Search

Rationale: The study of inherent stability characteristics of drugs has been advocated to be important by various regulatory agencies like the ICH, USFDA, and others. The current work was envisaged to investigate the forced degradation profile of the drug ivacaftor under ICH-prescribed stress conditions, identification of its potential degradants, and postulation of the degradation routes for their generation., Methods: The stress degradation studies were performed on the drug as per the ICH guideline Q1A(R2). A UPLC-photodiode array-based chromatographic method was developed to satisfactorily resolve the drug from its degradation products, validated in accordance with various ICH prescribed parameters, and assessed for its BAGI practicality index. The degradation products were identified and characterized by UPLC-ESI-QTOF-MS studies., Results: The drug was found to significantly degrade under conditions of alkaline hydrolytic stress and it was found to be stable under all other stressor environments including acid/neutral hydrolytic, photolytic, thermal, and oxidative stress. Four alkaline hydrolytic degradation products (I-IV) were revealed by UPLC-QTOF-MS studies which were well-resolved from the drug over a C18 UPLC column by the developed UPLC-PDA method. The detection wavelength was selected as 310 nm. Characterization of the four degradation products (I-IV) was carried out by their mass spectral data and their respective degradation routes were elucidated., Conclusions: A UPLC-PDA method was developed and validated for ivacaftor and its practicality BAGI index was computed. Four alkaline hydrolytic degradation products of ivacaftor were revealed through UPLC-ESI-QTOF-MS studies and corresponding degradation routes were elucidated., (© 2024 John Wiley & Sons Ltd.)

A transmission detection mode was investigated with SERS analyses (SETRS). A comparison between backscattering and transmission detection modes was conducted to demonstrate the feasibility of performing SETRS analyses. The impact of various parameters on the SERS signal intensity such as sample volume, lens collection optic, laser beam size and laser power were then examined. The analytical performances of SETRS were further evaluated through the quantification of an impurity (4-aminophenol) ranging from 3 to 20 µg/mL in a commercial pharmaceutical product using a total error risk-based approach. To account for expected variability of routine analysis, 9 batches of silver nanoparticles suspensions were used and experiments were performed over 5 different days and by 2 operators. Univariate spectral analysis based on a quadratic regression was compared to a multivariate approach using a partial least square regression. The presented results demonstrated that SETRS can be used to determine an impurity in a complex matrix opening new perspectives for quantitative applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One of the most essential chemical processes that is utilized in the manufacturing of a great deal of contemporary goods is called heterogeneously catalyzed reactions, and it is also one of the most fascinating. Metallic nanostructures are heterogeneous catalysts for range reactions due to their huge surface area, large assembly of active surface sites, and quantum confinement effects. Unprotected metal nanoparticles suffer from irreversible agglomeration, catalyst poisoning, and limited life cycle. To circumvent these technical disadvantages, catalysts are frequently spread on chemically inert materials like as mesoporous Al2O3, ZrO2, and different types of ceramic material. In this research, plentiful bauxite residue is used to create a low-cost alternative catalytic material. We have hydrogenated p-Nitrophenol to p-Aminophenol on bauxite residue (BR) supported silver nanocomposites (Ag NCs). The phase and crystal structure, bond structure and morphological analysis of the developed material will be done XRD, FTIR, and SEM-EDX respectively. The ideal conditions were 150 ppm of catalyst, 0.1 mM of p-NP, and 10 minutes overall up-to 99% conversion of p-NP to p-AP. A multi-variable predictive model created using Response Surface Methodology (RSM) and a data-based Artificial Neural Network (ANN) model were found to be the best ways to predict the maximum conversion efficiency. ANN models predicted efficiency more accurately than RSM models, and the strong agreement between model predictions and experimental data was indicated by their low relative error (RE0.10), high regression coefficient (R2>0.97), and Willmott-d index (dwill-index > 0.95) values.

Enzymatic cascade reactions with high activity and specificity in living cells always benefit from multicompartmentalized organelles that provide separately confined spaces for enzymes, avoiding their mutual interference to ensure the high-efficiency operation of necessary vital movements. Inspired by this, we designed a 3D spherical microreactor (Au@H-APF@Pt) with biomimetic cascade catalysis for glucose detection. First, ultrasmall gold nanoparticles were immobilized in situ on the internal cavities of hollow 3-aminophenol formaldehyde resin (H-APF) nanospheres, along with glucose oxidase activity. Then, platinum nanoparticles (PtNPs) with peroxide-like activity were reduced surrounding the outer layer of the H-APF nanospheres. Similar to the cell structure, different metal sites in this bifunctional microreactor operated independently, bringing higher catalytic activity and selectivity and thus being synergistically capable of a cascade reaction to catalyze the substrate for glucose detection. This cell-mimicking microreactor (Au@H-APF@Pt) was successfully applied in glucose colorimetric detection, showing a 1.9-fold activity enhancement compared to direct mixing (Au/Pt). The observed low catalytic activity was attributed to the extended time for transferring hydrogen peroxide (H 2 O 2 ) from Au NPs to the solution and then to PtNPs. Integrating a smartphone APP, a real-time, visual, and Au@H-APF@Pt-based hydrogel sensor for glucose detection was also proposed. Satisfactory results highlight that this cell-mimicking microreactor offers a very successful strategy to improve the efficiency of cascade catalysis systems in biosensing.

Laccase is well-known for its eco-friendly applications in environmental remediation and biotechnology, but its high cost and low stability have limited its practical use. Therefore, there is an urgent need to develop efficient laccase mimetics. In this study, a novel laccase-mimicking nanozyme (MBI-Cu) was successfully synthesized using 2-methylbenzimidazole (MBI) coordinated with Cu 2+ by mimicking the copper active site and electron transfer pathway of natural laccase. MBI-Cu nanozyme exhibited excellent catalytic activity and higher stability than laccase, and was utilized to oxidize a series of phenolic compounds. Environmental pollutant aminophenol isomers were found to display different color in solution when catalytically oxidized by MBI-Cu, which provided a simple and feasible method to identify them by the naked eye. Based on the distinct absorption spectra of the oxidized aminophenol isomers, a colorimetric method for quantitatively detecting o-AP, m-AP, and p-AP was established, with detection limits of 0.06 μM, 0.27 μM, and 0.18 μM, respectively. Furthermore, by integrating MBI-Cu-based cotton pad colorimetric strips with smartphone and utilizing color recognition software to identify and analyze the RGB values of the images, a portable colorimetric sensing platform was designed for rapid detection of aminophenol isomers without the need for any analytical instrument. This work provides an effective reference for the design of laccase nanozymes and holds significant potential for applications in the field of environmental pollutant monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The blood-based detection of Alzheimer's disease (AD) is becoming challenging since the blood-brain barrier (BBB) restricts the direct circulation of AD molecules in the blood, thereby precluding the detection of AD at an early-stage. Herein, we report the development of a novel CNT-metal-porous graphene hybrid (CNT-MGH) nano-interdigitated array (n-IDA) electrochemical 8-well biosensor for the successful early-stage diagnosis of AD from blood. Laser-induced graphene (LIG) technology has been used to fabricate the proposed CNT-MGH n-IDA 8-well sensor. Firstly, the electrochemical characterization ( i.e. , electrode gap, material composition, etc. ) of the proposed sensor was demonstrated by measuring p -aminophenol (PAP) with a limit of detection (LOD) of 0.1 picomole. Subsequently, the CNT-MGH n-IDA 8-well sensor was then used to diagnose AD via novel blood biomarkers p-Tau 217 and p-Tau 181 using an electrochemical enzyme-linked immunosorbent assay (e-ELISA) enzyme by-product PAP. During e-ELISA, the alkaline phosphatase enzyme (IgG-AP) tagged to the detection antibody produced an electroactive ELISA by-product PAP by reacting with the enzyme-substrate 4-aminophenyl phosphate (PAPP). Finally, the CNT-MGH n-IDA 8-well sensor was then used to measure the current generated by the redox reaction via the e-ELISA by-product PAP. While quantified, the proposed CNT-MGH n-IDA 8-well sensor successfully detected p-Tau 217 and p-Tau 181 proteins in blood with LODs of 0.16 pg ml -1 and 0.08 pg ml -1 , respectively.

A new method has been developed to improve the detection of norovirus (NoV) in complex fecal samples using nanocatalyst-based immunoassays. The method involves using multifunctional trimetallic nanoparticles, known as Ag@Fe 3 O 4 @Au NPs. These nanoparticles consist of a core of silver (Ag) and a shell of iron oxide (Fe 3 O 4 ) decorated with isolated gold nanoparticles (Au NPs). The nanoparticles have enhanced catalytic activity, making them an ideal nanocatalyst for reducing 4-nitrophenol (4-NP, yellow) to 4-aminophenol (4-AP, colorless). The developed Ag@Fe 3 O 4 @Au NPs-based immunoassay achieved a limit of detection (LOD) of 1.9 pg/mL for norovirus-like particles (NoV-LP) and 6.97 RNA copy number/mL for fecal NoV. In fecal sample analysis for NoV, a heat treatment at 65°C was necessary to prevent degradation of the target protein, ensuring sensitive detection. This work successfully combined multifunctional nanocatalysts for advanced immunoassays, which could contribute to developing nano-biosensing platforms., (© 2024 Wiley‐VCH GmbH.)

Aminophenol dioxygenases (APDO) are mononuclear nonheme iron enzymes that utilize dioxygen (O 2 ) to catalyze the conversion of o-aminophenols to 2-picolinic acid derivatives in metabolic pathways. This study describes the synthesis and O 2 reactivity of two synthetic models of substrate-bound APDO: [Fe II (Tp Me2 )( tBu2 APH)] (1) and [Fe II (Tp Me2 )( tBu APH)] (2), where Tp Me2  = hydrotris(3,5-dimethylpyrazole-1-yl)borate, tBu2 APH = 4,6-di-tert-butyl-2-aminophenolate, and tBu APH 2  = 4-tert-butyl-2-aminophenolate. Both Fe(II) complexes behave as functional APDO mimics, as exposure to O 2 results in oxidative CC bond cleavage of the o-aminophenolate ligand. The ring-cleaved products undergo spontaneous cyclization to give substituted 2-picolinic acids, as verified by 1 H NMR spectroscopy, mass spectrometry, and X-ray crystallography. Reaction of the APDO models with O 2 at low temperature reveals multiple intermediates, which were probed with UV-vis absorption, electron paramagnetic resonance (EPR), Mössbauer (MB), and resonance Raman (rRaman) spectroscopies. The most stable intermediate at -70 °C in THF exhibits multiple isotopically-sensitive features in rRaman samples prepared with 16 O 2 and 18 O 2 , confirming incorporation of O 2 -derived atom(s) into its molecular structure. Insights into the geometric structures, electronic properties, and spectroscopic features of the observed intermediates were obtained from density functional theory (DFT) calculations. Although functional APDO models have been previously reported, this is the first time that an oxygenated ligand-based radical has been detected and spectroscopically characterized in the ring-cleaving mechanism of a relevant synthetic system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nitrophenol is a hazardous substance that poses a threat to the environment and human health, and its treatment has attracted widespread attention. The purpose of this study is to establish an environmentally friendly α-amylase system for the hydrolysis of starch to reduce nitrophenol to aminophenol through cascade reactions. The α-amylase system was obtained through artificial antibody-antigen-directed immobilization, including the synthesis of artificial antibodies, synthesis of artificial antigens, and affinity assembly. In this process, catechol and protocatechuic aldehyde were used to prepare artificial antibodies and artificial antigens respectively through polymerization and Schiff base reactions. Then, artificial antibodies captured the catechol in the artificial antigen structure to form immobilized α-amylases. Compared with free α-amylase, the immobilized α-amylase showed a good reusability and excellent regenerative ability. Subsequently, the immobilized α-amylase were used in the reaction of catalyzing starch hydrolysis to synthesize 2-amino-4-methylphenol, and the yield of 2-amino-4-methylphenol was 58.88 ± 0.19 %. After 5 consecutive catalytic reactions, a yield of 47.61 ± 1.27 % can still be achieved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The paper reports on the preparation of cellulose nanocrystals/reduced graphene oxide matrix loaded with cuprous oxide nanoparticles (CNC/rGO-Cu 2 O) through a simple solvothermal method and its application for 4-nitrophenol reduction to 4-aminophenol using sodium borohydride. The CNC/rGO-Cu 2 O nanocomposite was formed chemically by first mixing CNC and graphene oxide (GO) followed by complexation of the negatively charged functional groups of CNC/GO with Cu 2+ ions and subsequent heating at 100°C. This resulted in the simultaneous reduction of GO to rGO and the formation of Cu 2 O nanoparticles. The as-elaborated nanocomposite was firstly characterized using different techniques such as atomic force microscopy, scanning electron microscopy, transmission electron microscopy, UV-Vis spectrophotometry, Raman spectroscopy and x-ray photoelectron spectroscopy. Then, it was successfully applied for efficient catalytic reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride: the reduction was completed in about 6 min. After eight times use, the catalyst still maintained good catalytic performance. Compared to CNC/rGO, rGO/Cu 2 O and free Cu 2 O nanoparticles, the CNC/rGO-Cu 2 O nanocomposite exhibits higher catalytic activity even at lower copper loading., (© 2024 Wiley Periodicals LLC.)

Mesenchymal stem cells (MSCs) have emerged as an indispensable source for stem cell research and preclinical studies due to their capacity for in vitro proliferation and their potential to differentiate into mesodermal lineages, particularly into osteoblasts. This capability has propelled their application in the fields of bone regeneration and osteochondral repair. Traditional methodologies for assessing the differentiation status of MSCs necessitate invasive procedures such as cell lysis or fixation. In this study, we introduce a nondestructive technique that utilizes an integrated label-free approach to evaluate the osteogenic maturation of MSC spheroid aggregates. This method employs scanning electrochemical microscopy (SECM) with a flexible probe in conjunction with a top-removable microfluidic device designed for easy SECM access. By tracking the production rate of p -aminophenol (PAP) in the generation/collection mode and assessing morphological changes via the negative feedback mode using [Ru(NH 3 ) 6 ]Cl 3 (Ruhex), we can discern variations in the alkaline phosphatase (ALP) activity indicative of osteogenic differentiation. This innovative strategy enables the direct evaluation of osteogenic differentiation in MSC spheroids cultured within microwell arrays without necessitating any labeling procedures. The utilization of a flexible microelectrode as the probe that scans in contact mode (with probe-substrate distances potentially as minimal as 0 μm) affords enhanced resolution compared to the traditional stiff-probe technique. Furthermore, this method is compatible with subsequent molecular biology assays, including gene expression analysis and immunofluorescence, thereby confirming the electrochemical findings and establishing the validity of this integrative approach.

Interdigitated electrodes (IDEs) enable electrochemical signal enhancement through repeated reduction and oxidation of the analyte molecule. Porosity on these electrodes is often used to lower the impedance background. However, their high capacitive current and signal interferences with oxygen reduction limit electrochemical detection ability. We present utilization of alkanethiol modification on nanoporous gold (NPG) electrodes to lower their background capacitance and chemically passivate them from interferences due to oxygen reduction, while maintaining their fast electron transfer rates, as validated by lower separation between anodic and cathodic peaks (ΔE) and lower charge transfer resistance (R ct ) values in comparison to planar gold electrodes. Redox amplification based on this modification enables sensitive detection of various small molecules, including pyocyanin, p-aminophenol, and selective detection of dopamine in the presence of ascorbic acid. Alkanethiol NPG arrays are applied as a multiplexed sensor testbed within a well plate to screen binding of various peptide receptors to the SARS COV2 S-protein by using a sandwich assay for conversion of PAPP (4-aminophenyl phosphate) to PAP (p-aminophenol), by the action of AP (alkaline phosphatase), which is validated against optical ELISA screens of the peptides. Such arrays are especially of interest in small volume analytical settings with complex samples, wherein optical methods are unsuitable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Loss-of-function mutations of the CFTR gene cause the life-shortening genetic disease cystic fibrosis (CF), whereas overactivity of CFTR may lead to secretory diarrhea and polycystic kidney disease. While effective drugs targeting the CFTR protein have been developed for the treatment of CF, little progress has been made for diseases caused by hyper-activated CFTR. Here, we solve the cryo-EM structure of CFTR in complex with CFTRinh-172 (Inh-172), a CFTR gating inhibitor with promising potency and efficacy. We find that Inh-172 binds inside the pore of CFTR, interacting with amino acid residues from transmembrane segments (TMs) 1, 6, 8, 9, and 12 through mostly hydrophobic interactions and a salt bridge. Substitution of these residues lowers the apparent affinity of Inh-172. The inhibitor-bound structure reveals re-orientations of the extracellular segment of TMs 1, 8, and 12, supporting an allosteric modulation mechanism involving post-binding conformational changes. This allosteric inhibitory mechanism readily explains our observations that pig CFTR, which preserves all the amino acid residues involved in Inh-172 binding, exhibits a much-reduced sensitivity to Inh-172 and that the apparent affinity of Inh-172 is altered by the CF drug ivacaftor (i.e., VX-770) which enhances CFTR's activity through binding to a site also comprising TM8., (© 2024. The Author(s).)

Due to the rising human population and industrialization, harmful chemical compounds such as 4-nitrophenol (4-NP) and various dyes are increasingly released into the environment, resulting in water pollution. It is essential to convert these harmful chemicals into harmless compounds to mitigate this pollution. This research focuses on synthesizing a novel heterogeneous catalyst using modified canvas fabric (CF) decorated with silver metal nanoparticles on graphene oxide nanosheets (Ag-GO/CF). The process involves coating the fabrics (CF) with graphene oxide (GO) nanosheets through sonication. Subsequently, silver nanoparticles are deposited in situ and reduced on the GO surface, resulting in the formation of the Ag-GO/CF composite. Various physicochemical characterizations were conducted to examine the interfacial interactions between CF, GO, and Ag nanoparticles. The catalytic activity of the nanocomposite was assessed by hydrogenating 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of sodium borohydride (NaBH 4 ). The results showed that the 10%Ag-5%GO/CF with a surface of 6 cm 2 (3 × 2 cm) exhibited the highest catalytic activity, achieving a reduction efficiency of over 96% in 5 min. The 4-NP reduction reaction rate was well-fitted with a pseudo-first-order kinetics model with an apparent reaction rate constant (K app ) of 0.676 min -1 . Furthermore, the Ag-GO/CF composite demonstrated remarkable stability over successive cycles, with no noticeable decrease in its catalytic activity, suggesting its promising application for long-term chemical catalytic processes. This synthesized composite can be easily added to and removed from the reaction solution while maintaining high catalytic performance in the reduction of 4-NP, and it could be beneficial in avoiding problems related to powder separation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this paper, Ti 3 C 2 QDs and Fe-ZIF-8 were synthesized by a straightforward hydrothermal method. Fe-ZIF-8 was pyrolyzed at high temperatures to obtain Fe-nanoclusters (Fe-NC). Then Fe-NC is mixed with Ti 3 C 2 QDs to form a new composite material (Ti 3 C 2 QDs/Fe-NC), and its microstructure and composition were analyzed by technology. The proposed material can detect acetaminophen (PA) and P-aminophenol (4-AP) simultaneously with excellent detection performance. With the best conditions, the linear ranges and detection limits were 0.50-210.00 μM, 0.03 μM (S/N = 3) and 0.50-150.00 μM, 0.06 μM (S/N = 3) for PA and 4-AP, respectively. The sensor has lower detection limits and wider linear ranges, and can successfully detect 4-AP and PA in river water and acetaminophen tablets at the same time, showing potential practical application prospects. Especially, this study reports the modification of MOF derivatives with Ti 3 C 2 QDs for the first time, which expands the application scope of Quantum Dots and MOF derivatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent -pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent -pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent -pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC 80 = 0.0625 μg/mL) against S. aureus compared to platensimycin.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, whereas its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed. Here, we combine molecular docking, electrophysiology, cryo-EM, and medicinal chemistry to identify CFTR modulators. We docked ∼155 million molecules into the potentiator site on CFTR, synthesized 53 test ligands, and used structure-based optimization to identify candidate modulators. This approach uncovered mid-nanomolar potentiators, as well as inhibitors, that bind to the same allosteric site. These molecules represent potential leads for the development of more effective drugs for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel drug discovery., Competing Interests: Declaration of interests B.K.S. and P.G. are founders of Epiodyne. B.K.S. is a co-founder of BlueDolphin and Deep Apple Therapeutics, as is J.J.I., and serves on the SRB of Genentech and the SABs of Vilya Therapeutics and Umbra Therapeutics and consults for Great Point Ventures and Levator Therapeutics. A patent on the discovery of positive and negative allosteric regulators for CFTR has been filed. The authors declare no other competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In our study, a series of novel 4-aminophenol benzamide-1,2,4-oxadiazole hybrid analogues have been designed and synthesized by condensing 4-hydroxyphenyl arylamides (3a-c) and 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (6a-d). The structure of the synthesised compounds was verified by various spectroscopic techniques ( 1 H NMR, 13 C NMR, IR and LC-MS). All the prepared compounds were subjected to in silico and in vitro antiproliferative study against TNBC cell lines MDA-MB-468 and MDA-MB-231. The investigations revealed that compound 7k significantly promoted apoptosis against MDA-MB-468 and MDA-MB-231 cells with IC 50 values of 22.31 µM and 26.27 µM, respectively. Compound 7k interacted with crucial active sites of MAPK and exhibited the highest docking score of -7.06 kcal/mol. Docking was validated with molecular dynamic studies with simulation for 100 ns, depicting various stable interactions with MAPK. Consequently, 7k forms stable H-Bonds and π-π stacking with amino acid residues along with π-cation. Our investigations reveal that the in vitro antiproliferative study of 7k was in good correlation with the in silico studies. Hence, 7k serves as a potential novel lead for the inhibition of TNBCs by downregulating MAPK P38.Communicated by Ramaswamy H. Sarma.

To realize the reutilization of waste Myrica rubra in the analytical field, we synthesized Myrica rubra-based N-doped carbon dots (MN-CDs) and further anchored them onto the surface of Fe 3 S 4 to fabricate Fe 3 S 4 @MN-CD nanocomposites. The as-fabricated nanocomposites possessed higher peroxidase-mimetic activity than its two precursors, resulting from the synergistic effect between them, and could catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) into deep blue oxTMB with a strong 652-nm absorption. Under optimized conditions (initial solution pH, 3.5; incubation temperature, 35 ℃; Fe 3 S 4 @MN-CD concentration, 50 µg mL -1 , and 652-nm absorption), Fe 3 S 4 @MN-CDs were employed for colorimetric assay of p-aminophenol (p-AP) with wide linear range (LR, 2.9-100 µM), low detection limit (LOD, 0.87 µM), and satisfactory recoveries (86.3-105%) in environmental waters. Encouragingly, this colorimetric assay provided the relative accuracy of 97.0-99.4% as compared with  conventional HPLC-UV detection. A portable smartphone-based colorimetric application was developed by combining the Fe 3 S 4 @MN-CD-based visually chromogenic reaction with a "Thing Identify" APP software. Besides, we engineered an image-capturing device feasible for field use, in which the internal-compact sealing prevented external light source from entering photography chamber, thereby reducing light interference, and also the bottom light source enhanced the intensity of blue imaging. This colorimetric platform exhibited satisfactory LR (1-500 µM), low LOD (0.3 µM), and fortification recoveries (86.6-99.6%). In the chromogenic reaction catalyzed by Fe 3 S 4 @MN-CDs, ·O 2 - played a key role in concomitant with the participation of •OH and h + . Both the colorimetric assay and smartphone-based intelligent sensing show great promising in on-site monitoring of p-AP under field conditions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho -aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho -aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho -amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

We present a novel bionanocatalyst fabricated by the adsorption-reduction of metal ions on a polyurethane/S-layer protein biotemplate. The bioinspired support was obtained by the adsorption of S-layer proteins (isolated from Lentilactobacillus kefiri ) on polyurethane particles. Silver and platinum nanoparticles were well-loaded on the surface of the support after the combination with metallic salts and reduction with H 2 at room temperature. Transmission electron microscopy analysis revealed the strawberry-like morphology of the bionanocatalysts with a particle size, d n , of 2.39 nm for platinum and 9.60 nm for silver. Both systems catalyzed the hydrogenation of p -nitrophenol to p -aminophenol with high efficiency in water at mild conditions in the presence of NaBH 4 . Three different amounts of bionanocatalyst were tested, and in all cases, conversions between 97 and 99% were observed. The catalysts displayed excellent recyclability over ten cycles, and no extensive damage in their nanostructure was noted after them. The bionanocatalysts were stable during their production, storage, and use, thanks to the fact that the biosupport provides an effective driving force in the formation and stabilization of the metallic nanoparticles. The successful bioinspired production strategy and the good catalytic ability of the systems are encouraging in the search for nontoxic, simple, clean, and eco-friendly procedures for the synthesis and exploitation of nanostructures.

As we work to transition the modern society that is based on non-renewable chemical feedstocks to a post-modern society built around renewable sources of energy, fuels, and chemicals, there is a need to identify the renewable resources and processes for converting them to platform chemicals. Herein, we explore a strategy for utilizing the p-hydroxybenzoate in biomass feedstocks (e. g., poplar and palm trees) and converting it into a portfolio of commodity chemicals. The targeted bio-derived product in the first processing stage is p-hydroxybenzamide produced from p-hydroxybenzoate esters found in the plant. In the second stage a continuous reaction process converts the p-hydroxybenzamide to p-aminophenol via the Hofmann rearrangement and recovers the unreacted p-hydroxybenzamide. In the third stage the p-aminophenol can be acetylated to form paracetamol, which is readily isolated by liquid/liquid extraction at >95 % purity and an overall p-hydroxybenzamide-to-paracetamol process yield of ~90 %. We explore how utilization of protecting groups alters the challenges in this process and expands the portfolio of possible products to include p-(methoxymethoxy)aniline and N-acetyl-p-(methoxymethoxy)aniline. These target compounds could become value-added renewably-sourced platform chemicals that could be used to produce biodegradable plastics, pigments, and pharmaceuticals., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Women below 40 years greatly suffer from triple negative breast cancers (TNBCs). Compared to other breast cancer cases, the poor prognosis and lower survival rate of TNBC patients make it an alarming task to save the human era from this dreadful disease. Therefore, identifying potential novel leads is urgently required to combat the TNBC. To discover a novel anticancer agent, we synthesized a series of novel 4-aminophenolbenzamide-1,3,4 oxadiazole hybrid analogues ( 7a-l). The structure of the compounds was confirmed by spectral methods (1 H & 13 C NMR, IR and MS). All the compounds were subjected to their in-silico and in-vitro antiproliferative studies against the TNBC cell lines MDA-MB-468 and MDA-MB-231. The investigations revealed that 7i has significantly promoted apoptosis against MDA-MB-468 and MDA-MB-231 cells with IC 50 values of 16.89 and 19.43 µM, respectively. Molecular docking of 7i , with MAPK has exhibited the highest binding score of -7.10 kcal/mol by interacting with crucial amino acids present at the active sites. Molecular docking is further validated with molecular dynamic studies with simulation for 100 ns, depicting various stable interactions with MAPK. Compound 7i, forms stable H-bonds and π-π stacking with amino acid residues. Molecular dynamic simulation (MDS) reveals that hydrophobic and water bridges were very prominent for 7i to bind, with the amino acid residues in close proximity to the active site of p38 MAPK. The investigations show that the In-vitro antiproliferative study of 7i agreed with the in-silico studies . Collectively, our investigations depict 7i as a potent novel lead for the inhibition of TNBCs by targeting p38 MAPK.Communicated by Ramaswamy H. Sarma.

Nitric oxide (NO) is a signaling molecule that plays a variety of functions in the human body, but it is difficult to use it in biological experiments or for therapeutic purposes because of its high reactivity and instability in the biological milieu. Consequently, photocontrollable NO releasers, which enable spatiotemporal control of NO release, have an important role in elucidating the functions of NO. Our group has developed visible-light-controllable NO-releasing molecules that contain a fluorescent dye structure as a light-harvesting antenna moiety and an N -nitrosoaminophenol structure as an NO-releasing moiety. Here, we aimed to construct an NO-generating system employing an intermolecular photoredox reaction between the two separate components, since this would simplify chemical synthesis and make it easier to examine various dyes as antennae. For this purpose, we constructed polymer nanoparticles doped with both N -methyl- N -nitroso-4-aminophenol (NAP, 1) and an Ir(III) antenna complex (2, 3 or 4) in order to dissolve in aqueous solution without a co-solvent. These polymer nanoparticles released NO upon photoirradiation in vitro in the purple (400-430 nm) or blue (400-460 nm) wavelength region to activate the doped Ir(III) complex.

We report aminophenol (A)-modified gold nanoparticles (AGNPs), which have potent antibacterial effects against multidrug-resistant bacteria with a broad antibacterial spectrum. Moreover, a series of in vitro and in vivo models indicate that AGNPs are much less ototoxic than aminoglycosides. AGNPs thus have the potential to replace aminoglycosides as novel antibacterial agents for clinical applications.

In the present study, five 4-aminophenol derivatives (4-chloro-2-(((4-hydroxyphenyl)imino)methyl)phenol(S-1), 4-((4-(dimethylamino)benzylidene)amino)phenol(S-2), 4-((3-nitrobenzylidene)amino)phenol(S-3), 4-((thiophen-2-ylmethylene)amino)phenol(S-4) and 4-((( E )-3-phenylallylidene)amino)phenol(S-5)) were synthesized and characterized by FT-IR, 1 H-NMR, 13 C-NMR and elemental analyses. The synthesized compounds were tested for their antimicrobial (Gram-positive and Gram-negative bacteria and Saccharomyces   cervesea fungus) and antidiabetic (α-amylase and α-glucosidase inhibitory) activities. All the compounds showed broad-spectrum activities against the Staphylococcus aureus (ATCC 6538), Micrococcus luteus (ATCC 4698), Staphylococcus epidermidis (ATCC 12228), Bacillus subtilis sub. sp spizizenii (ATCC 6633), Bordetella bronchiseptica (ATCC 4617) and Saccharomyces cerevisiae (ATCC 9763) strains. The newly synthesized compounds showed a significant inhibition of amylase (93.2%) and glucosidase (73.7%) in a concentration-dependent manner. Interaction studies of Human DNA with the synthesized Schiff bases were also performed. The spectral bands of S-1, S-2, S-3 and S-5 all showed hyperchromism, whereas the spectral band of S-4 showed a hypochromic effect. Moreover, the spectral bands of the S-2, S-3 and S-4 compounds were also found to exhibit a bathochromic shift (red shift). The present studies delineate broad-spectrum antimicrobial and antidiabetic activities of the synthesized compounds. Additionally, DNA interaction studies highlight the potential of synthetic compounds as anticancer agents. The DNA interaction studies, as well as the antidiabetic activities articulated by the molecular docking methods, showed the promising aspects of synthetic compounds.

In the quest for designing affordable diagnostic devices with high performance, precisely functionalized carbon-based materials with high accuracy and selectivity are required. Every material has its own unique ability to interact with the analyte, and its performance can be enhanced by probing the interaction mechanism. Herein, p -aminophenol (PAP)-functionalized reduced graphene oxide (rGO) nanoscale material is developed by a one-step synthetic route as an all-organic-based sensor. As the PAP molecules are precisely covalently interacted with the rGO at the basal plane and form a wrinkled-paper-like structure, the functionalized material exhibits an outstanding sensing ability (7.5 nM neurotransmitter dopamine (DA) at a wide linear range, 0.01-100 μM) with fast electrical transduction (<3 s) and good recyclability (∼10 cycles) in a real sample. Combining various analytical and density functional theory (DFT) calculation methods, physicochemical properties and the interaction mechanism of analyte-materials transduction are discussed exclusively. Besides, the potential application of the well-dispersed rGO-PAP gravure ink in flexible-printed electronics fields is explored. This study not only provides new insights into the surface/interface chemistry and working principle of this unique anchoring of PAP on rGO but also offers a new pathway for developing other forms of metal-free/organic functionalized biosensors with high efficiency.

The catalytic reduction reaction is one of the most commonly used solutions to convert high-risk contaminants into safe or low-risk materials. Today, with the increasing water pollution, the urgent need for efficient and effective catalysts is felt more than ever. For this purpose, for the first time, a green catalyst composed of silver nanoparticles anchored on itaconic acid-modified Ca-Al layered double hydroxide/gellan gum nanocomposite (Ag/LDH-ITA-GG NC) was prepared from a green approach without the use of any toxic organic solvents. To gain an in-depth insight into the physicochemical properties of the catalyst, different techniques including nitrogen adsorption-desorption isotherms, FESEM/mapping, FTIR, TGA, and XRD were used. The catalytic performance of the Ag/LDH-ITA-GG NC toward 4-nitrophenol reduction by NaBH 4 was investigated. The calculated values of the apparent rate constant for this reaction are 0.2142 min -1 (for 1.0 mg of the catalyst), 0.2375 min -1 (for 3.0 mg of the catalyst), and 0.2550 min -1 (for 5.0 mg of the catalyst), indicating that the catalytic conversion of 4-nitrophenol to 4-aminophenol on the Ag/LDH-ITA-GG NC catalyst follows the pseudo-first-order kinetics and is comparable to the previous findings in the literature. The results of this study indicated that Ag/LDH-ITA-GG NC can potentially be utilized as an auspicious high efficient green catalyst for the reduction of pollutants like 4-nitrophenol., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mo 5 N 6 nanosheets were synthesized by a nickel-induced growth method and were found to possess peroxidase-like activity in acidic condition and catalase-like activity in weak basic condition. In acidic condition, Mo 5 N 6 nanosheets can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H 2 O 2 to form a blue color product (TMB OX ). At the co-existence of 4-aminophenol (4-AP), 4-AP can react with H 2 O 2 and TMB OX , resulting in the decrease of TMB OX and the fading of blue color. Therefore, a facile, sensitive colorimetric method for the quantitative detection of 4-AP was developed. The linear range for 4-AP was 1.0 to 80.0 μmol⋅L ‒1 (R 2  = 0.999), and the detection limit was 0.56 μmol⋅L ‒1 based on 3σ/k. Resorcinol, aniline, humic acid, and common ions and anions in surface water did not interfere the determination of 4-AP. This colorimetric method was applied to measure the 4-AP in real water sample from Wulong River in Fujian Province of China. The relative standard deviation for the determination of 4-AP was ranged from 0.03 to 1.88%, and the recoveries from spiked samples were ranged between 99.2 and 107.6%. The determination results were consistent with those obtained by HPLC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

ZnSe nanodisks:Ti 3 C 2 MXene complex was prepared for the first time. Based on its remarkable photoelectrochemical performance, combined with the enzyme-free toehold-mediated strand displacement reaction, a photoelectrochemical biosensor for the detection of the non-small-cell cancer biomarker ctDNA KRAS G12D was developed. ZnSe nanodisks were in situ grown on Ti 3 C 2 MXene surface by two-step hydrothermal method. The high conductivity and adjustable band gap of MXene significantly enhanced the photoelectric response of ZnSe. Subsequently, the photoelectrochemical biosensor was prepared by combining with the signal amplification function of p-aminophenol and the enzyme-free toehold-mediated strand displacement reaction on the modified ITO electrode surface. Under the optimized conditions, the linear detection range is 0.5 ~ 100.0 fM, and the detection limit is 0.2 fM, which realizes the sensitive detection of KRAS G12D. The photoelectrochemical biosensor constructed opens up a new pathway for the preparation of new Mxene-based composite materials and the research of photoelectrochemical biosensor. Nucleic acid liquid biopsy with ZnSe nanodisks:Ti 3 C 2 MXene photoelectroactive modified electrode., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Bimetallic nanoparticles (BNPs) constitute two different metal elements and exhibit relatively superior mechanistic and catalytic efficacies owing to their synergistic functions over monometallic nanoparticles. In the present study various bimetallic Ag-Au, Ag-Pd, Au-Pd nanoparticles were synthesized using a natural biopolymer gum kondagogu (GK) as a reducing and capping agent, by a simple and cost-effective method. The synthesized BNPs when characterized using UV-vis spectroscopy revealed a specific surface plasmon resonance band (SPR) of each nanocomposite. The average particle size of Ag-Au, Ag-Pd, and Au-Pd BNPs was found to be 23 ± 10.3, 21 ± 7.6, and 23 ± 9.4 nm respectively based on transmission electron microscopy analysis. Surface morphology and functional groups on the gum matrix of GK-BNPs were analyzed by XRD and FT-IR respectively. The bimetallic nanocomposites were evaluated for their catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol in the presence of NaBH 4 . The kinetic studies performed, depicted rate constants for Ag-Au, Ag-Pd, and Au-PdNPs as 0.31, 0.39, and 0.28 min -1 respectively. The catalytic efficiencies of three bimetallic nanocomposites were of the following order Ag-Pd > Ag-Au > Au-Pd. This study establishes the catalytic potentials of the three different bimetallic nanocomposites in the reduction of 4-NP an environmental pollutant, and the impact of their synergistic property., (Copyright © 2021 Elsevier B.V. All rights reserved.)

α,β-Unsaturated carbonyls are reactive group often found in bioactive small molecules. Their non-specific reaction with biomolecules can be the cause of the low efficacy and unexpected side-effects of the molecule. Accordingly, unprotected α,β-unsaturated carbonyls are not often found in drugs. Here, we report that o-aminophenol is a new masking group of α,β-unsaturated ketone, which is inspired by natural products saccharothriolides. o-Aminophenol adduct of α,β-unsaturated ketone, but not those of α,β-unsaturated amide or ester, undergoes a retro-Michael reaction to yield o-aminophenol and the Michael acceptor. This reaction was observed only in protic solvents, such as MeOH and aqueous MeOH. In contrast, o-anisidine was not eliminated from its Michael adduct. o-Aminophenol may be a promising masking tool of highly-reactive bioactive α,β-unsaturated carbonyl compounds., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Unlike the closely related and widely investigated amidino-substituted benzimidazoles and benzothiazoles with a range of demonstrated biological activities, the matching benzoxazole analogues still remain a largely understudied and not systematically evaluated class of compounds. To address this challenge, we utilized the Pinner reaction to convert isomeric cyano-substituted 2-aminophenols into their amidine derivatives, which were isolated as hydrochlorides and/or zwitterions, and whose structure was confirmed by single crystal X-ray diffraction. The key step during the Pinner synthesis of the crucial carboximidate intermediates was characterized through mechanistic DFT calculations, with the obtained kinetic and thermodynamic parameters indicating full agreement with the experimental observations. The obtained amidines were subjected to a condensation reaction with aryl carboxylic acids that allowed the synthesis of a new library of 5- and 6-amidino substituted 2-arylbenzoxazoles. Their antiproliferative features against four human tumour cell lines (SW620, HepG2, CFPAC-1, HeLa) revealed sub-micromolar activities on SW620 for several cyclic amidino 2-naphthyl benzoxazoles, thus demonstrating the usefulness of the proposed synthetic strategy and promoting amidino substituted 2-aminophenols as important building blocks towards biologically active systems.

Natural product congeners serve a useful role in the understanding of natural product biosynthesis and structure-activity relationships. A minor congener with superior activity, selectivity, and modifiable functional groups could serve as a more effective lead structure and replace even the original lead molecule that was used for medicinal chemistry modifications. Currently, no effective method exists to discover targeted congeners rapidly, specifically, and selectively from producing sources. Herein, a new method based on liquid-chromatography tandem-mass spectrometry combination is evaluated for targeted discovery of congeners of platensimycin and platencin from the extracts of Streptomyces platensis . By utilizing a precursor-ion searching protocol, tandem mass spectrometry not only confirmed the presence of known congeners but also provided unambiguous detection of many previously unknown congeners of platensimycin and platencin. This high-throughput and quantitative method can be rapidly and broadly applied for dereplication and congener discovery from a variety of producing sources, even when the targeted compounds are obscured by the presence of unrelated natural products.

Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Cystic fibrosis (CF) is the most frequent life-limiting autosomal recessive disorder in the Caucasian population. It is due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Current symptomatic CF therapies, which treat the downstream consequences of CFTR mutations, have increased survival. Better knowledge of the CFTR protein has enabled pharmacologic therapy aiming to restore mutated CFTR expression and function. These CFTR "modulators" have revolutionised the CF therapeutic landscape, with the potential to transform prognosis for a considerable number of patients. This review provides a brief summary of their mechanism of action and presents a thorough review of the results obtained from clinical trials of CFTR modulators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

In this study, dense gold-assembled SiO 2 nanostructure (SiO 2 @Au) was successfully developed using the Au seed-mediated growth. First, SiO 2 (150 nm) was prepared, modified by amino groups, and incubated by gold nanoparticles (ca. 3 nm Au metal nanoparticles (NPs)) to immobilize Au NPs to SiO 2 surface. Then, Au NPs were grown on the prepared SiO 2 @Au seed by reducing chloroauric acid (HAuCl 4) by ascorbic acid (AA) in the presence of polyvinylpyrrolidone (PVP). The presence of bigger (ca. 20 nm) Au NPs on the SiO 2 surface was confirmed by transmittance electronic microscopy (TEM) images, color changes to dark blue, and UV-vis spectra broadening in the range of 450 to 750 nm. The SiO 2 @Au nanostructure showed several advantages compared to the hydrofluoric acid (HF)-treated SiO 2 @Au, such as easy separation, surface modification stability by 11-mercaptopundecanoic acid (R-COOH), 11-mercapto-1-undecanol (R-OH), and 1-undecanethiol (R-CH 3 ), and a better peroxidase-like catalysis activity for 5,5'-Tetramethylbenzidine (TMB) and hydrogen peroxide (H 2 O 2 ) reaction. The catalytic activity of SiO 2 @Au was two times better than that of HF-treated SiO 2 @Au. When SiO 2 @Au nanostructure was used as a surface enhanced Raman scattering (SERS) substrate, the signal of 4-aminophenol (4-ATP) on the surface of SiO 2 @Au was also stronger than that of HF-treated SiO 2 @Au. This study provides a potential method for nanoparticle preparation which can be replaced for Au NPs in further research and development.

Silver nanoparticles (AgNPs) are widely sought after for a variety of biomedical and environmental applications due to their antimicrobial and catalytic properties. We present here a green and simple synthesis of AgNPs utilizing traditional Chinese medicinal herbs. The screening of 20 aqueous herb extracts shows that Sheng Di Huang (Rehmannia glutinosa) had the most promising potential in producing AgNPs of 30±6 nm, with narrow size distribution and high crystallinity. The antimicrobial activities of these AgNPs conducted on E. coli cells were found to be superior in comparison to poly(vinylpyrrolidone)-capped AgNPs synthesized using common chemical method. Additionally, the AgNPs obtained possess excellent catalytic performance in the reduction of 4-nitrophenol to 4-aminophenol. We compared the phytochemical and FTIR spectral analyses of the herb extract before and after synthesis, in order to elucidate the phytochemicals responsible for the reduction of Ag + ions and the capping of the AgNPs produced., (© 2020 Wiley-VCH GmbH.)

Using the GUSAR 2013 program, the quantitative structure-antioxidant activity relationship has been studied for 74 phenols, aminophenols, aromatic amines and uracils having lgk 7 = 0.01-6.65 (where k 7 is the rate constant for the reaction of antioxidants with peroxyl radicals generated upon oxidation). Based on the atomic descriptors (Quantitative Neighborhood of Atoms (QNA) and Multilevel Neighborhoods of Atoms (MNA)) and molecular (topological length, topological volume and lipophilicity) descriptors, we have developed 9 statistically significant QSAR consensus models that demonstrate high accuracy in predicting the lgk 7 values for the compounds of training sets and appropriately predict lgk 7 for the test samples. Moderate predictive power of these models is demonstrated using metrics of two categories: (1) based on the determination coefficients R 2 (R 2 TSi , R 2 0 , Q 2 ( F1 ), Q 2 ( F2 ), RmTSi2¯) and based on the concordance correlation coefficient (CCC)); or (2) based on the prediction lgk 7 errors (root mean square error (RMSEP), mean absolute error (MAE) and standard deviation (S.D.)) The RBF-SCR method has been used for selecting the descriptors. Our theoretical prognosis of the lgk 7 for 8-PPDA, a known antioxidant, based on the consensus models well agrees with the experimental value measure in the present work. Thus, the algorithms for calculating the descriptors implemented in the GUSAR 2013 program allow simulating kinetic parameters of the reactions underling the liquid-phase oxidation of hydrocarbons.

The analysis of cannabis plant material submitted to seized-drug laboratories was significantly affected by the signing of the Agricultural Improvement Act of 2018, which defined hemp and removed it from the definition of marijuana in the Controlled Substances Act. As a result, field law enforcement personnel and forensic laboratories now are in need of implementing new protocols that can distinguish between marijuana-type and hemp-type cannabis. Colorimetric tests provide a cost-effective and efficient manner to presumptively identify materials prior to submission to a laboratory for analysis. This work presents the validation of the 4-aminophenol (4-AP) color test and demonstrates its utility for discriminating between marijuana-type and hemp-type cannabis (i.e., typification). Validation studies included the testing of numerous cannabinoid reference materials, household herbs, previously characterized cannabis plant samples, and real-case samples. The 4-AP test reliably produces a pink result when the level of Δ 9 -tetrahydrocannabinol (THC) is approximately three times lower than the level of cannabidiol (CBD). A blue result is generated when the level of THC is approximately three times higher than that of CBD. Inconclusive results are observed when the levels of THC and CBD are within a factor of three from each other, demonstrating the limitations of the test under those scenarios., (© 2020 American Academy of Forensic Sciences.)

Herein, a simple method is used for fabrication of carbon nitride (g-C 3 N 4 ) incorporated sodium alginate (Alg) beads. The alginate carbon nitride beads (Alg-CNBs) were prepared by introducing the g-C 3 N 4 dispersed Alg aqueous solution to a divalent Ca 2+ ions solution. Alg-CNBs were further treated with different transition metal salt solutions. The surface coated transition metal ions on Alg-CNBs were reduced to zero-valent state (M 0 ), through strong reducing agent NaBH 4 , and used for the catalytic reduction of different organic dyes. The surface morphology of all catalysts was investigated by FE-SEM and metal uptake capacity was investigated by ICP-OES. The prepared M 0 /Alg-CNBs (where M 0  = Ag 0 , Ni 0 , Fe 0 and Cu 0 ) catalysts were tested against the reduction of 4-nitrophenol (4-NP) to recognize the fastest one. Among all the catalysts, the Cu 0 /Alg-CNBs efficiently reduced 4-NP to 4-aminophenol (4-AP). Cu 0 /Alg-CNBs was used further for the reduction of methyl orange (MO), congo red (CR), 2-nitrophenol (2-NP) and 2,6-dinitrophenol (2,6-DNP). The MO, CR and 4-NP was reduced with rate constant of 0.135, 0.077 and 0.384 min -1 , respectively. For large scale and continuous reduction of 4-NP to 4-AP, the column was packed with 0.15 g catalyst and the reducible reactants were passed through it. A reduction of 4-NP up to 97-99% was achieved by simply passing it through column packed with catalyst under gravity. Similarly, effects of changing initial dye concentration, catalytic dosage and NaBH 4 performance has been investigated for the reduction process. Also, the prepared catalyst beads can be easily prepared, recovered simply by discarding the dye after completion of the reaction, recyclable and its good catalytic activity., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, the cytotoxic behavior of six ruthenium(II) complexes of stoichiometry [(η 6 - p -cymene)RuCl 2 L] (I-VI), L = 4-cyanopyridine (I), 2-aminophenol (II), 4-aminophenol (III), pyridazine (IV), and [( η 6 - p -cymene)RuClL 2 ]PF 6 ; L = cyanopyridine (V), L = 2-aminophenol(VI) towards three cell lines was studied. Two of them, HeLa and MCF-7, are human carcinogenic cells from cervical carcinoma and human breast cancer, respectively. A comparison with healthy cells was carried out with BGM cells which are monkey epithelial cells of renal origin. The behavior of complex II exhibits selectivity towards healthy cells, which is a promising feature for use in cancer treatment since it might reduce the side effects of most current therapies.

Although the 1,2,3-triazole is a commonly used amide bioisostere in medicinal chemistry, the structural implications of this replacement have not been fully studied. Employing X-ray crystallography and computational studies, we report the spatial and electronic consequences of replacing an amide with the triazole in analogues of cystic fibrosis drugs in the VX-770 and VX-809 series. Crystallographic analyses quantify subtle differences in the relative positions and conformational preferences of the R 1 and R 2 substituents attached to the amide and triazole bioisosteres. Computational studies derived from the X-ray data highlight the improved hydrogen bonding donor and acceptor capabilities of the amide in comparison to the triazole. This analysis of the spatial and electronic differences between the amide and 1,2,3-triazole will inform medicinal chemists as they consider using the triazole as an amide bioisostere., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa . The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between " D × ρ tapped " and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

Plant hormones (PHs) are a type of pesticide that can potentially affect human health. Therefore, their quantitative detection is particularly important. In this study, a green and economic method for the simultaneous extraction and determination of four PHs, namely thidiazuron, forchlorfenuron, 1-naphthylacetic acid, and 2-naphthoxyacetic acid, in watermelon juice was developed by using m-aminophenol-urea-glyoxal resin as the adsorbent for pipette tip solid phase extraction (PT-SPE) coupled with liquid chromatography. The resin was synthesized via a simple (one pot hydrothermal synthesis) and green (ethanol as the solvent and glyoxal as crosslinking agent) process. The synthesized resin possesses multiple functional groups (hydroxyl, amino, and imino, among others), high adsorption capacity, larger specific surface area than the urea-glyoxal resin and m-aminophenol-glyoxal resin, and can be regenerated easily. The PT-SPE device is simple, cheap, and easy to obtain, and the adsorbent dosage is only 5.0 mg. The proposed method has a wide linear detection range, high recovery, good precision, and high sensitivity, and satisfies the measurement requirements for detecting trace levels of PHs in fruits and vegetables., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this work was to investigate on the possibility to use nano-magnetite particles supported on waste biomass as heterogeneous catalyst for the production of p-aminophenol starting from a well-known pollutant, p-nitrophenol, in fixed-bed reactors. The kinetic and the thermodynamic of the process was firstly studied in batch system, subsequently a first scale-up was performed using a glass column packed with the supported catalyst. The experimental data obtained with the column were interpreted in light of a suitable dynamic model. The Langmuir-Hinshelwood mechanism well described the process, obtaining from the data fitting a surface rate kinetic constant k = 2.68 × 10 -6  mol/m 2· h, an adsorption equilibrium constants for PNP and BH 4 - species equal to 20.07 l/mol and 1.83 l/mol, at 25 °C. The Eyring equation was used to fit the apparent kintic constant variation with the temperature, to estimate thermodynamic parameters, obtaining a ΔH = - 1145.68 kJ/mol and ΔS = -315.02 kJ/K·mol. The process was then simulated in PROII environment, investigating the influence of initial PNP flowrate, NaBH 4 /PNP and reactor length/diameter ratios on PNP conversion, on required duty to maintain isothermal conditions and on pressure drops in the reactor., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function.

The aggregation of zinc oxide nanoparticles leads to an increased absorbance in the ultraviolet-visible region by an induced light scattering effect. Herein, we demonstrate the inhibition of photoconversion activity in ZnO-graphene core-shell quantum dots (QD) (ZGQDs) agglomerated by 4-aminophenol (4-AP) used as a linker. The ZnO-graphene quantum dots (QD) aggregates (ZGAs) were synthesized using a facile solvothermal process. The ZGAs revealed an increased absorbance in the wavelengths between 350 and 750 nm as compared with the ZGQDs. Against expectation, the calculated average photoluminescence lifetime of ZGAs was 7.37 ns, which was 4.65 ns longer than that of ZGQDs and was mainly due to the high contribution of a slow (τ 2 , τ 3 ) component by trapped carriers in the functional groups of graphene shells and 4-AP. The photoelectrochemical (PEC) cells and photodetectors (PDs) were fabricated to investigate the influence of ZGAs on the photoconversion activity. The photocurrent density of PEC cells with ZGAs was obtained as 0.04 mA/cm 2 at 0.6 V, which was approximately 3.25 times lower than that of the ZGQDs. The rate constant value of the photodegradation value of rhodamine B was also decreased by around 1.4 times. Furthermore, the photoresponsivity of the PDs with ZGAs (1.54 μA·mW -1 ) was about 2.5 times as low as that of the PDs with ZGQDs (3.85 μA·mW -1 ). Consequently, it suggests that the device performances could be degraded by the inhibition phenomenon of the photoconversion activity in the ZGAs due to an increase of trap sites.

The cation-independent mannose-6-phosphate receptor (CI-M6PR, aka insulin-like growth factor II receptor or IGFIIR) is a membrane protein that plays a central role in the trafficking of lysosomal acid hydrolases into lysosomes via mannose-6-phosphate (M6P) binding domains. In order to maintain cellular metabolic/catabolic homeostasis, newly synthesized lysosomal acid hydrolases are required to bind to M6PR for transit. Acid hydrolases secreted by cells can also be internalized via M6PR residing on the cell membrane and are transported to the lysosomes, a feature that enables enzyme replacement therapy for the treatment of several lysosomal storage disorders. Therefore, a thorough characterization of this receptor is critical to the development of lysosomal enzyme-based therapeutics that utilize M6PR for drug delivery to the lysosome. However, the extracellular domain (ECD) of M6PR is highly complex, containing 15-mannose receptor homology (MRH) domains. In addition, homodimerization of the receptor can occur at the membrane, making its characterization challenging. In this study, a novel human M6PR (hM6PR)-overexpressing cell line originally established for hM6PR cellular uptake assay was utilized for production of hM6PR-ECD, and a novel small molecule biomimetic (aminophenyl-M6P) affinity resin was developed for the purification of M6PR-ECD. The affinity-purified hM6PR-ECD was monomeric, contained 14 intact MRH domains (1-14) and a partial MRH domain 15, and was successfully employed in ELISA-based and surface plasmon resonance-based binding assays to demonstrate its ligand-binding functionality, making it suitable for the evaluation of biotherapeutics that utilize M6PR for cellular internalization., Competing Interests: Declaration of competing interest All authors are or were Takeda Pharmaceutical employees at the time of this study., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In this paper the innovative approach of nano into micro dry powders (NiM) was applied to incorporate into mannitol or mannitol/cysteamine micromatrices ivacaftor-loaded nanoparticles for pulmonary delivery in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing loaded with ivacaftor at 15.5% w/w were produced. The nanoparticles were incorporated into microparticles to obtain NiM that were fully characterized in terms of size, morphology, interactions with artificial Cf mucus (CF-AM) as well as for aerodynamic behaviour. Finally the activity of ivacaftor-containing NiM was evaluated by in vitro preliminary experiments. NiM at matrix composed by a mixture of mannitol:cysteamine showed greater ability to reduce CF-AM viscosity whereas that based on just mannitol showed better aerodynamic properties with a FPF of about 25%. All produced NiM showed very good cytocompatibility and the released ivacaftor was able to restore the chroride transport in vitro., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)