Coordination Desymmetrization of Copper Single-Atom Catalyst for Efficient Nitrate Reduction.

Coordination engineering strategy for optimizing the catalytic performance of single-atom catalysts (SACs) has been rapidly developed over the last decade. However, previous reports on copper SACs for nitrate reduction reactions (NO3RR) have mostly focused on symmetric coordination configurations such as Cu-N4 and Cu-N3. In addition, the mechanism in terms of the regulation of coordination environment and catalytic properties of SACs has not been well demonstrated. Herein, we disrupted the local symmetric structure of copper atoms by introducing unsaturated heteroatomic coordination of Cu-O and Cu-N to achieve the coordination desymmetrization of Cu-N1O2 SACs. The Cu-N1O2 SACs exhibit an efficient nitrate-to-ammonia conversion with a high FE of ~96.5 % and a yield rate of 3120 µg NH3 h-1 cm-2 at -0.60 V vs RHE. As indicated by in situ Raman spectra, the catalysts facilitate the accumulation of NO3 - and the selective adsorption of *NO2, which were further confirmed by the theoretical study of surface dipole moment and orbital hybridization. Our work illustrated the correlation between the coordination desymmetrization and the catalytic performance of copper SACs for NO3RR.

Low-loss chalcogenide microstructured optical fibers prepared by eliminating interfaces defects.

The loss of chalcogenide microstructured optical fibers (ChG-MOFs) is generally higher than that of step fibers, mainly due to the immature fiber preform preparation method and strong waveguide defect scattering. Chemical polishing is used to polish mechanically drilled preforms to prepare ChG-MOFs with low defect scattering. Firstly, the scattering loss caused by the defective layer of ChG-MOFs is studied theoretically and experimentally. Then, a single-mode photonic crystal fiber (PCF) was prepared to verify the effect of chemical polishing on reducing fiber loss. The experimental results show that the PCF average loss is reduced from more than 8 dB/m to less than 2 dB/m, and the minimum loss reaches 0.8 dB/m @ 2.7 µm. At the same time, the bending strength of the PCF after chemical polishing is also significantly improved.

Chalcogenide GRIN glasses with high refractive index and large refractive index difference for LWIR imaging.

Gradient refractive index (GRIN) materials utilize an internally tailored refractive index in combination with the designed curvature of the optical element surface, providing the optical designer with additional freedom for correcting chromatic and spherical aberrations. In this paper, new GRIN materials suitable for the second (3-5 µm) and third (8-12 µm) atmospheric windows were successfully developed by the thermal diffusion method based on Ge20As20Se60-xTex series high refractive index glasses, where the maximum refractive index difference (Δn) at 4 µm and 10.6 µm were 0.281 and 0.277, respectively. The diffusion characteristics and refractive index distribution of the GRIN glass were analyzed by Raman characterization. Furthermore, the performance of GRIN singlet and homogeneous singlet in the LWIR band (8 µm, 10.6 µm (primary wavelength), 12 µm) was compared, and the results showed that the GRIN singlet had better chromatic aberration correction and unique dispersion characteristics.

Large mode-area all-solid anti-resonant fiber based on chalcogenide glass for mid-infrared transmission.

A large mode-area chalcogenide all-solid anti-resonant fiber has been designed and successfully prepared for the first time. The numerical results show that the high-order mode extinction ratio of the designed fiber can reach 6000, and the maximum mode-area is 1500 um2. The fiber possesses a calculated low bending loss of less than 10-2 dB/m as the bending radius is larger than 15 cm. In addition, there is a low normal dispersion of -3 ps/nm/km at 5 µm, which is beneficial for the transmission of high power mid-infrared laser. Finally, a completely structured all-solid fiber was prepared by the precision drilling and two-stage rod-in-tube methods. The fabricated fibers transmit in the mid-infrared spectral range from 4.5 to 7.5 µm with the lowest loss of 7 dB/m @ 4.8 µm. Modeling suggests that the theoretical loss of the optimized structure is consistent with that of the prepared structure in the long wavelength band.

Green synthesis of DOX-loaded hollow MIL-100 (Fe) nanoparticles for anticancer treatment by targeting mitochondria.

Fe-based metal-organic frameworks (MOFs) are promising drug delivery materials due to their large surface area, high stability, and biocompatibility. However, their drug loading capacity is constrained by their small pore size, and a further improvement in their drug capacity is needed. In this work, we report an effective and green structural modification strategy to improve drug loading capacity for Fe-based MOFs. Our strategy is to grow MIL-100 (Fe) on carboxylate-terminated polystyrene (PS-COOH) via a sustainable route, which creates a large inner cavity as well as exposure to more functional groups that benefit drug loading capacity. We employ the scanning electron microscope and transmission electron microscope to confirm the hollow structure of MIL-100 (Fe). Up to 30% of drug loading capacity has been demonstrated in our study. We also conduct cell viability tests to investigate its therapeutic effects on breast cancer cells (MDA-MB-231). Confocal laser scanning microscopy imaging confirms cellular uptake and mitochondrial targeting function of doxorubicin-loaded H-M (DOX@H-M) nanoparticles. JC-1 staining of cancer cells reveals a significant change in the mitochondrial membrane potential, indicating the mitochondrial dysfunction and apoptosis of tumor cells. Our study paves the way for the facile synthesis of hollow structural MOFs and demonstrates the potential of applying Fe-based MOFs in breast cancer treatment.

Bimetallic-MOF-Derived Amorphous Zinc/Cobalt-Iron-Based Hollow Nanowall Arrays via Ion Exchange for Highly Efficient Oxygen Evolution.

Oxygen evolution reaction (OER) is critical for optimizing renewable energy systems, including metal-air batteries and water electrolysis. One major challenge for OER is to develop durable and cost-effective electrocatalysts with high catalytic performance. Herein, a controllable ion-exchange method to synthesize amorphous zinc/cobalt-iron hydroxide-based hollow nanowall arrays (A-Zn/Co-Fe HNAs) derived from bimetallic metal-organic frameworks (MOFs) on carbon cloth is reported. The amorphous characteristic enables the presented materials with more electrocatalytic sites and short diffusion paths for rapid access to the electrolyte, achieving efficient charge transfer for OER. The optimized nanostructure of A-Zn/Co-Fe HNAs via tuning the amount of iron sulfate in the reaction solution delivers a low overpotential of 226 mV to reach a current density of 10 mA cm-2 with a small Tafel slope of 37.81 mV dec-1 while exhibiting high durability at varied current densities over 80 h. The remarkable electrochemical performance can be attributed to the synergistic effect from chemical elements of Zn, Co-Fe, and a robust hollow structure. This simple method of fabricating bimetallic-MOF-derived amorphous Zn/Co-Fe HNAs on carbon cloth can be applied as a practical platform for other OER electrocatalysts.

Chitosan-based hydrogel dressings for diabetic wound healing via promoting M2 macrophage-polarization.

A long-term inflammatory phase of diabetic wounds is the primary cause to prevent their effective healing. Bacterial infection, excess reactive oxygen species (ROS), especially failure of M2-phenotype macrophage polarization can hinder the transition of diabetic wounds from an inflammation phase to a proliferation one. Herein, a chitosan-based hydrogel dressing with the ability of regulating M2 macrophage polarization was reported. The PAAc/CFCS-Vanillin hydrogel dressing was synthesized by one step thermal polymerization of catechol-functionalized chitosan (CFCS), acrylic acid, catechol functional methacryloyl chitosan­silver nanoparticles (CFMC-Ag NPs) and bioactive vanillin. The PAAc/CFCS-Vanillin hydrogel possessed sufficient mechanical strength and excellent adhesion properties, which helped rapidly block bleeding of wounds. Thanks to CFCS, CFMC-Ag NPs and vanillin in the hydrogel, it displayed excellent antibacterial infection in the wounds. Vanillin helped scavenge excess ROS and regulate the levels of inflammatory factors to facilitate the polarization of macrophages into the M2 phenotype. A full-thickness skin defect diabetic wound model showed that the wounds treated by the PAAc/CFCS-Vanillin hydrogel exhibited the smallest wound area, and superior granulation tissue regeneration, remarkable collagen deposition, and angiogenesis were observed in the wound tissue. Therefore, the PAAc/CFCS-Vanillin hydrogel could hold promising potential as a dressing for the treatment of diabetic chronic wounds.

Unraveling Ros Conversion Through Enhanced Enzyme-Like Activity with Copper-Doped Cerium Oxide for Tumor Nanocatalytic Therapy.

Nanozyme catalytic therapy for cancer treatments has become one of the heated topics, and the therapeutic efficacy is highly correlated with their catalytic efficiency. In this work, three copper-doped CeO2 supports with various structures as well as crystal facets are developed to realize dual enzyme-mimic catalytic activities, that is superoxide dismutase (SOD) to reduce superoxide radicals to H2 O2 and peroxidase (POD) to transform H2 O2 to ∙OH. The wire-shaped CeO2 /Cu-W has the richest surface oxygen vacancies, and a low level of oxygen vacancy (Vo) formation energy, which allows for the elimination of intracellular reactive oxygen spieces (ROS) and continuous transformation to ∙OH with cascade reaction. Moreover, the wire-shaped CeO2 /Cu-W displays the highest toxic ∙OH production capacity in an acidic intracellular environment, inducing breast cancer cell death and pro-apoptotic autophagy. Therefore, wire-shaped CeO2 /Cu nanoparticles as an artificial enzyme system can have great potential in the intervention of intracellular ROS in cancer cells, achieving efficacious nanocatalytic therapy.

Tailoring the catalytic activity and selectivity on CO2 to C1 products by the synergistic effect of reactive molecules: A DFT study.

The conversion of CO2 to CO is one of the crucial pathways in the carbon dioxide reduction reaction (CO2RR). Iron and nitrogen co-doped carbon matrix (FeN4) is a promising catalyst for converting CO2to CO with excellent activity and selectivity. However, the reactive mechanism of CO2RR on the FeN4 catalyst is not fully unveiled. For example, it is still evasive that the obtained C1 product is methanol and/or methane instead of CO in some cases. Herein, DFT calculation is conducted to unravel the effect from both solvent molecules and intermediates as axial groups on the selectivity of C1 products in CO2RR using FeN4 catalyts. Calculation results demonstrate that the FeN4(H), FeN4(OH), FeN4(COOH), and FeN4(CO) configurations are not only beneficial to the removal of CO, but also effectively suppress the hydrogen evolution reaction, whereas the FeN4, FeN4(CO2) and FeN4(H2O) configurations are inclined to produce CH3OH and/or CH4. The mechanism studied in this work provides an inspiration of optimizing the selectivity of C1 products in CO2RR from the perspective of regulating solvent molecules and intermediates as axial groups on FeN4.

Intermediates Regulation via Electron-Deficient Cu Sites for Selective Nitrate-to-Ammonia Electroreduction.

Ammonia (NH3 ), known as one of the fundamental raw materials for manufacturing commodities such as chemical fertilizers, dyes, ammunitions, pharmaceuticals, and textiles, exhibits a high hydrogen storage capacity of ≈17.75%. Electrochemical nitrate reduction (NO3 RR) to valuable ammonia at ambient conditions is a promising strategy to facilitate the artificial nitrogen cycle. Herein, copper-doped cobalt selenide nanosheets with selenium vacancies are reported as a robust and highly efficient electrocatalyst for the reduction of nitrate to ammonia, exhibiting a maximum Faradaic efficiency of ≈93.5% and an ammonia yield rate of 2360 µg h-1 cm-2 at -0.60 V versus reversible hydrogen electrode. The in situ spectroscopical and theoretical study demonstrates that the incorporation of Cu dopants and Se vacancies into cobalt selenide efficiently enhances the electron transfer from Cu to Co atoms via the bridging Se atoms, forming the electron-deficient structure at Cu sites to accelerate NO3 - dissociation and stabilize the *NO2 intermediates, eventually achieving selective catalysis in the entire NO3 RR process to produce ammonia efficiently.

Molybdenum-iron-cobalt oxyhydroxide with rich oxygen vacancies for the oxygen evolution reaction.

The sluggish kinetics of the oxygen evolution reaction (OER) restrains the development of water splitting technologies and the efficiency of producing sustainable resources. To this end, the introduction of iron and molybdenum in catalytic systems has been employed as a crucial strategy for the enhancement of catalytic activity toward the oxygen evolution reaction (OER), but the relationship between catalyst components and catalytic performance is still evasive. In this study, by doping iron and molybdenum into cobalt hydroxide via a cation-exchange method, rich oxygen vacancies and active metal centers are introduced to the trimetallic oxyhydroxide, endowing the catalyst with a low overpotential of 223 mV at 10 mA cm-2, a low Tafel slope of 43.6 mV dec-1, and a long stable operation time (>50 h) in alkaline media, comparable to the current best OER catalyst. Moreover, it is demonstrated that the doping of iron favors the generation of oxygen vacancies. It is also found in this work that using a certain amount (5 mg) of iron dopant can alter the electronic structure of the catalyst by tuning the electronic density around the metal ions, thus optimizing the binding energy of intermediates. The present work unveils the doping effect of iron and molybdenum on the construction of trimetallic oxyhydroxide catalysts, and sheds light on the relationship between the catalyst components and catalytic performance of the OER.

Unveiling the Accelerated Water Electrolysis Kinetics of Heterostructural Iron-Cobalt-Nickel Sulfides by Probing into Crystalline/Amorphous Interfaces in Stepwise Catalytic Reactions.

Amorphization and crystalline grain boundary engineering are adopted separately in improving the catalytic kinetics for water electrolysis. Yet, the synergistic effect and advance in the cooperated form of crystalline/amorphous interfaces (CAI) have rarely been elucidated insightfully. Herein, a trimetallic FeCo(NiS2 )4 catalyst with numerous CAI (FeCo(NiS2 )4 -C/A) is presented, which shows highly efficient catalytic activity toward both hydrogen and oxygen evolution reactions (HER and OER). Density functional theory (DFT) studies reveal that CAI plays a significant role in accelerating water electrolysis kinetics, in which Co atoms on the CAI of FeCo(NiS2 )4 -C/A catalyst exhibit the optimal binding energy of 0.002 eV for H atoms in HER while it also has the lowest reaction barrier of 1.40 eV for the key step of OER. H2 O molecules are inclined to be absorbed on the interfacial Ni atoms based on DFT calculations. As a result, the heterostructural CAI-containing catalyst shows a low overpotential of 82 and 230 mV for HER and OER, respectively. As a bifunctional catalyst, it delivers a current density of 10 mA cm-2 at a low cell voltage of 1.51 V, which enables it a noble candidate as metal-based catalysts for water splitting. This work explores the role of CAI in accelerating the HER and OER kinetics for water electrolysis, which sheds light on the development of efficient, stable, and economical water electrolysis systems by facile interface-engineering implantations.

Characterization of a novel and selective CB1 antagonist as a radioligand for receptor occupancy studies.

Obesity remains a significant public health issue leading to Type II diabetes and cardiovascular disease. CB1 antagonists have been shown to suppress appetite and reduce body weight in animal models as well as in humans. Evaluation of pre-clinical CB1 antagonists to establish relationships between in vitro affinity and in vivo efficacy parameters are enhanced by ex vivo receptor occupancy data. Synthesis and biological evaluation of a novel and highly selective radiolabeled CB1 antagonist is described. The radioligand was used to conduct ex vivo receptor occupancy studies.

Precise tuning of heteroatom positions in polycyclic aromatic hydrocarbons for electrocatalytic nitrogen fixation.

The electrochemical dinitrogen reduction represents an attractive approach of converting N2 and water into ammonia, while the rational design of catalytic active centers remains challenging. Investigating model molecular catalysts with well-tuned catalytic sites should help to develop a clear structure-activity relationship for electrochemical N2 reduction. Herein, we designed several polycyclic aromatic hydrocarbon (PAH) molecules with well-defined positions of boron and nitrogen atoms. Theoretical calculations revealed that the boron atoms possess high local positive charge densities as Lewis acid sites, which are beneficial for N2 adsorption and activation, thus serving as major catalytic active sites for N2 electrochemical reduction. Furthermore, the close vicinity of two boron atoms can further enhance the local positive density and subsequent catalytic activity. Using the PAH molecule with two boron atoms separated by two carbon atoms (B-2C-B), a high NH3 production rate of 34.58 µg·h-1·cm-2 and a corresponding Faradaic efficiency (5.86%) were achieved at -0.7 V versus reversible hydrogen electrode, substantially exceeding the other PAHs with single boron or nitrogen-containing molecular structures.

Pushing the activity of CO2 electroreduction by system engineering.

As a promising technology that may solve global environmental challenges and enable intermittent renewable energy storage as well as zero-carbon-emission energy cycling, the carbon dioxide reduction reaction has been extensively studied in the past several years. Beyond the fruitful progresses and innovations in catalysts, the system engineering-based research on the full carbon dioxide reduction reaction is urgently needed toward the industrial application. In this review, we summarize and discuss recent works on the innovations in the reactor architectures and optimizations based on system engineering in carbon dioxide reduction reaction. Some challenges and future trends in this field are further discussed, especially on the system engineering factors.

Electrochemical N2 fixation by Cu-modified iron oxide dendrites.

The electrochemical nitrogen reduction reaction (NRR) under mild conditions is significantly challenging, due to the extremely high stability of dinitrogen (N2) molecules. The NRR pathway also confronts the competitive water reduction reaction that takes places universally in an aqueous solution. Herein, a Fe2O3/Cu catalyst is demonstrated as an efficient NRR electrocatalyst. The electronic interactions elevate the d-state electron center, enabling strong back-bonding for N2 molecules. The altering of d-electron distribution promotes the adsorption of N2, leading to a high catalytic activity. As a result, the Fe2O3/Cu catalyst exhibits an outstanding ammonia production rate of 15.66 µg·h-1·mgcat.-1 at -0.1 V versus reversible hydrogen electrode (RHE), a Faradaic efficiency of 24.4%, and a good electrochemical stability.

Mesoporous tin oxide for electrocatalytic CO2 reduction.

The increasing accumulation of CO2 in the atmosphere has been leading to serious environmental problems. Electrochemical reduction of CO2 is a potential means of carbon recycling for energy storage and environmental sustainability. However, it is limited by the lack of highly active and selective electrocatalysts. Here we demonstrate the development of mesoporous tin oxide (SnO2) for electrocatalytic CO2 reduction, which facilitates the adsorption and electrochemical reduction of CO2 inside mesopores. The highly-ordered and uniform pore sizes of the mesoporous SnO2 electrocatalyst favor the enhancement of formation of carbon monoxide (CO) and formate during the electrochemical reduction. The combined faradaic efficiencies of CO and formate reach a peak value of ∼80% at a current density of 5 mA cm-2 at -0.8 V vs. reversible hydrogen electrode. This work suggests attractive development of mesoporous electrocatalysts with a variety of pore size and structures for efficient energy conversion and electrochemical CO2 reduction.

Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists.

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics.

In a previous report we demonstrated that merging together key structural elements present in an AT(1) receptor antagonist (1, irbesartan) with key structural elements in a biphenylsulfonamide ET(A) receptor antagonist (2) followed by additional optimization provided compound 3 as a dual-action receptor antagonist (DARA), which potently blocked both AT(1) and ET(A) receptors. Described herein are our efforts directed toward improving both the pharmacokinetic profile as well as the AT(1) and ET(A) receptor potency of 3. Our efforts centered on modifying the 2'-side chain of 3 and examining the isoxazolylsulfonamide moiety in 3. This effort resulted in the discovery of 7 as a highly potent second-generation DARA. Compound 7 also showed substantially improved pharmacokinetic properties compared to 3. In rats, DARA 7 reduced blood pressure elevations caused by intravenous infusion of Ang II or big ET-1 to a greater extent and with longer duration than DARA 3 or AT(1) or ET(A) receptor antagonists alone. Compound 7 clearly demonstrated superiority over irbesartan (an AT(1) receptor antagonist) in the normal SHR model of hypertension in a dose-dependent manner, demonstrating the synergy of AT(1) and ET(A) receptor blockade in a single molecule.

Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally active ET(A) selective antagonist.

We have previously disclosed the selective ET(A) receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS-193884) as a clinical development candidate. Additional SAR studies at the 2'-position of 1 led to the identification of several analogues with improved binding affinity as well as selectivity for the ET(A) receptor. Following the discovery that a 3-amino-isoxazole group displays significantly improved metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole group was combined with the optimal 2'-substituent leading to 16a (BMS-207940). Compound 16a is an extremely potent (ET(A) K(i) = 10 pM) and selective (80,000-fold for ET(A) vs ET(B)) antagonist. It is also 150-fold more potent and >6-fold more selective than 1. The bioavailability of 16a was 100% in rats and the systemic clearance and volume of distribution are higher than that of 1. In rats, intravenous 16a blocks big ET pressor responses with 30-fold greater potency than 1. After oral dosing at 3 micromol/kg, 16a displays enhanced duration relative to 1.