, the transformation of ACP was further proposed with the formation of polymeric products via oxidative coupling reactions. The findings not only shed light on the mechanism of PAA activated by the biochar-based catalyst but also contribute to a novel perspective on future PAA studies in contamination remediation.

MnO2 enhanced low temperature HCHO sensing performance of SnO2

The exploration of gas sensing materials holds significant importance for practical applications. This work introduces a novel SnO2/MnO2 nanocomposite designed to achieve formaldehyde monitoring at ppb level with a relative low temperature. The as prepared sensor demonstrates a response of 8.1–50 ppb formaldehyde at 100 °C. These remarkable formaldehyde sensing capabilities were explained by the heterojunction structure of the composite, and the low-temperature catalytic properties of MnO2. Moreover, in-situ infrared reflectance spectroscopy was employed to investigate the underlying mechanism by monitoring the evolution of reaction intermediates, and the result suggested that the addition of MnO2 can reduce the ineffective occupation of active sites and promote the generation of intermediate intermediates.

Co3O4 (111) surfaces in contact with water: molecular dynamics study of the surface chemistry and structure at room temperature.

In this work, we have used ab initio molecular dynamics at room temperature to study the adsorption and dissociation of a thin water film on Co3O4 (111) surfaces, considering the O-rich and Co-rich terminations named as the A-type and B-type surface terminations, respectively. We investigate the occupation of active sites, the hydrogen bond network at the interface and the structural response of the surfaces to water adsorption. On both terminations, water adsorbs via a partial dissociative mode. The contact layer is populated by molecular water as well as OH groups and surface OH resulting from proton transfer to the surface. The B-termination is more reactive, with a higher degree of dissociation in the contact layer with water (46%). On the B-terminated surface, water barely adsorbs on the Co2+ sites and almost exclusively binds and dissociates on the Co3+ sites. The interaction with the surface consists mostly of Co3+-Ow bonds and proton transfer exclusively to the 3-fold unsaturated surface Os1. Hydrogen bonds between water molecules in the aqueous film dominate the hydrogen bond network and no hydrogen bonds between water and the surface are observed. The A-terminated surface is less reactive. Water binds covalently on Co2+ sites, with a dissociation degree of 13%. Proton transfer occurs mostly on the 3-fold unsaturated surface oxygens Os1. Besides, short-lived surface OH arising from proton transfer to 3-fold unsaturated surface oxygens Os2 is observed. H-bonding to surface Os1 and Os2 constitutes 12.7% and 19.8% of the H-bond network, respectively, and the largest contribution is found among the water molecules (67.4%). On both surfaces, the coordination number of the active sites drives the relaxations of the outermost atom positions to the their bulk counterparts. The occupation of active sites on B-termination could reach up to 3 adsorbates per Co3+ leading to a binding motif in which the Co is octahedrally coordinated and which was observed experimentally.

Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.

Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, the latter has been suggested by symmetry in most of the 500 reported protease/ligand complex structures solved by macromolecular crystallography (MX). Here we apply the latter to both covalent and noncovalent ligands in complex with Mpro. Strikingly, our experiments show that the occupation of both active sites of the dimer originates from an excess of ligands. Indeed, cocrystals obtained using a 1:1 ligand/protomer stoichiometry lead to single occupation only. The empty binding site exhibits a catalytically inactive geometry in solution, as suggested by molecular dynamics simulations. Thus, Mpro operates through negative cooperativity with the asymmetric activity of the catalytic sites. This allows it to function with a wide range of substrate concentrations, making it resistant to saturation and potentially difficult to shut down, all properties advantageous for the virus' adaptability and resistance.

Unraveling a Combined Inactivation Mechanism of Cytochrome P450s by Genipin, the Major Reactive Aglycone Derived from Gardeniae Fructus.

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.

Electronic and Coordination Effect of PtPd Nanoflower Alloys for the Methanol Electrooxidation Reaction

Platinum-based electrocatalysts usually exhibit limited and quickly vanished activity for the methanol oxidation reaction (MOR) due to active site occupation and surface intermediate poisoning, especially CO. The attendant synergistic effect of the alloy strategy is often executed to improve these flaws. Here, PtPd nanoflower alloys uniformly anchored on the carbon paper were successfully synthesized by electrodeposition to construct well-defined active sites, over which high MOR activity and tolerance were realized. The homogeneous alloy structure of PtPd nanoflowers was confirmed by TEM and XAFS. Impressively, the Pt1Pd1-N NFs/CP exhibited an excellent mass activity of 9.25 A mgPt+Pd–1 and specific activity of 13.2 mA cmECSA–2 of MOR in the alkaline electrolyte, and 87.8% of the initial activity was still retained after 500 cycles. In situ infrared spectroscopy revealed that Pt1Pd1-N NFs/CP ensured the complete oxidation of methanol following a CO-free path. The investigation of the electronic and coordination structure demonstrated that the Pt–Pd adjacent sites with a zero valence are the highly active center for MOR, and the synergistic effect between Pt and Pd greatly improved the MOR electrocatalytic performance. This work offers an effective strategy to precisely control the number and structure of decorating species for constructing alloy nanocatalysts to enhance the electroactivity toward MOR.

Abstract 3450: Discovery and preclinical study of novel BTK degrader HZ-Q1070

Abstract Introduction: Bruton's tyrosine kinase (BTK) is a clinical validated target for B cell lymphoma and autoimmune diseases. However, acquired resistance, which is the result of BTK C481S mutation, has been observed in patients. So reversible BTK inhibitors are developed to overcome acquired resistance of covalent BTK inhibitors. In order to achieve adequate efficacy, reversible BTK inhibitors require much higher exposure which may lead to higher risk of adverse effect. Proteolysis-targeting chimera (PROTAC) is a novel drug discovery strategy and achieve sustained target degradation though a catalytic mechanism of action. Comparing with traditional small molecule inhibitor, PROTAC has shown great advantages in overcoming acquired resistance, since potent and sustained active site occupation is no longer required. Here, we have identified a novel BTK-PROTAC HZ-Q1070 based on our DaTProD® platform, which is set up to promote the druggability research of PROTAC. After a series of evaluations, HZ-Q1070 has been validated as a promising pre-clinical candidate for further clinical development. Results: 1. HZ-Q1070 can effectively degrade BTK in cancer cell lines with DC50 < 0.05 nM. In vitro cancer cell growth inhibition assay, it completely suppressed the cell proliferation of a panel of lymphoma cell lines with IC50 < 0.05 nM, such as Mino, OCI-ly10 and TMD8. 2. At the same time, HZ-Q1070 catalyzes the mutated BTK degradation (C481S/C481Y/C481F/T474M) and potently inhibits growth of BTK inhibitor-resistant tumor cell lines. 3. In proteomic analysis assay, HZ-Q1070 can selectively degrade BTK. 4. HZ-Q1070 has been engineered to avoid Aiolos and Ikaros degradation and therefore does not show IMiD activity. 5. Mechanistic investigation of indicates that HZ-Q1070 can function through the ubiquitin-proteasome system (UPS). 6. In the PK/PD experiments, HZ-Q1070 shows excellent pharmacokinetic properties and BTK degradation activity in vivo. 7. HZ-Q1070 demonstrates robust tumor growth inhibition in TMD8 and Mino xenograft mouse model. Doses as low as 3 mg/kg demonstrates a significant inhibitory effect. Conclusion: In summary, HZ-Q1070 is a potent and highly selective BTK degrader against both BTK-WT and multiple BTK inhibitors-resistant mutations. In vivo, HZ-Q1070 exhibits excellent pharmacokinetic properties, BTK degradation activity and robust tumor growth inhibition in TMD8 and Mino mouse xenograft tumor model. These findings support further clinical development of HZ-Q1070 for the treatment of B cell malignancies. Citation Format: Xingguo Liu, Yubo Zhou, Yizhe Wu, Xiaomin Luo, Jiangfeng Xie, Xinxin Jin, Jia Li, Xinglu Zhou. Discovery and preclinical study of novel BTK degrader HZ-Q1070 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3450.

Oxidation State Engineering in Octahedral Ni by Anchored Sulfate to Boost Intrinsic Oxygen Evolution Activity

Promoting the electron occupancy of active sites to unity is an effective method to enhance the oxygen evolution reaction (OER) performance of spinel oxides, but it remains a great challenge. Here, an in situ approach is developed to modify the valence state of octahedral Ni cations in NiFe2O4 inverse spinel via surface sulfates (SO42-). Different from previous studies, SO42- is directly anchored on the spinel surface instead of forming from uncontrolled conversion or surface reconstruction. Experiment and theoretical calculations reveal the precise adsorption sites and spatial arrangement for SO42- species. As a main promoting factor, surface SO42- effectively converts the crystal field stable Ni state (t2g6eg2) to the near-unity eg electron state (t2g6eg1). Moreover, the inevitable oxygen vacancies (Vo) further optimize the energy barrier of the potential-determining step (from OH* to O*). This co-modification strategy enhances turnover frequency-based electrocatalytic activity about two orders higher than the control sample without surface sulfates. This work may provide insight into the OER activity enhancement mechanism by the oxyanion groups.

Kinetic Study of the Influence of Humic Acids on the Oxidation of As(III) by Acid Birnessite

Dissolved arsenic (As) in natural environments is controlled by sorption onto metal oxide surfaces; its speciation is principally influenced by biogenic manganese oxides and natural organic matter (NOM). Manganese (III/IV) oxides are strong oxidants that are ubiquitous in soils and sediments, and humic acids (HA) are typical substances found in the dissolved fraction of NOM. However, the mechanism of As(III) oxidation by MnO2 in the presence of NOM remains poorly understood. Here, we investigate how HA impact the oxidation of As(III) by a synthetic manganese oxide, i.e., acid birnessite (MnO2). We find that the reaction kinetics of As with HA and MnO2 are controlled by the formation of surface complexes. The main observed effect is a decrease of the overall oxidation rate in the presence of HA. In addition, pre-exposure of MnO2 to HA for 24 h further decreases the reaction rate, which is attributed to the occupation of MnO2 surface active sites, thus causing surface passivation. Our results demonstrate that HA influence the reaction mechanism of As(III) oxidation by MnO2 via sorption onto active surface sites and the formation of aqueous complexes.

Dynamic Ir(III) Photosensors for the Major Human Drug-Metabolizing Enzyme Cytochrome P450 3A4.

Probing the activity of cytochrome P450 3A4 (CYP3A4) is critical for monitoring the metabolism of pharmaceuticals and identifying drug-drug interactions. A library of Ir(III) probes that detect occupancy of the CYP3A4 active site were synthesized and characterized. These probes show selectivity for CYP3A4 inhibition, low cellular toxicity, Kd values as low as 9 nM, and are highly emissive with lifetimes up to 3.8 μs in cell growth media under aerobic conditions. These long emission lifetimes allow for time-resolved gating to distinguish probe from background autofluorescence from growth media and live cells. X-ray crystallographic analysis revealed structure-activity relationships and the preference or indifference of CYP3A4 toward resolved stereoisomers. Ir(III)-based probes show emission quenching upon CYP3A4 binding, then emission increases following displacement with CYP3A4 inhibitors or substrates. Importantly, the lead probes inhibit the activity of CYP3A4 at concentrations as low as 300 nM in CYP3A4-overexpressing HepG2 cells that accurately mimic human hepatic drug metabolism. Thus, the Ir(III)-based agents show promise as novel chemical tools for monitoring CYP3A4 active site occupancy in a high-throughput manner to gain insight into drug metabolism and drug-drug interactions.

Electrochemical degradation of PFOA and its common alternatives: Assessment of key parameters, roles of active species, and transformation pathway

This study investigates an electrochemical approach for the treatment of water polluted with per- and poly-fluoroalkyl substances (PFAS), looking at the impact of different variables, contributions from generated radicals, and degradability of different structures of PFAS. Results obtained from a central composite design (CCD) showed the importance of mass transfer, related to the stirring speed, and the amount of charge passed through the electrodes, related to the current density on decomposition rate of PFOA. The CCD informed optimized operating conditions which we then used to study the impact of solution conditions. Acidic condition, high temperature, and low initial concentration of PFOA accelerated the degradation kinetic, while DO had a negligible effect. The impact of electrolyte concentration depended on the initial concentration of PFOA. At low initial PFOA dosage (0.2 mg L−1), the rate constant increased considerably from 0.079 ± 0.001 to 0.259 ± 0.019 min−1 when sulfate increased from 0.1% to 10%, likely due to the production of SO4•–. However, at higher initial PFOA dosage (20 mg L−1), the rate constant decreased slightly from 0.019 ± 0.001 to 0.015 ± 0.000 min−1, possibly due to the occupation of active anode sites by excess amount of sulfate. SO4•– and •OH played important roles in decomposition and defluorination of PFOA, respectively. PFOA oxidation was initiated by one electron transfer to the anode or SO4•–, undergoing Kolbe decarboxylation where yielded perfluoroalkyl radical followed three reaction pathways with •OH, O2 and/or H2O. PFAS electrooxidation depended on the chemical structures where the decomposition rate constants (min−1) were in the order of 6:2 FTCA (0.031) > PFOA (0.019) > GenX (0.013) > PFBA (0.008). PFBA with a shorter chain length and GenX with –CF3 branching had slower decomposition than PFOA. While presence of C–H bonds makes 6:2 FTCA susceptible to the attack of •OH accelerating its decomposition kinetic. Conducting experiments in mixed solution of all studied PFAS and in natural water showed that the co-presence of PFAS and other water constituents (organic and inorganic matters) had adverse effects on PFAS decomposition efficiency.

Tentative exploration on water-promoted catalytic ozonation of Cl-VOCs and feasibility of application in complex flue gas over monolithic cobalt catalyst

It is still challenge to avoid Cl poisoning and achieve efficient elimination of Cl-VOCs at low temperature. This paper tentatively explored water-promoted catalytic ozonation of Cl-VOCs and feasibility of application in complex flue gas over monolithic cobalt catalyst. O 3 decomposition and Cl-VOCs ozonation occur simultaneously but the active radicals and intermediates from O 3 decomposition and Cl-VOCs ozonation have competitive effects on oxygen vacancies. Most interestingly, presence of water vapor and NO, as well as lowering temperature to 50 o C further promote catalytic ozonation of Cl-VOCs. Moisture vapor facilitates desorption of surficial Cl species and deep oxidation by washing effect and provision of additional H source to attain higher conversion and less byproducts. Especially, 1 vol.% water vapor attains ~10% elevation in CH 2 Cl 2 conversion and almost 10%~25% improvement in mineralization rate. NO ozonation generates NO 3 related radicals with strong oxidability to enhance Cl-VOCs conversion and inhibit polychlorinated byproducts formation. Lower temperature promotes adsorption of the above-mentioned active radicals and intermediates to prolong the contact time, thus attaining higher conversion, ca. 100% conversion with O 3 /CH 2 Cl 2 of 12.5 at 50 o C. SO 2 and Ca cause severe deactivation on catalytic ozonation that requires higher O 3 input, which should be attributed to the occupation of active sites and attenuation of acidity. Above all, this paper reports an effective and practical approach for Cl-VOCs elimination in flue gas with potential to simultaneous remove NO. • The monolithic catalyst is firstly used for catalytic ozonation system. • CoO x @Ni attains 90% DCM conversion with O 3 /DCM=6.0 under humid condition at 120 o C. • Water vapor enhances the performance of Cl-VOCs catalytic ozonation over CoO x @Ni. • Simultaneous removal of NO and Cl-VOCs can be achieved during catalytic ozonation.

The highly efficient simultaneous removal of Pb2+ and methylene blue induced by the release of endogenous active sites of montmorillonite

The inherent periodic structure of montmorillonite limits the adsorption capacity of its endogenous active units such as Si-O tetrahedron and Al-O octahedron for pollutants. The high-intensity ultrasound method was used to release these active units and the layer-by-layer assembly was adopted to prepare carbon@chitosan@montmorillointe microsphere adsorbent (C@CS@Mt) to give full play to the adsorption capacity of montmorillonite. The montmorillonite nanosheet exhibited good hole-making ability, resulting in high surface area, pore volume and pore diameter of microspheres. Benefitting from the release of active sites in Si-O tetrahedron and Al-O octahedron of montmorillonite nanosheets, the adsorption capacity of C@CS@Mt was significantly improved. The maximum adsorption capacities of Pb2+ and methylene blue (MB)reached 884.19 mg·g-1 and 326.21 mg·g-1, respectively. The simultaneous adsorption experiments indicated that the occupation of active sites by Pb2+ caused the observeddecrease of MB adsorption capacity. The theoretical calculations indicated that Pb was preferentially adsorbed by active adsorption units due to strong electron donating ability in comparison to MB. As an active unit, Si-O tetrahedron exhibited stronger adsorption capacity for cationic dyes than Al-O octahedron due to both the large electronegativity and lower adsorption binding energy.

Ir(III)-Based Agents for Monitoring the Cytochrome P450 3A4 Active Site Occupancy.

Cytochromes P450 (CYPs) are a superfamily of enzymes responsible for biosynthesis and drug metabolism. Monitoring the activity of CYP3A4, the major human drug-metabolizing enzyme, is vital for assessing the metabolism of pharmaceuticals and identifying harmful drug-drug interactions. Existing probes for CYP3A4 are irreversible turn-on substrates that monitor activity at specific time points in end-point assays. To provide a more dynamic approach, we designed, synthesized, and characterized emissive Ir(III) and Ru(II) complexes that allow monitoring of the CYP3A4 active-site occupancy in real time. In the bound state, probe emission is quenched by the active-site heme. Upon displacement from the active site by CYP3A4-specific inhibitors or substrates, these probes show high emission turn-on. Direct probe binding to the CYP3A4 active site was confirmed by X-ray crystallography. The lead Ir(III)-based probe has nanomolar Kd and high selectivity for CYP3A4, efficient cellular uptake, and low toxicity in CYP3A4-overexpressing HepG2 cells.

Ultrahigh Stable Methanol Oxidation Enabled by a High Hydroxyl Concentration on Pt Clusters/MXene Interfaces.

Anchoring platinum catalysts on appropriate supports, e.g., MXenes, is a feasible pathway to achieve a desirable anode for direct methanol fuel cells. The authentic performance of Pt is often hindered by the occupancy and poisoning of active sites, weak interaction between Pt and supports, and the dissolution of Pt. Herein, we construct three-dimensional (3D) crumpled Ti3C2Tx MXene balls with abundant Ti vacancies for Pt confinement via a spray-drying process. The as-prepared Pt clusters/Ti3C2Tx (Ptc/Ti3C2Tx) show enhanced electrocatalytic methanol oxidation reaction (MOR) activity, including a relatively low overpotential, high tolerance to CO poisoning, and ultrahigh stability. Specifically, it achieves a high mass activity of up to 7.32 A mgPt-1, which is the highest value reported to date in Pt-based electrocatalysts, and 42% of the current density is retained on Ptc/Ti3C2Tx even after the 3000 min operative time. In situ spectroscopy and theoretical calculations reveal that an electric field-induced repulsion on the Ptc/Ti3C2Tx interface accelerates the combination of OH- and CO adsorption intermediates (COads) in kinetics and thermodynamics. Besides, this Ptc/Ti3C2Tx also efficiently electrocatalyze ethanol, ethylene glycol, and glycerol oxidation reactions with comparable activity and stability to commercial Pt/C.

Non-bonding electronic reconfiguration by surface engineering in shandite A3M2S2 (A=Fe, Co; M=In, Sn) for hydrogen evolution reaction

Searching for intriguing electronic structures at catalyst surface have attracted much attentions due to the potential applications in hydrogen evolution reaction (HER). Herein, the A3M2S2 (A = Fe, Co; M = In, Sn) materials with shandite phase are proposed to design surficial electronic structure due to the existence of an ideal kagome net, in which the ordered occupation of half of A-sites leads to a half-antiperowskites atomic configuration A3/2MS. Thanks for this particular crystal symmetry, the electronic reconfiguration induced by spontaneous super-exchange interaction can lead to an excellent HER activity when the surface is covered by non-bonding M (In, Sn) and S atoms. This orbital hybridization is different from the direct bonding interaction from In–S bonds or Sn–S bonds. Comprehensive density functional theory (DFT) calculations disclose this indirect orbital hybridization not only regulates the electronic occupation of active sites but also can affect their bonding interaction with reactants. These findings suggest a new strategy into enhancing reactive activity.

Extruded monolith MnOx-CeO2-TiO2 catalyst for NH3-SCR of low temperature flue gas from an industry boiler: Deactivation and recovery

The selective catalytic reduction (SCR) of NOx with NH3 (NH3-SCR) technology has been widely applied for reducing NOx emissions from stationary and mobile sources. In this work, the extruded monolith MnOx-CeO2-TiO2 catalyst was installed in a cement kiln for NH3-SCR of NOx, where the flue gas temperature was 110–140 ℃. It is found that the monolith catalyst is severely deactivated after operating for about 200 h with almost no NOx conversion at 160 ℃ under GHSV of 50000 h−1, while the fresh monolith catalyst remains 60% NOx conversion. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), temperature-programmed desorption of SO2 (SO2-TPD) and thermogravimetric-differential thermal analysis (TG-DTG) experiments reveal that both MnOx and CeO2 oxides in monolith are severely sulfated to manganese sulfate and cerium sulfate, and the external monolith walls are covered by massive ceria sulfate and little ammonium nitrate. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis demonstrates that the formation of nitrates at low temperatures is inhibited due to the occupation of active sites in MnOx-CeO2-TiO2 by sulfates, resulting in the decrease of low temperature activity. After washing with water, the activity of deactivated monolith catalyst can be partially recovered, together with significant loss of manganese and cerium from monolith.