Search

One-step synthesis of 2-propylheptanol (2-PH) from n-pentanal via a reaction integration of n-pentanal self-condensation and successive hydrogenation is of great significance for it can simplify process flow and reduce energy consumption. The key to promotion of 2-PH selectivity is to enhance the competitiveness of n-pentanal self-condensation with respect to its direct hydrogenation. For this purpose, a core-shell structured Ni/SiO2@TiO2 catalyst was designed and prepared. With the precise architecture of this core-shell structured catalyst, n-pentanal can be firstly in contact with TiO2 to 2-propyl-2-heptenal (2-PHEA) while the direct hydrogenation to n-pentanol can be effectively inhibited, and then 2-PHEA diffuses into the core of Ni/SiO2 and is hydrogenated to 2-PH. The spatial threshold of the core-shell catalyst significantly enhanced its catalytic performance; a 2-PH selectivity of 77.9% was reached with a 100% n-pentanal conversion. The 2-PH selectivity is much higher than that obtained by employing Ni/TiO2 catalyst. Furthermore, the reaction kinetics of one-step synthesis of 2-PH from n-pentanal catalyzed by Ni/SiO2@TiO2 was studied and its kinetic model was established which is useful for reactor design and scale-up.

Both sulfur and fluorine play important roles in organic synthesis, the life science, and materials science. The direct incorporation of these elements into organic scaffolds with precise control of the oxidation states of sulfur moieties is of great significance. Herein, we report the highly selective electrochemical vicinal fluorosulfenylation and fluorosulfoxidation reactions of alkenes, which were enabled by the unique ability of electrochemistry to dial in the potentials on demand. Preliminary mechanistic investigations revealed that the fluorosulfenylation reaction proceeded through a radical-polar crossover mechanism involving a key episulfonium ion intermediate. Subsequent electrochemical oxidation of fluorosulfides to fluorosulfoxides were readily achieved under a higher applied potential with the adventitious H2O in the reaction mixture.

Monoamine oxidase A (MAO-A) is a prominent myocardial source of reactive oxygen species (ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAO-A activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart failure. However, so far, there is no report on the fluorescent diagnosis of heart failure by a specific probe for MAO-A. In this work, two far-red emissive fluorescent turn-on probes (KXS-M1 and KXS-M2) for the highly selective and sensitive detection of MAO-A were fabricated. Both probes exhibit good response to MAO-A, one of which, KXS-M2, performs better than the other one in terms of a fluorescence increment and sensitivity. Using the pioneering probe KXS-M2, specific fluorescence imaging of MAO-A in glucose-deprived H9c2 cardiac cells, zebrafish and isoprenaline-induced failing heart tissues was achieved, proving that KXS-M2 can serve as a powerful tool for the diagnosis and treatment of heart failure.

International audience

Selective chemical modulators are ideal tools to study the function of a protein. Yet, the poor ligandability of many proteins has hampered the development of specific chemical probes for numerous protein classes. Tools, such as covalent inhibitors and activity-based protein profiling, have enhanced our understanding of thus-far difficult-to-target proteins and have enabled correct assessment of the selectivity of small-molecule modulators. This also requires deeper knowledge of compound and target site reactivity, evaluation of binding to noncovalent targets and protein turnover. The availability of highly selective chemical probes, the evolution of activity-based probes, and the development of profiling methods will open a new era of drugging the undruggable proteome.

During the last years, the use of biosensors in food analysis has gained considerable interest. These analytical devices provide highly selective, sensitive and cost-effective detection of cells, chemical or biochemical compounds that are relevant for food industry. In special, such sensors can be employed to control and monitoring biotechnological processes for food production and transformation. This review provides an overview on the state-of-the-art of electrochemical biosensors with potential use in food bioprocess technology, focusing on those with potential application in fermentation productions.

Conversion of methane into liquid alcohol such as ethanol at low temperature in a straight, selective and low energy consumption process remains a topic of intense scientific research but a great challenge. In this work, CuFe2O4/CNT composite is successfully synthesized via a facile co-reduction method and used as catalysts to selectively oxidize methane. At a low temperature of 150 °C, methane is directly converted to ethanol in a single process on the as-prepared CuFe2O4/CNT composite with high selectivity. A mechanism is also proposed for the significant methane selective oxidation performance of the CuFe2O4/CNT composite catalysts.

Abstract: Alzheimer’s Disease (AD), a progressive and irreversible neurodegenerative disorder, is the most common form of dementia worldwide. Currently, there is no disease-modifying AD drug, and the development of effective treatments is made even harder by the highly selective nature of the Blood-Brain Barrier (BBB) that allows the passage only of molecules with specific chemical-- physical properties. In this context, nanomedicine and its Nanoparticles (NPs) offer potential solutions to the challenge of AD therapy, in particular, the requirements for i) BBB crossing, ii) multitarget therapy iii) enhancement of pharmacokinetics; and iv) more precise delivery. In addition, the possibility to optimize NP biophysical and biological (i.e. target-specific ligands) properties allows for highly tailored delivery platforms. Preclinical studies have demonstrated that nanotherapeutics provide superior pharmacokinetics and brain uptake than free drugs and, on the other hand, these are also able to mitigate the side-effects of the symptomatic treatments approved by the FDA. Among the plethora of potential AD nanodrugs, multitarget nanotherapeutics are considered the most promising strategy due to their ability to hit simultaneously multiple pathogenic factors, while nano-nutraceuticals are emerging as interesting tools in the treatment/prevention of AD. This review provides a comprehensive overview of nanomedicine in AD therapy, focusing on key optimization of NPs properties, most promising nanotherapeutics in preclinical studies and difficulties that are limiting the efficient translation from bench to bedside.

The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole, cyantraniliprole, etc., targets insect RyRs and can be used to control a wide range of destructive agricultural pests. The diamide insecticides are highly selective against lepidopteran and coleopteran pests with relatively low toxicity for non-target species, such as mammals, fishes, and beneficial insects. However, recently mutations identified on insect RyRs have emerged and caused resistance in several major agricultural pests throughout different continents. This review paper summarizes the recent findings on the structure and function of insect RyRs as insecticide targets. Specifically, we examine the structures of RyRs from target and non-target species, which reveals the molecular basis for insecticide action and selectivity. We also examine the structural and functional changes of RyR caused by the resistance mutations. Finally, we examine the progress in RyR structure-based insecticide design and discuss how this might help the development of a new generation of green insecticides.

Dipicolinate acid (DPA) is an anthrax biomarker. It's serious consequences make it's detection in great need. In this paper, three novel metal-organic frameworks (MOFs) with different coordination modes were synthesized by a simple solvothermal method, which can be used as highly efficient fluorescence sensors for the highly selective and sensitive trace detection of DPA. MOFs 1-3 showed rapid responses to DPA (< 30s), and the limit of detections (LODs) were figured as 1.01×10-6 M-1 (MOF 1), 1.17×10-6 M-1 (MOF 2) and 2.07×10-6 M-1 (MOF 3). DPA detection based on MOFs 1-3 in fetal bovine serum is highly reliable based on high recovery rates (90 % to 115 %). Hence, the three MOF-based sensors can be used in the real-time detection of DPA.

Acyclic carbene–ruthenium catalysts were developed for the ethenolysis. Remarkable catalytic efficiency (turnover numbers of 100 000) and excellent α-olefin selectivity (up to 98%) were exhibited.

Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([11C]-DASB, [123I]-ADAM, and [11C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis–Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis–Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.

Here, the graphene oxide (GO)/SiO2-loaded dual-imprinted membranes (GS-DIMs) were constructed based on the self-polymerization imprinting technique of dopamine, in which a twice polydopamine (PDA)-based imprinting strategy had been successfully developed to obtain the three-dimensional nanocomposite membrane-based separation system. Meanwhile, the pollution-intensive antibiotics of tetracycline (TC) was used as template molecule throughout the GS-DIMs synthesis, and the dopamine molecules were simultaneously used as functional monomer and cross-linking agent during the twice polydopamine (PDA)-based imprinting processes. Therefore, dual-TC-imprinted sites had been prepared based on the as-designed dual imprinting processes, the as-prepared GS-DIMs-based separation system with dual-TC-imprinted structures could not only allow for the largely enhanced rebinding result of 65.61 mg/g and faster adsorption equilibrium rate within 20 min, but also facilitate the permselectivity performance from TC-based complex separation system and mimetic water sample. Importantly, we demonstrated the applications and effects of the dual-imprinted membrane-based separation materials to selective rebinding and separation of TC from complex solution systems and mimetic water samples. The as-obtained permselectivity factors (β) around 4.0 strongly illustrated the efficiently selective separation ability and high-intensitive recognizability of TC than any other non-template molecules based on our GS-DIMs-based separation system. Overall, the as-designed GS-DIMs had great potential for selective separation applications and provided critical comparisons based on the as-achieved excellent rebinding and permselectivity performance, which encompassed innovative GO/SiO2-loaded nanocomposite and PDA-based dual-TC-imprinted system.

The semi-hydrogenation of alkynols to enols is a crucial process in the production of pharmaceuticals, agrochemicals, fragrances, and flavors that involves a complex set of parallel and consecutive isomerization and hydrogenation reactions and proceeds via several key intermediates. In view of the industrial importance of large-scale enol production through alkynol hydrogenation, various noble and non-noble metal (e.g., Ni and Pd)-based catalysts promoting this transformation have been developed. This paper reviews the design of highly selective catalysts for the semi-hydrogenation of alkynols, focusing on the role of additives, second metals, catalyst supports, and reaction conditions and combining catalytic reaction kinetics with theoretical calculations to establish the reaction mechanism and the decisive factors for boosting selectivity. Finally, a strategy for designing highly efficient and selective catalysts based on the characteristics of aqueous-phase alkynol hydrogenation is proposed.

In this article, we propose high-performance colorimetric detection of Hg+2 using silver nanoprisms. The spherical and triangular AgNPs were synthesized using varied concentration of NaBH4. Pristine AgNPs without any further modification were used for the detection of various metal ions including Hg2+, Pb2+, Cl−, Cd2+, Co2+, Cu2+, Ba2+, Pb2+, Cr3+, Cr2O2−7 , Fe2+, Fe3+ etc. AgNPs were not only selective in detecting the ions of Cl− and Hg+2 ions but also highly sensitive. Minimum detection limit was observed to be as low as 10−7 ppm for both Hg+2 and Cl−. Water samples collected from various locations detected for the presence of various heavy metals. Silver nanoprisms owing to their surface plasmon resonance exhibit highly selective tendency towards detection against Hg+2.

Este artigo tem como objetivo identificar as representações sociais de “escola pública” e “professor de escola pública” construídas por universitários matriculados em cursos de alta seletividade da Universidade de Pernambuco (UPE). Resulta de um estudo qualitativo que utilizou como instrumento de coleta a entrevista narrativa. Participaram da pesquisa 11 estudantes universitários, egressos exclusivamente de escola pública, matriculados em cursos de alta seletividade na UPE. As narrativas foram analisadas com o apoio da técnica de análise de conteúdo. Os resultados apontaram que a escola pública está representada como a instituição que fornece formação abrangente, tanto acadêmica quanto cidadã, propicia aprendizagens diversas, orienta e direciona as escolhas profissionais. O “professor de escola pública” é representado como uma figura de referência, alguém que estabelece relações interpessoais de amizade, incentiva e acredita no potencial dos estudantes. Os achados destacam a importância da escola pública para a formação da população e indicam a necessidade de políticas educacionais que favoreçam esse espaço formativo e valorizem do professor.

Selective synthesis of higher oxygenates from syngas is an important but challenging research target, and the present methods for converting syngas into oxygenates suffer from low selectivity and h...

Pd-catalyzed carbonylation, as an efficient synthetic approach for the installation of carbonyl groups in organic compounds, has been one of the most important research fields in the past decade. Although elegant reactions that allow highly selective carbonylations have been developed, straightforward routes with improved reaction activity and broader substrate scope remain long-term challenges for new practical applications. Here, we show a new type of synergistic Cu/Pd-catalyzed carbonylation reaction using alcohols and dioxgen as the carbonyl sources. A broad range of aryl iodides and alcohols are compatible with this protocol. The reaction is concise and practical due to the ready availability of the starting materials and the scalability of the reaction. In addition, the reaction affords lactones and lactams in an intermolecular fashion. Moreover, DFT calculations have been performed to study the detailed mechanisms.

Streptomycin (STR) plays an essential role in bacterial infection treatments. Selectivity and sensitivity of photoelectrochemical (PEC) sensors are the two most important parameters, which can be measured using the photosensitivity of its active material. We prepared a novel PEC sensor to detect STR using Bi/BiVO4/LDH (layered double hydroxides) heterostructures as an active material, which is photoactive in the visible light wavelength range. The simultaneous presence of LDH and Bi/BiVO4 enhanced the material photocurrent response, which was linear to the STR concentrations in the 0.01–500 nmol/L range. The STR detection limit by this sensor was 0.0042 nmol/L. Our novel PEC-based sensing strategy includes using an ultra-sensitive and highly selective sensor for STR detection. Additionally, the two-pot synthesis of Bi/BiVO4/LDH developed in this work is environmentally friendly.

During the utilization of structural and functional advantages of polyoxometalates (POMs) for enhanced applications, a suitable assembly of these clusters in framework materials to act as binding n...

Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets. High-throughput screening (HTS) for multitarget-directed ligands (MTDLs) using approved drugs, and fragment-based drug design has become a regular strategy to achieve an ideal multitarget combination. However, the unexpected presence of pan-assay interference compounds (PAINS) suspects in the development of MTDLs frequently results in nonspecific interactions or other undesirable effects leading to artefacts or false-positive data of biological assays. Publicly available filters can help to identify PAINS suspects; however, these filters cannot comprehensively conclude whether these suspects are “bad” or innocent. Additionally, these in silico approaches may inappropriately label a ligand as PAINS. More than 80% of the initial hits can be identified as PAINS by the filters if appropriate biochemical tests are not used resulting in false positive data that are unacceptable for medicinal chemists in manuscript peer review and future studies. Therefore, extensive offline experiments should be used after online filtering to discriminate “bad” PAINS and avoid incorrect evaluation of good scaffolds. We suggest that the use of “Fair Trial Strategy” to identify interesting molecules in PAINS suspects to provide certain structure‒function insight in MTDL development., Graphical abstract PAINS result in nonspecific interactions or other undesirable effects. The use of “Fair Trial Strategy” to identify interesting molecules in PAINS to provide certain structure‒function insight in multitarget-directed ligand (MTDL) development.Image 1

The treatment of migraine is often complicated by insufficient headache relief, a miscellany of side effects and the risk of developing Medication Overuse Headache (MOH). Novel acute therapies have been recently developed and are now in the early post-marketing phase. Lasmiditan is a highly selective serotonin receptor agonist that binds to the 5-HT1F receptor, while ubrogepant and rimegepant antagonize the calcitonin gene-related peptide receptor. All three medications are now prescribed in a real-world setting, and an adequate level of knowledge is the starting point for rational use. In this rapid systematic review, we have established what is known about lasmiditan, ubrogepant and rimegepant, highlighting the most relevant safety aspects available from published studies and speculating about their risk of MOH.

This letter reports a sequential triple “click” chemistry method for the precise synthesis of functional polyhedral oligomeric silsesquioxane (POSS)-based multiheaded and multitailed giant surfactants. A vinyl POSS-based heterobifunctional building block possessing two alkyne groups of distinct reactivity was used as a robust and powerful “clickable” precursor for ready access to a variety of POSS-based shape amphiphiles with complex architectures. The synthetic approach involves sequentially performed strain-promoted azide–alkyne cycloaddition (SPAAC), copper-catalyzed azide–alkyne cycloaddition (CuAAC), and thiol–ene “click” coupling (TECC). Specifically, the first SPAAC reaction was found to be highly selective with no complications from the vinyl groups and terminal alkynes in the precursor. The method expands the toolbox of sequential “click” approaches and broadens the scope of synthetically available giant surfactants for further study on structure–property relationships.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity. This thesis describes the discovery of LEI-515 as peripherally restricted, reversible MAGL inhibitor. A library of 233.820 compounds was screened at the Pivot Park Screening Center and 7 hits were confirmed. Over 100 analogues of the most promising hit were designed, synthesized and evaluated in a natural substrate assay and activity-based protein profiling. This resulted in the identification of LEI-515, which has subnanomolar inhibitory potency, high selectivity and good metabolic stability. LEI-515 is a reversible inhibitor that forms a hemiketal with catalytic Ser122, stabilized by hydrogen bonds with Ala53 and Met123. LEI-515 is > 100-fold selective over a panel of 44 ion channels, receptors and enzymes, including the cannabinoid CB1 and CB2 receptor, hERG and cyclooxygenases. Targeted lipidomics revealed that LEI-515 increased cellular 2-AG levels in a concentration and time-dependent manner. Pharmacokinetic studies indicated that LEI-515 has excellent oral bioavailability, but does not penetrate the brain.

Production of functional molecules from renewable bio-feedstocks and bio-waste has the potential to significantly reduce the greenhouse gas emissions. However, the development of such processes commonly requires invention and scale-up of highly selective and robust chemistry for complex reaction networks in bio-waste mixtures. We demonstrate an approach to optimising a chemical route for multiple objectives starting from a mixture derived from bio-waste. We optimise the recently developed route from a mixture of waste terpenes to p-cymene. In the first reaction step it was not feasible to build a detailed kinetic model. A Bayesian multiple objectives optimisation algorithm TS-EMO was used to optimise the first two steps of reaction for maximum conversion and selectivity. The model suggests a set of very different conditions that result in simultaneous high values of the two outputs.

Spermine and spermidine serve as the key biomarkers for early-stage cancer diagnosis. This work reports a rapid, highly selective, and noninvasive sensing platform for spermine/spermidine. The hybrid material, developed in this work, has been characterized by UV-vis, IR, powder XRD, SEM, EDX, and rheological studies. Storage modulus (

Here, we designed a target-initiated, enzyme-free DNA cascade circuit for highly selective and sensitive detection of Hg2+ with dual amplification based on concatenated fuel stimulant powered (FSP)...

Monoclonal antibodies (mAbs) are key components of revolutionary disease immunotherapies and are also essential for medical diagnostics and imaging. The impact of cost is illustrated by a price$200,000 per year per patient for mAb-based cancer therapy. Purification represents a major issue in the final cost of these immunotherapy drugs. Protein A (PrA) resins are widely used to purify antibodies, but resin cost, separation efficiency, reuse, and stability are major issues. This paper explores a synthesis strategy for low-cost, reusable, stable PrA-like

Silicon-based hybrid nanoparticles have gained much attention because of their extensive biomedical applications. The superiority of the silicon-based hybrid nanoparticles over the other hybrid nanoparticles lies in their excellent barrier properties, light weight, and reinforcement of mechanical performance. The hybrid nanoparticles of silicon also have enhanced biological properties, and hence they can be used as biosensors. The biosensor is an integrated device that provides the specific quantitative analytical information with the help of a bioreceptor. Due to the highly selective nature of the recognition element toward the target analyte, the biosensor shows better results in comparison with the chemical sensors. The high specificity, reusability, sensitivity, and compact size of the biosensor are the enhanced properties of the sensing device, which makes the biosensor an attractive alternative to the conventionally used techniques. An optical sensor made through the utilization of hybrid nanoparticles of silicon has been already reported for the sensing of virus, antibody, DNA, and other small analytes.

The activity analysis of proteome-wide action of small reactive molecules infers their biological consequences and has a profound impact on human health. These analyses utilize and stimulate technological advances in chemical proteomics. This chapter primarily describes a new α-methylene-β-lactone (MeLac) alkyne probe (MeLacA) as a broadly reactive probe for chemical proteomics measurements. It discusses the reactivity of MeLacA in comparison with widely used iodoacetamide and fluorophosphonate probes. The use of probes of broad reactivity empowers adaptable competitive chemical proteomics platforms for subtractive analysis of proteome-wide reactions of small reactive molecules. The MeLac probe has multiple electrophilic sites. The probe MeLacA recruits glutathione in live cells to form a selective β-lactone probe, demonstrating a modular concept of rapidly developing highly selective chemical probes from an existing multi-electrophilic scaffold. This chapter concludes with some of our perspectives on chemical proteomics measurements and the promise of using scaffold probes to develop new covalent proteomics probes for precisely analyzing the proteome's activity domain within a zoomable scope.

Expansion Microscopy (ExM) significantly improves the resolution of conventional diffraction-limited optical microscopy by using physically expanding biological samples. Combining ExM with single molecule localization microscopy (SMLM) could further enhance the resolving power of SMLM, which is typically on the order of 20-30 nm. However, to make this combination successful, we need to solve three key issues related to sample preparation, including mainly hydrogel shrinking in ionic photoswitching buffer, fluorescence photobleaching due to free-radical reaction and reduced labelling efficiency from protease digestion. Using polyacrylamide gel re-embedding or improved photoswitching buffer with low ionic strength are able to minimize or even solve the hydrogel shrinking problem, while the development of post-expansion labelling approaches avoids fluorescence bleaching. However, the preservation of protein epitopes (which determines the labelling efficiency) remains to be challenging. In this paper, we propose to tackle this challenge by inserting the highly selective and stable biotin-streptavidin interaction into the post-expansion labelling strategy. After upgrading the popular immunolabelling linkage scheme from Epitope-Primary antibody-Secondary antibody-Fluorophores to Epitope-Primary antibody-Secondary antibody-Biotin-Streptavidin-Fluorophores, we are able to label protein epitopes with Biotin, which is stable during the expansion process, and thus avoid the troublesome problem in preserving protein epitopes or antibody. We demonstrate that combining Ex-SMLM with the new post-expansion linkage scheme enables new possibility in resolving the detailed arrangement of the Nup133 proteins in nuclear pore complex, which helps researchers observe a clearer structure. This study provides new chances for studying the ultrastructural details of subcellular organelles or even biomacromolecules, using conventional SMLM system.

In this paper, a fluorescent aptamer sensor was constructed based on the carbon dots and graphene oxide. This sensor combines the excellent fluorescence performance of carbon dots with the high specificity of aptamers to detect progesterone with high sensitivity and selectivity. In the absence of progesterone, the carbon dots-aptamer system and graphene oxide form a fluorescence resonance energy transfer process(FRET), which quenches the fluorescence of the carbon dots. When progesterone is added, the aptamer specifically binds to progesterone, resulting the fluorescence of the carbon dots is recovered. At optimal conditions, the fluorescence intensity recovered by the carbon dots has a linear relationship with the concentration of progesterone in the range of 0.1-120 nM, and the detection limit is 3.3×10 -11 M. Besides, the sensor has satisfactory detection results of progesterone in milk, indicating that this method has a enormous potential for application in food safety.

A non-enzymatic electrochemical sensor for glucose detection is executed by using a conductive metal–organic framework (MOF) Cu-MOF, which is built from the 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) ligand and copper acetate by hydrothermal reaction. The Cu-MOF demonstrates superior electrocatalytic activity for glucose oxidation under alkaline pH conditions. As an excellent non-enzymatic sensor, the Cu-MOF grown on Cu foam (Cu-MOF/CF) displays an ultra-low detection limit of 0.076 μM through a wide concentration range (0.001–0.95 mM) and a strong sensitivity of 30,030 mA μM−1 cm−2. Overall, the Cu-MOF/CF exhibits a low detection limit, high selectivity, excellent stability, fast response time, and good practical application feasibility for glucose detection and can promote the development of MOF materials in the field of electrochemical sensors.

OX1 receptor antagonists are of interest to treat, for example, substance abuse disorders, personality disorders, eating disorders, or anxiety-related disorders. However, known dual OX1/OX2 receptor antagonists are not suitable due to their sleep-inducing effects; therefore, we were interested in identifying a highly OX1 selective antagonist with a sufficient window to OX2-mediated effects. Herein, we describe the design of highly selective OX1 receptor antagonists driven by the X-ray structure of OX1 with suvorexant, a dual OX1/OX2 receptor antagonist. Moderately selective OX1 antagonists comprising a [2.2.1]-bicyclic scaffold served as our starting point. Based on our binding mode hypothesis, we postulated which part of the scaffold points toward one of the regions where the two binding pockets differ. Structural changes in this part resulted in a modified core with higher inherent selectivity compared to the [2.2.1]-bicyclic template. The structure-based design, synthesis, and hit-to-lead evaluation of this novel OX1 receptor-selective scaffold are discussed herein.