High Selectivity Research Articles

Combinatorial Pattern Response of Bioelectronic Nose for the Detection of Real Nerve Agents.

Nerve agents are toxic organophosphorus chemicals and acetylcholinesterase inhibitors that have been used in terrorist acts. Because they exhibit fatal toxic effects in small amounts, technology is required to detect and identify them early. Research for nerve agent detection using structural simulants of real agents may not function properly for real agents depending on the selectivity of the sensor. For practical sensor applications, experiments were conducted using two toxic nerve agents, sarin and VX, which are used in terrorism and attacks. Herein, human olfactory receptors (ORs) were used as sensing materials with high selectivity and sensitivity to target substances. Through molecular dynamic simulations, the interaction results between ORs and target materials were compared, and an OR combination that could distinguish structurally similar target materials was selected. Four types of OR were combined with a graphene/MoS2-based n-type field-effect transistor platform to create a bioelectronic nose that showed remarkable sensitivity and a stable basal current to convert the biological signals of the OR with target substances into electrical signals. This study developed a nerve agent detection technology using multiple OR sensing signals, advocating combinatorial pattern recognition, which is the core of the human olfactory mechanism. The bioelectronic nose effectively distinguishes structurally similar nerve agents using pattern signals.

Inhibition of Kornblum Reaction with Lithium Salts in SN2 Reactions of Sulfonates and a Nucleophile Containing a Pyridine N-Oxide Moiety: Convergent and Selective Synthesis of an MRGPRX2 Antagonist.

A critical step in the development of a convergent synthesis of an MRGPRX2 antagonist (1) was the SN2 reaction with a highly functionalized lactamide electrophile and a unique difluoropiperidine nucleophile containing a pyridine N-oxide moiety. Initial reactions with sulfonate leaving groups exhibited superb stereoselectivity, but yields were very low due to side reactions originated from competitive Kornblum reactions of the pyridine N-oxide and the sulfonates. Markedly improved reaction profiles were achieved by including stoichiometric lithium triflate. NMR data provided insights into how the lithium cation impacted the pyridine N-oxide through coordination and attenuating its nucleophilicity, leading to the inhibition of the undesired Kornblum reactions. Our approach is highly relevant to preservation of the N-oxide, a structural motif known to several marketed products and emerging as an important class in drug discovery in nucleophilic substitutions. Application of this method enabled the production of the target (1 and its HCl salt 1a) up to multikilogram scale with high selectivity and in much improved yield.

Eco-friendly four spectrophotometric approaches for the simultaneous determination of the recently FDA-approved combination, bupivacaine and meloxicam in pharmaceutical dosage forms

In this study, bupivacaine (BUP) and meloxicam (MLX) were simultaneously assayed in their co-formulated ampoules without interference using four affordable, sensitive, and eco-friendly spectrophotometric methods. The assay of MLX at 359.3 nm over the concentration range of 1.0–15.0 µg/mL was accomplished using a direct UV-spectrophotometric method (Method I) without interference from BUP. However, there was a significant overlap between the spectra of BUP and MLX, making it difficult to determine BUP directly from the UV spectrum. Therefore, various UV-based techniques, including second derivative spectrophotometry (Method II), ratio subtraction method (Method III), and absorption factor method (Method IV), were used to determine BUP over the concentration range of 5.0–80.0 µg/mL. The proposed methods could simultaneously determine the studied drugs with a challenging ratio of 33.3:1.0 (BUP: MLX), which increases the importance of the current study. The proposed methods were applied to estimate the studied drugs in commercial ampoules with high % recoveries and low %RSD values. The excellent eco-friendliness of the developed methods was demonstrated using GAPI and AGREE metrics. The developed methods were validated according to ICHQ2(R2) guidelines. The proposed methods can be better suited for the routine analysis of BUP and MLX in their fixed-dose combination with high selectivity.

Nanomaterial-Based Electrochemical Sensors for the Detection of Pharmaceutical Drugs

The rapidly increasing human population has led to new biological and environmental challenges. These challenges, in turn, have contributed to the rapid growth of the pharmaceutical sector. Quality control in pharmaceutical manufacturing and drug delivery necessitates portable, sensitive, precise, and cost-effective devices to monitor patient dosing and assess pharmaceutical hazards. This study highlights the attributes and applications of the current nanomaterial-based sensors for drug detection, emphasizing the potential of these devices to advance the detection of bioactive molecules, thereby promoting human health and environmental protection on a large scale. Electrochemical sensors, in particular, have become invaluable in bioimaging, electrochemical analysis, and drug delivery due to their high specificity, selectivity, and stability across cycles. This review focuses on recent advancements in electrochemical devices for healthcare applications, detailing their production, analytical performance, and clinical uses.

A General Hydrotrifluoromethylation of Unactivated Olefins Enabled by Voltage‐Gated Electrosynthesis

AbstractHere we present the first successful hydrotrifluoromethylation of unactivated olefins under electrochemical conditions. Commercially available trifluoromethyl thianthrenium salt (TT+−CF3BF4−, Ep/2=−0.85 V vs Fc/Fc+) undergoes electrochemical reduction to generate CF3 radicals which add to olefins with exclusive chemoselectivity. The resulting carbon centered radical undergoes a second cathodic reduction, instead of a classical HAT process, to generate a carbanion that can be terminated by protonation from solvent. The use of MgBr2 (+0.20 V onset oxidation potential) plays a key role as an enabling sacrificial reductant for the reaction to operate in an undivided cell. Guided by cyclic voltammetry (CV) studies, fine‐tuning the solvent system, trifluoromethylating reagent's counteranion and careful selection of redox processes, this work led to the development of a voltage‐gated electrosynthesis by pairing two redox processes with a narrow potential difference (ΔE≈1.00 V) allowing the reaction to proceed with two important advances: (a) high reactivity and selectivity towards hydrotrifluoromethylation over undesired dibromination, and (b) an unprecedented functional group tolerance, including aniline, phenols, unprotected alcohol, epoxide, trialkyl amine, and several redox sensitive heterocycles.

Unveiling the Structural Effects in Hybrid Copper Phosphonate Frameworks for Selective Electrocatalytic CO2 Reduction Reaction.

Electrochemical CO2 reduction holds tremendous promise for transforming carbon dioxide into several value-added energy feedstocks and utilizing renewable energy sources. Herein, we have developed two novel copper-based organophosphonates for selective electrocatalytic conversion of CO2 to CH3OH conversion. The two-dimensional layer structure of Cu3[(Hhedp)2(C4H4N2)].2H2O (I) and the three-dimensional Cu3[(H3hedp)2(C4H4N2)4(SO4)].2H2O (II) have been isolated as single crystals via a hydrothermal strategy. Compound I consists of Cu2+ oxidation states exclusively, while compound II has Cu1+ oxidation states in a network wherein a Cu2+-phosphonate template is embedded inside the framework. Depending on mixed valent oxidation states, compound II exhibits high selectivity compared to compound I for the electrocatalytic reduction of CO2 to CH3OH (C1) as the primary product and CH3COOH (C2) as the secondary product. Notably, product selectivity is enhanced as the Faradaic efficiency (FE) of the competing hydrogen evolution reaction (HER) is significantly reduced in compound II relative to that of I, particularly at higher applied reduction potentials. The optimal ratio of Cu1+ active sites in compound II plays a pivotal role in enhancing methanol selectivity, stabilizing critical intermediates, and maintaining ideal reduction potentials as a noble-metal free electrocatalyst. Moreover, the optical band gap and the Mott-Schottky measurements further suggest the title Cu-phosphonate materials could be promising and effective photocatalysts.

DDEL-02. PRECLINICAL EFFICACY OF IL13RΑ2-TARGETING POLYPEPTIDE-DRUG CONJUGATE (SELF-DEPOTTM ONCOPDC) IN GLIOBLASTOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA

Abstract Glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) are currently incurable cancers. Systemic chemotherapy shows limited efficacy because of the intact blood-brain barrier. Convection-enhanced delivery (CED) offers promise by concentrating high doses of chemotherapeutics directly within these tumors. However, drugs administered via CED often face challenges in confirming precise target delivery and are quickly cleared by increased interstitial fluid flow and drug efflux transporters. This highlights the urgent need for innovative drugs that demonstrate target specificity and prolonged retention capabilities. Intrinsically disordered polypeptides (IDPs), derived from tropoelastin, self-assemble into water-insoluble structures with extended retention properties triggered by body temperature. IL13Rα2, differentially amplified in U87MG GBM and SF8628 DIPG cells, serves as a target for therapeutic intervention. An IL13Rα2-targeting IDP (XM161) was developed by incorporating IL13Rα2 binding sequences into the IDP domains. XM161 demonstrated high selectivity in binding to IL13Rα2, with Kd values of 1,786 nM for IL13Rα1 and 12.8 nM for IL13Rα2. Conjugation of XM161 with SN38, a potent topoisomerase I inhibitor, resulted in XM161-SN38, which remained in a dissolved state up to 50°C but formed insoluble aggregates above 27°C in the presence of cerebrospinal fluid. XM161-SN38 exhibited strong cytotoxicity against U87MG and SF8628 cells, with IC50 values of 14.2 nM and 0.48 nM, respectively. Importantly, XM161-SN38 demonstrated efficacy in overcoming Temozolomide resistance in T98G GBM cells, with IC50 values of 3.35 nM compared to 10.87 nM for unconjugated SN38. In orthotopic xenograft models established in BALB/cSlc-nu/nu male mice using U87MG-Luc2 cells, three doses (3 x 0.95 μg SN38 equivalents) of XM161-SN38 delivered via CED were well tolerated and significantly extended median survival to over 65 days, providing a notable survival benefit compared to untreated controls (42 days) and Topotecan-treated group (42.5 days). These findings validate the feasibility and therapeutic potential of XM161-SN38 for GBM treatment. Ongoing studies are underway to investigate the safety and pharmacokinetics of XM161-SN38 in tumor-naive mouse brains.

Advances in Carbon Dot Based Enhancement of Photodynamic Therapy of Tumors.

Photodynamic therapy has advantages of high selectivity, less invasiveness, and high lethality for cancer cells compared with traditional treatment methods. However, some problems have hindered the development of photodynamic therapy, such as limited penetration depth, lack of oxygen, and toxicity. Carbon dots are widely used in the imaging and treatment of tumors due to their excellent optical and physicochemical properties, so effective methods have been explored to address the issues in photodynamic therapy via carbon dots. This review aims to elucidate the role of carbon dots in photodynamic therapy of cancer. Moreover, we summarize and discuss some strategies to harness carbon dots to enhance photodynamic therapy. Finally, we summarize many cancer synergistic therapeutic modalities involving carbon dots such as chemodynamic therapy, photothermal therapy, and immunotherapy in combination with photodynamic therapy to achieve more effective and safer treatments.

Terahertz time-domain investigation of atacamite: Spectral analysis and theoretical insights for cultural heritage applications

Spectroscopic methods based on terahertz (THz) radiation can represent an innovative approach in the Cultural Heritage field. Specifically, contemporary and historical pigments can exhibit unique fingerprints. However, despite the high selectiveness of terahertz technique, the origin of spectral characteristics is not often known. In this work, the characteristic terahertz-time-domain spectroscopy spectrum of atacamite is reported in the spectral range 0.1–3.7 THz along with ab initio calculation of lattice dynamics to assess the nature of experimental features. The obtained results enable the acquisition of reliable new data in Heritage sciences, which is essential for developing accurate reference pigment databases.

Aromatic Amino Acid Hydroxylases as Off-Targets of Histone Deacetylase Inhibitors.

The aromatic amino acid hydroxylases (AAAHs) phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylases 1 and 2 are structurally related enzymes that contain an active site iron atom and depend on tetrahydrobiopterin (BH4) as cosubstrate. Due to their important roles in synthesis of serotonin, dopamine, noradrenaline, and adrenaline and their involvement in cardiovascular, neurological, and endocrine disorders, AAAHs have been targeted by substrate analogs, iron chelators, and allosteric ligands. Phenylalanine hydroxylase is also off-target of the histone deacetylase (HDAC) inhibitor panobinostat. To systematically explore the binding of HDAC inhibitors to AAAHs, we screened a library of 307 HDAC inhibitors and structural analogs against tryptophan hydroxylase 1 using a fluorescence-based thermal stability assay, followed by activity assays. Selected hits were enzymatically tested against all four purified human AAAHs. Cellular thermal shift assay was performed for phenylalanine hydroxylase. We show that panobinostat and structurally related compounds such as TB57, which similarly to panobinostat also contains a cinnamoyl hydroxamate, bind to human AAAHs and inhibit these enzymes with high selectivity within the class (panobinostat inhibition (IC50): phenylalanine hydroxylase (18 nM) > tyrosine hydroxylase (450 nM) > tryptophan hydroxylase 1 (1960 nM). This study shows that panobinostat and related hydroxamic acid type HDAC inhibitors inhibit all AAAHs at therapeutically relevant concentrations. Our results warrant further investigations of the off-target relevance of HDAC inhibitors intended for clinical use and provide directions for new dual HDAC/AAAH and selective AAAH inhibitors. These findings may also provide a new mechanistic link between regulation of histone modification, AAAH function, and monoaminergic neurotransmission.

High-Extinction Photonic Filters by Cascaded Mach–Zehnder Interferometer-Coupled Resonators

In this study, we demonstrate high-extinction stop-band photonic filters based on Mach–Zehnder interferometer (MZI)-coupled silicon nitride (Si3N4) resonators fabricated using I-line lithography technology. Leveraging the low-loss silicon nitride waveguide, our approach enables the creation of stable, high-performance filters suitable for applications in quantum and nonlinear photonics. With destructive interference at the feedback loop, photonic filters with an extinction ratio of 35 dB are demonstrated with four cascaded MZI-coupled resonators. This cascading design not only enhances the filter’s extinction but also improves its spectral sharpness, providing a more selective stop-band profile. Experimental results agree well with the theoretical results, showing linear scaling of extinction ratios with the number of cascaded MZI-coupled resonators. The scalability of this architecture opens the possibility for further integration and optimization in complex photonic circuits, where high extinction ratios and precise wavelength selectivity are critical for advanced signal processing and quantum information applications.

Design of a quad-band bandpass filter based on 13-mode resonator

ABSTRACT A quad-band microstrip bandpass filter (BPF) based on a 13-mode resonator is proposed in this article with compact size, high band‐to‐band isolation, and multiple transmission zeros (TZs). The proposed filter is constructed by two transmission paths from the input to the output port, which employs the transversal cancellation mechanism of two transition paths to introduce extra nine TZs. Therefore, a total of 12 TZs are located at 0.2, 1.8, 2, 3.88, 4.61, 5.24, 5.9, 9.26, 9.51, 12.32, 12.75, and 13.27 GHz, respectively, realizing high selectivity. Moreover, the designed filter can achieve quad passbands with centered frequency at 0.95, 2.78, 7.32, and 10.63 GHz for the requirement of multi-service in modern communication systems, with wide bandwidth of 235, 790, 2200, and 1540 MHz, respectively. The measured results agree well with the simulation results, which proves the feasibility of the design method.

Polysaccharide Functionality in Wine-like Model Systems with Oat and Egg White Model Proteins

Interactions between wine proteins and polysaccharides have the capacity to regulate the stability, shelf-life, and turbidity of red wines. Understanding these macromolecular interactions helps with maintaining stability and reproducing high quality wines. Model polysaccharides (carboxymethyl cellulose, mannoproteins, and fruit pectin) and model proteins (egg white and oat protein) were selected to assess protein–polysaccharide interactions within a model wine solution. The wine-like solution was created to simulate the correct pH, ethanol strength, and pigment content. Any interactions with polymeric pigments—anthocyanins and tannins—can also be investigated in this matrix. To analyze the aggregative potential of the macromolecules, particle size and Zeta-potential (ζ-potential) measurements were recorded for the samples with increasingly complex compositions. Carboxymethyl cellulose was found to increase particle sizes, likely binding more than proteins, but also improved the overall stability of the solution. Fruit pectin and mannoprotein were effective at causing precipitation while not removing the color of the model wine. The use of mannoprotein ensued in overall smaller particles for both suspended aggregate and precipitate sizes, indicating higher selectivity. Fruit pectin increased precipitate sizes and decreased suspended aggregate sizes. This study implements model proteins to evaluate complex macromolecular interactions using measurements of ζ-potential and particle size.

Cu−Bi Bimetallic Catalysts Derived from Metal–Organic Framework Arrays on Copper Foam for Efficient Glycine Electrosynthesis

AbstractGlycine as one of the most abundant amino acids in human proteins, with extensive applications in both life and industry, is conventionally synthesized through complex procedures or toxic feedstocks. In this study, we present a facile and benign electrochemical pathway for synthesis of glycine through reductive coupling of glyoxylic acid and nitrate over a copper‐bismuth bimetal catalyst derived from a metal–organic framework (MOF) array on copper foam (Cu/Bi−C@CF). Remarkably, Cu/Bi−C@CF achieves a fantastic selectivity of 89 %, corresponding a high Faraday efficiency of 65.9 %. From control experiments, the introduction of Bi caused the binding energy of Cu shift to a lower state, which leads to a high selectivity towards the formation of key intermediate hydroxylamine rather than ammonia product, facilitating the formation of oxime and providing additional sites for subsequent hydrogenation reaction on the way to glycine. Moreover, the derivation of MOF arrays ensures the effective dispersion of Bi and enhances the stability of Cu/Bi−C@CF. This innovative approach not only presents sustainable pathways for the production of value‐added organonitrogen compounds utilizing readily available carbon and nitrogen sources, but also provides novel insights into the design of multistage structural catalysts for sequential reactions.

Fenton-Inactive Cd Enables Highly Selective O2-Derived Domino Reaction.

Advancing and deploying Fenton-inactive Cd that combines excellent catalytic activity, selectivity, and stability remains a serious challenge, predominantly owing to the difficulty in regulating the intrinsic electronic states and local geometric structures of such fully occupied d10s2 configuration. In this work, a combination of experiments and theoretical calculations reveals that the incorporation of boron (B) enables the tuning of the average oxidation state of Cd0 to Cdδ+, facilitating electron localization and implementing a different electrocatalytic preference compared to conventional d10-electron configurations. The resulting Cd(B) catalyst demonstrates high selectivity (>90% on average) in the O2-to-H2O2 conversion, negligible activity loss over 100h, and a superior H2O2 production rate (15.5mol∙gcat -1h-1 at -100mA). More unexpectedly, the in situ generated H2O2 exhibits a unique advantage over commercial products, selectively oxidizing cinnamaldehyde to benzaldehyde by modulating the practical current.

Ortho Arylation of N-Aryl Amides and the Construction of Diagonal Tetraarylbenzenediamines and N-Doped Fulminenes via BBr3-Derived Dibromoboracycles.

The synthesis of biaryl amides, which are prevalent motifs in bioactive molecules, often necessitates lengthy and inefficient procedures. To address these limitations, catalytic C-H activation protocols have emerged, enabling the direct ortho-arylation of aryl amides. However, these protocols often suffer from issues such as lack of selectivity, reliance on stoichiometric oxidants, and the requirement for excess reagents and harsh reaction conditions. To overcome these challenges, we present a novel and highly selective protocol for the ortho-arylation of N-aryl amides and ureas. The high selectivity originates from the directed installation of BBr3 to form a boracycle, which then undergoes cross-coupling with an aryl halide. Our method offers significant advantages, including mild reaction conditions, excellent site-specificity, and scalability. The protocol demonstrates broad compatibility with a diverse range of readily accessible functionalized anilides and aryl iodides, as evidenced by 55 successful examples yielding products in the 30-95% range. Furthermore, our methodology surpasses conventional approaches by facilitating the one-pot selective diagonal diarylation of dianilides. This capability unlocks the construction of previously unattainable diagonal aryl systems, which serve as valuable precursors for the synthesis of diagonal tetraarylbenzenediamines and N-doped fulminene, two crucial compound classes in materials science.

Enhancing Gene Delivery in NB-4 Cells: Overcoming Transduction and Selection Challenges

Efficient gene transduction and cell viability are critical factors in genetic manipulation for research and therapeutic purposes. In this study, we explored the challenges associated with transducing the NB-4 cell line, a well-established model for acute promyelocytic leukemia (APL), using lentiviral vectors. While the initial transduction efficiency in NB-4 cells reached approximately 30%, we observed a significant decrease in cell viability, a phenomenon not observed in other acute leukemia cell lines such as THP-1 cells. We identified that this toxicity could be mitigated by purifying viral particles through ultracentrifugation or polyethylene glycol (PEG) precipitation, indicating that toxic substances, potentially secondary metabolites released by HEK293, could be responsible for the cell death. Nevertheless, cell selection by puromycin was still ineffective; crucially, we discovered that the human phosphoglycerate kinase (hPGK) promoter, commonly used in the PLKO1 vector, may become silenced in NB-4 cells, preventing effective selection with puromycin. By replacing the hPGK promoter with the elongation factor-1 alpha (EF1α) promoter, we successfully achieved high transduction efficiency and robust selection, demonstrating the potential for this modified vector system to facilitate genetic studies in APL models. These findings provide important insights into optimizing gene transduction protocols not only for NB-4 cells but also for other challenging cell lines, offering a refined approach for gene delivery and selection in cell models.

Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP.

The E3 ligase HOIP is vital for the NF-κB pathway and is implicated in cancer and immunity. However, it remains challenging to achieve high selectivity by directly targeting the conserved catalytic RBR domain of HOIP. Herein, we identified four low-molecular-weight compounds that bind to an uncharacterized pocket of the HOIP PUB domain (HOIPPUB). The complex structure facilitated the discovery of the first single-digit micromolar ligand of HOIPPUB, tolfenamic acid, which exhibited over 30-fold selectivity due to the low sequence identity of the uncharacterized pocket of HOIPPUB. Although tolfenamic acid did not block the substrate recognition and linear ubiquitination activity of HOIP, a ligand of the uncharacterized PUB pocket of HOIP (LUPH), by chemical linking pomalidomide with tolfenamic acid, degraded HOIP, reduced NEMO ubiquitination and p65 phosphorylation, and eventually inhibited NF-κB activation and breast cancer cell proliferation. Our work proposes an alternative strategy to target the nonfunctional pocket of the PUB domain with high sequence diversity to promote HOIP degradation, rather than targeting the conserved RBR domain to block the catalytic function of HOIP.

“Social Elevator”: Research of Affirmative Action Program

This work investigates the academic performance of students enrolled in the “Social Elevator” program at Higher School of Economics (HSE University), which operates under the principle of affirmative action and aims to assist those students who have lower chances of admission due to various social reasons in a highly competitive environment. Objective admissions in Russian universities and the high selectivity of the HSE University, discussed in this paper, do not confidently allow the application of conclusions from foreign studies to the Russian experience. The program had not been previously researched. It was assumed that students of the program would show higher performance than their peers admitted on a general basis – this assumption follows from qualitative research that found that students of this program possess a progressive narrative of overcoming inequality. Regression with dummy variables based on administrative data on student performance and survey data on the socio-economic status of students are used for the analysis. According to the regression analysis results, all else being equal, students of the “Social Elevator” program demonstrate lower performance than students admitted on budgetary places on general grounds, although they average grades at the “good” level and therefore have a chance to get a return to education and overcome inequality. Further research on the topic is required to separate the secondary effects of inequality, as well as to assess the actual social mobility of students participating in the program. The results can be useful in designing educational policy in the field of expanding access to higher education.

High Selectivity CO2 Hydrogenation to Liquid Fuel Over NaFeZnMn Catalyst

High Selectivity CO2 Hydrogenation to Liquid Fuel Over NaFeZnMn Catalyst