Integration of Myrica rubra-based N-doped carbon dots with Fe3S4 as excellent peroxidase mimics for colorimetric assay and smartphone-based intelligent sensing of p-aminophenol in waters.

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 Fe3S4 to fabricate Fe3S4@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 ℃; Fe3S4@MN-CD concentration, 50 µg mL-1, and 652-nm absorption), Fe3S4@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 Fe3S4@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 Fe3S4@MN-CDs, ·O2- 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.

State-of-art advances on removal, degradation and electrochemical monitoring of 4-aminophenol pollutants in real samples: A review.

p_Aminophenol, namely 4-aminophenol (4-AP), is an aromatic compound including hydroxyl and amino groups contiguous together on the benzene ring, which are suitable chemically reactive, amphoteric, and alleviating agents in nature. Amino phenols are appropriate precursors for synthesizing oxazoles and oxazines. However, since the toxicity of aniline and phenol can harm human and herbal organs, it is essential to improve a reliable technique for the determination of even a trace amount of amino phenols, as well as elimination or (bio)degradation/photodegradation of it to protect both the environment and people's health. For this purpose, various analytical methods have been suggested up till now, including spectrophotometry, liquid chromatography, spectrofluorometric and capillary electrophoresis, etc. However, some drawbacks such as the requirement of complex instruments, high costs, not being portable, slow response time, low sensitivity, etc. prevent them to be employed in a wide range and swift in-situ applications. In this regard, besides the efforts such as (bio)degradation/photodegradation or removal of 4-AP pollutants from real samples, electroanalytical techniques have become a promising alternative for monitoring them with high sensitivity. In this review, it was aimed to emphasize and summarize the recent advances, challenges, and opportunities for removal, degradation, and electrochemical sensing 4-AP in real samples. Electroanalytical monitoring of amino phenols was reviewed in detail and explored the various types of electrochemical sensors applied for detecting and monitoring in real samples. Furthermore, the various technique of removal and degradation of 4-AP in industrial and urban wastes were also deliberated. Moreover, deep criticism of multifunctional nanomaterials to be utilized as a catalyst, adsorbent/biosorbent, and electroactive material for the fabrication of electrochemical sensors was covered along with their unique properties. Future perspectives and conclusions were also criticized to pave the way for further studies in the field of application of up-and-coming nanostructures in environmental applications.

Quantitative Determination of Anti-Migraine Quaternary Mixture in Presence of p-Aminophenol and 4-Chloroacetanilide.

A validated RP-HPLC method was developed for the estimation of paracetamol, caffeine, metoclopramide and ergotamine simultaneously in bulk and pharmaceutical formulation. The method was extended for the determination of two paracetamol genotoxic and nephrotoxic impurities and degradation products namely p-aminophenol and 4-chloroacetanilide. Separation was done on octadecyl column (15 cm × 2.1 mm, 5 µm). Gradient elution was performed using mobile phase consisting of acetonitrile and water (pH 3) in ratio of (20: 80, v/v) for the first 3 min, (50: 50, v/v) for the next 4.5 min, then (20: 80, v/v) for the final 2.5 min. The flow rate was 0.7 mL/min throughout the run which took 10 min. UV detection was done at 230 nm. The proposed method agreed with ICH guidelines of method validation. The suggested method was applied for the estimation of the proposed drugs in their dosage form. Statistical comparison was done between the results obtained from the suggested method and those obtained from reported HPLC method. The proposed method is more beneficial than the published one because of having higher sensitivity and selectivity as it allows the detection of the proposed drugs in lower concentrations in the presence of paracetamol toxic impurities, p-aminophenol and 4-chloroacetanilide.

Salt-template preparation of Mo5N6 nanosheets with peroxidase- and catalase-like activities and application for colorimetric determination of 4-aminophenol.

Mo5N6 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, Mo5N6 nanosheets can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to form a blue color product (TMBOX). At the co-existence of 4-aminophenol (4-AP), 4-AP can react with H2O2 and TMBOX, resulting in the decrease of TMBOX 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 (R2 = 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.

Amperometric determination of ecotoxic N-methyl-p-aminophenol sulfate in photographic solution and river water samples based on graphene oxide/CeNbO4 nanocomposite catalyst.

The electronic conductivity of the metal oxides is generally increased by hybridization of highly conductive carbon supportive materials. In this present work, we have demonstrated a novel one-pot preparation of cerium niobate (CeNbO4) nanoparticles embedded with graphene oxide (GO/CeNbO4) composite, for ultrasensitive detection of the photographic developing agent, metol (MTL). The as-prepared GO/CeNbO4 was analyzed by various characterization techniques. The intensive characterization techniques were used to affirm the detailed structural moiety, size, morphology, and surface area of GO/CeNbO4. The GO/CeNbO4 modified glassy carbon electrode (GCE) affords a superior electrocatalytic activity toward MTL. The obtained amperometric response on the GO/CeNbO4/GCE holding an extremely low level detection of 10 nM and superior sensitivity of 10.97 µA µM-1 cm-2 toward MTL detection. Besides, the GO/CeNbO4/GCE also gives excellent selectivity, stability, repeatability, and reproducibility. We achieved excellent recovery results in real photographic solution and river water samples analysis with great accuracy. This work offers a novel insight into the growth of the carbon-based niobate family with electrochemical sensor applications.

Calibration curve-free electrochemical quantitation by micro-nano multi-scale gap devices.

Quantitation without relying on the calibration curve has long been an issue of overcoming analytical problems accompanied with the inherent limitations of the calibration curve fitting errors. Here, we report on a calibration curve-free method for electrochemical quantitation based on a multi-scale gap device (MGD). The MGD is an integrated device having a series of interdigitated electrodes (IDE) with micro-to-nano gap distances. The device shows a gap-dependent redox current of the analyte when subjected to the electrochemical cycling between the two facing electrodes of its componential IDEs. Based on the fact that the current increases as the gap distance decreases, the analyte concentration could be directly estimated: the rate of increase in the current was directly proportional to the analyte concentration. The calibration curve was not necessary for the quantitation. The accuracy of this MGD approach was better than that of an IDE collection of the same gap distance, which was deteriorated at the larger gap distances particularly. The MGD-based quantitation of dopamine, potassium ferricyanide, and aminophenol was demonstrated in a relatively broad range of concentrations (100 nM-5 mM).

Rapid synthesis of a hybrid of rGO/AuNPs/MWCNTs for sensitive sensing of 4-aminophenol and acetaminophen simultaneously.

In this work, a hybrid of multiwalled carbon nanotubes, nanogold, and reduced graphene (rGO/AuNPs/MWCNTs) was synthesized rapidly with an easy method, and then combined with chitosan (CS), which was fixed on a glassy carbon electrode (GCE) to construct a new kind of electrochemical sensor to simultaneously determine 4-aminophenol (4-AP) and acetaminophen (AC). When detecting 4-AP and AC simultaneously, the linear range is 0.12~12 µM for acetaminophen and 0.05~25 µM for 4-aminophenol; the detection limit is 42 nM for acetaminophen and 2.95 nM for 4-aminophenol. Compared with previously related reports, the proposed sensor has an excellent electrocatalytic performance for the redox of 4-AP and AC, which can effectively determine 4-AP and AC simultaneously in actual samples and has potential application prospect. Graphical abstract.

Simultaneous Determination of Paracetamol, Propyphenazone and Caffeine in Presence of Paracetamol Impurities Using Dual-Mode Gradient HPLC and TLC Densitometry Methods.

Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A "dual-mode" gradient high-performance liquid chromatography method was developed, where the separation was achieved via "dual-mode" gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 µm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.

Simulated kinetics of the atmospheric removal of aniline during daytime.

Oxidations of aniline (AN) initiated by OH-radicals are simulated in the temperature range 200-400 K using DFT/M06-2X/6-311++G(2df,2p) and ab initio ROCBS-QB3 levels. Chemical kinetics of such reactions were investigated based on several approaches including classical transition state theory (TST), conical variational transition state theory (CVT), and Rice-Ramsperger-Kassel-Marcus master equation (RRKM-ME) theories. Under atmospheric conditions, the reaction of OH radical with AN and the subsequent reactions with O2 molecules are investigated. The results indicate that the majority of O2 addition goes to the anti-directions with a branching ratio of 97.7% and produces the bicyclic peroxy radicals (BPRs) that can react with NO radical to form bicyclic alkoxy radicals (BARs). The latter compounds can be stabilized either by cyclization or via ring cleavage.

A comparative study of two novel validated spectrophotometric techniques for resolution of four-component mixtures with severely overlapping spectra.

Two new smart spectrophotometric methods are developed and validated for the determination of the quatertnary mixture of paracetamol (acetaminophen), diphenhydramine, p-aminophenol, and N-oxide degradate of diphenhydramine. Method A is the novel triple divisor ratio difference method, where the triple divisor ratio spectrum of the component of interest shows a significant amplitude difference at two selected wavelengths where the three interfering substances are used as triple divisor and give constant amplitude all over the spectrum. The triple divisors are normalized spectra of tertiary mixtures containing 40 µg/mL of each of the 3 interfering components. The selected wavelengths are 256-290 nm, 220-230 nm, 230-245 nm and 275-260 nm for the 4 components, respectively. Method B is double divisor - ratio difference-dual wavelength, where the double divisor ratio spectrum of the component of interest shows a significant amplitude difference at two selected wavelengths where two interfering substances are used as double divisor and give constant amplitude all over the spectrum, while the third one shows zero amplitude difference at these two selected wavelengths. The double divisors used are normalized spectra of diphenhydramine /N-oxide degradate of diphenhydramine binary mixture for both paracetamol and p-aminophenol and paracetamol/p-aminophenol binary mixture for both diphenhydramine hydrochloride and its N-oxide degradate. The double divisors binary mixtures contain 40 µg/mL of each component. The selected wavelengths are 243-233 nm, 223.8-270.2 nm, 237-250 nm and 265-234.6 nm for the 4 compounds, respectively. Both methods were successfully applied for the quantification of the four components in laboratory prepared quaternary mixtures and for the quantification of paracetamol and diphenhydramine hydrochloride in panadol night® tablets. The results obtained by the developed methods were compared with those obtained by the United State Pharmacopeial method for the analysis of paracetamol and diphenhydramine, where no significant differences were found.

Assessment of p-aminophenol oxidation by simulating the process of hair dyeing and occurrence in hair salon wastewater and drinking water from treatment plant.

This work reports the study of oxidation reaction of p-aminophenol (PAP) in ammoniacal medium in dissolved atmospheric oxygen and hydrogen peroxide, simulating the process of hair dyeing with permanent dyes. The products formed, which included semi-quinoneimine radical, quinoneimine, dimers, trimers and tetramers, were identified by mass spectrometry, infrared spectroscopy, UV-vis spectrophotometry, and nuclear magnetic resonance of hydrogen. The process was found to involve an autoxidation mechanism. The mutagenicity of the products was carried out by Salmonella Typhimurium YG1041 assay, and the results indicated no mutagenic properties. The presence of PAP and its oxidative products in samples of wastewater collected from hairdressing salon effluent (WW), raw river water (RRW), and water inlet and outlet of drinking water treatment plant (DWTP) was analyzed by HPLC-DAD. PAP was detected in the collected samples of WW, water samples from DWTP (before and after treatment), at concentrations of 2.1 ± 0.5 mg L-1, 1.9 ± 0.3 × 10-3 mg L-1 and 1.3 ± 0.2 × 10-3 mg L-1, respectively. The reaction products, including dimers, trimers and tetramers were identified only in the WW sample; this shows that both the precursor in the sample and its derivatives were released into the wastewater.

A sensitive sensor based on MOFs derived nanoporous carbons for electrochemical detection of 4-aminophenol.

A novel electrochemical sensor based on zinc oxide/nitrogen doped porous carbons (ZnO/NPC) modified electrode has been constructed for detecting 4-aminophenol (4-AP). The ZnO/NPC material was synthesized by one-step carbonization of MOF-5-NH2. The modified glassy carbon electrode (ZnO/NPC/GCE) holds excellent electrocatalytic activity toward 4-AP, with a sensitivity of about 31.02 µA/µM/cm2. Under optimal conditions, its oxidation peak current increases linearly with the increasing concentration of 4-AP (from 5 to 120 µmol/L), and the detection limits is 0.014 µmol/L (S/N = 3). Furthermore, favorable selectivity, superior reproducibility and outstanding stability have been achieved. The ZnO/NPC/GCE has been applied in detecting 4-AP in industrial waste water and achieved positive results with the recovery of 4-AP ranging from 94.02% to 107.7%, which confirms that this sensor is a reliable platform for the detection of 4-AP in waste water.

Development and Validation of a Novel Stability-Indicating RP-HPLC Method for Simultaneous Determination of Tezacaftor and Ivacaftor in Fixed Dose Combination.

A simple and precise novel stability-indicating method for the simultaneous estimation of tezacaftor and ivacaftor in combined tablet dosage form was developed and validated using reversed-phase high-performance liquid chromatography (RP-HPLC). The method is being reported for the first time and includes an estimation of degradation products produced post-stress conditions without any extraction or derivatization. The chromatographic separation of the drugs was achieved with a Symmetry Shield RP18 Column (100 Å, 5 µm, 4.6 mm × 250 mm) using a mixture of buffer, methanol and acetonitrile (42:27:31 v/v/v) as mobile phase. The buffer used in mobile phase contained 35 mM potassium dihydrogen phosphate, and its pH was adjusted to 7.0 ± 0.02 with 20% orthophosphoric acid. The instrument was set at flow rate of 1.2 mL min-1 at ambient temperature and the wavelength of UV-visible detector at 275 nm. The developed method could be suitable for the quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. Stress testing was performed to prove the specificity. No interference was observed from its stress degradation products. The statistical analysis was done by using F-test and t-test at 95% confidence level.

Development and Validation of Chromatographic Methods for Simultaneous Determination of Paracetamol, Orphenadrine Citrate and Caffeine in Presence of P-aminophenol; Quantification of P-aminophenol Nephrotoxic Impurity Using LC-MS/MS.

Three chromatographic methods were developed, optimized and validated for Paracetamol (PAR), Orphenadrine citrate (Or.cit) and Caffeine (CAF) determination in their mixture and in presence of PAR toxic impurity; P-aminophenol (PAP) in tablets. The first method is based on a thin layer chromatography combined with densitometry. Separation was achieved using silica gel 60 F254 TLC plates and dichloromethane:methanol:acetone:glacial acetic acid (9:1:0.5:0.3, v/v/v) as a developing system at 230 nm. The second method is based on high-performance liquid chromatography with diode array detection. The proposed compounds are separated on a reversed phase C18 analytical column using phosphate buffer (pH 9; 0.05 M) and methanol (80:20, v/v) at 1.2 mL/min. Linear regressions are obtained in the range of 1-500 µg/mL, 25-1000 µg/mL and 1-400 µg/mL for PAR, Or.cit and CAF, respectively. Quantification of the toxic PAP is carried out using LC-MS-MS by electrospray ionization in the positive mode using triple quadrupole mass spectrometry. The limit of quantification for PAP is 1 ng/mL. All methods are validated according to the ICH guidelines and successfully applied to determine PAR, Or.cit, CAF and PAP in pure powder and in combined tablets dosage form without interference from excipients.

Guest-Induced Ultrasensitive Detection of Multiple Toxic Organics and Fe3+ Ions in a Strategically Designed and Regenerative Smart Fluorescent Metal-Organic Framework.

Luminescent metal-organic frameworks (LMOFs) are promising functional materials for sustainable applications, where an analyte-induced multiresponsive system with good recyclability is beneficial for detecting numerous lethal pollutants. We designed and built the dual-functionalized, three-dimensional Zn(II)-framework [Zn3( bpg)1.5( azdc)3]·(DMF)5.9·(H2O)1.05 (CSMCRI-1) using an -OH group-integrated bpg linker and a -N═N- moiety containing H2 azdc ligand, which functions as a unique tetrasensoric fluorescent probe. The activated CSMCRI-1 (1') represents the hitherto unreported pillar-layer framework for extremely selective fluorescence quenching by nitrofurazone antibiotics as well as explosive nitro-aromatic 2,4,6-trinitrophenol, where ultrasensitive detection is achieved for both the electron-lacking analytes. Impressively, 1' represents the first ever MOF for significant fluorescence "turn-on" detection of toxic and electron-rich 4-aminophenol in the concurrent presence of isomeric analogues. Density functional theory calculations highlight the specific importance of pillar functionalization in the "turn-on" or "turn-off" responses of 1' by electronically divergent toxic organics and provide further proof of supramolecular interactions between the framework and analytes. The fluorescence intensity of 1' dramatically quenches by a trace amount of Fe3+ ions over other competing metal ions, alongside visible colorimetric change of the framework in solid and solution phase upon Fe3+ encapsulation. The sensing ability of 1' remains unaltered for multiple cycles toward all lethal pollutants. The sensing mechanism is attributed to both dynamic and static quenching as well as resonance energy transfer, which strongly comply with the predictions of theoretical simulations. Considering the long-term and real-time monitoring, AND as well as OR molecular logic gates are constructed based on the discriminative fluorescence response for each analyte that provides a platform to fabricate smart LMOFs with multimode logic operations.

Electrochemical sensor based on palladium-reduced graphene oxide modified with gold nanoparticles for simultaneous determination of acetaminophen and 4-aminophenol.

Herein, a newly developed electrochemical sensor base on the nanohybrid of palladium-reduced graphene oxide modified with gold nanoparticles (Au/Pd/rGO) was established, which was prepared by electrodeposing Au nanoparticles on Pd/rGO modified on a glass carbon electrode. The morphologies and microstructures of the as-prepared nanohybrid were characterized by X-ray photoelectron spectroscopy, Scanning electron microscopy and Infrared spectroscopy. And, experiment results showed that the prepared Au/Pd/rGO nanohybrid exhibited excellent electrocatalytic- activity toward the redox of acetaminophen (PA) and 4-aminophenol (4-AP) simultaneously. The linear detection ranges were 1.00-250.00µM for PA and 1.00-300.00µM for 4-AP, with the detection limits of 0.30µM for PA and 0.12µM for 4-AP, respectively. Because of the excellent performance of lower detection, wider linear range and better selectivity, the prepared Au/Pd/rGO nanohybrid with more potential applications was a promising candidate for advanced electrode material in electrochemical sensing field.

Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet.

Importance: Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective: To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Design and Setting: Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association-approved analytical procedures. Analytical findings were compared against the label information. Exposures: Products marketed and sold as selective androgen receptor modulators. Main Outcomes and Measures: Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Results: Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products (59%). Conclusions and Relevance: In this limited investigation involving chemical analyses of 44 products marketed as selective androgen receptor modulators and sold via the internet, most products contained unapproved drugs and substances. Only 52% contained selective androgen receptor modulators and many were inaccurately labeled.

Ultrasensitive and selective 4-aminophenol chemical sensor development based on nickel oxide nanoparticles decorated carbon nanotube nanocomposites for green environment.

Nickel oxide nanoparticles decorated carbon nanotube nanocomposites (NiO·CNT NCs) were prepared in a basic medium by using facile wet-chemical routes. The optical, morphological, and structural properties of NiO·CNT NCs were characterized using Fourier transformed infra-red (FT-IR), Ultra-violet visible (UV/Vis) spectroscopy, field-emission scanning electron microscopy (FESEM), X-ray energy dispersed spectroscopy (XEDS), X-ray photoelectron spectroscopy (XPS), and powder X-ray diffraction (XRD) methods. Selective 4-aminophenol (4-AP) chemical sensor was developed by a flat glassy carbon electrode (GCE, surface area: 0.0316cm2) fabricated with a thin-layer of NCs. Electrochemical responses including higher sensitivity, large dynamic range (LDR), limit of detection (LOD), and long-term stability towards 4-AP were obtained using the fabricated chemical sensors. The calibration curve was found linear (R2=0.914) over a wide range of 4-AP concentration (0.1nmol/L-0.1mol/L). In perspective of slope (2×10-5µA/µM), LOD and sensitivity were calculated as 15.0±0.1pM and ~6.33×10-4µA/(µM·cm) respectively. The synthesized NiO·CNT NCs using a wet-chemical method is a significant route for the development of ultrasensitive and selective phenolic sensor based on nano-materials for environmental toxic substances. It is suggested that a pioneer and selective development of 4-AP sensitive sensor using NiO·CNT NCs by a facile and reliable current vs voltage (I-V) method for the major application of toxic agents in biological, green environmental, and health-care fields in near future.

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds.

BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a Cl-/HCO3 - channel. F508del, the most common CF-associated mutation, causes both gating and biogenesis defects in the CFTR protein. This paper describes the optimization of two fluorescence assays, capable of measuring CFTR function and cellular localization, and their use in a pilot drug screen. EXPERIMENTAL APPROACH: HEK293 cells expressing YFP-F508del-CFTR, in which halide sensitive YFP is tagged to the N-terminal of CFTR, were used to screen a small library of compounds based on the VX-770 scaffold. Cells expressing F508del-CFTR-pHTomato, in which a pH sensor is tagged to the fourth extracellular loop of CFTR, were used to measure CFTR plasma membrane exposure following chronic treatment with the novel potentiators. KEY RESULTS: Active compounds with efficacy ~50% of VX-770, micromolar potency, and structurally distinct from VX-770 were identified in the screen. The F508del-CFTR-pHTomato assay suggests that the hit compound MS131A, unlike VX-770, does not decrease membrane exposure of F508del-CFTR. CONCLUSIONS AND IMPLICATIONS: Most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations.

Development of a Quasi-Steady Flow Electrochemical Paper-Based Analytical Device.

An electrochemical paper-based analytical device (ePAD) was developed for quasi-steady flow detection at microwire electrodes, for the first time. The device implements a fan shaped geometry connected to an analysis channel whereby solution is pulled from an inlet, through a channel, and into the steadily increasing capillary network of the fan. The network counteracts the decrease in solution flow rate associated with increasing viscosity within the channel, generating quasi-steady flow within the analysis channel. Microwire electrodes were embedded between two paper layers within the analysis channel, such that solution flow occurred on both sides of the wire electrodes. The quasi-steady flow ePAD increased the current by 2.5 times and 0.7 times from a saturated channel with no flow and from a single-layer paper device with flow, respectively. Amperometric detection was used for flow injection analysis (FIA) of multiple analytes at both Au and Pt microwire working electrodes, both of which provided similar sensitivity (ca. 0.2 mM-1) when normalized to the same standard. The two-layer paper devices provided a detection limit of 31 µM for p-aminophenol (PAP) using Pt electrodes and was also used to detect enzyme activity for the reaction of ß-galactosidase with p-aminophenyl-galactopyranoside (PAPG). Measured enzyme kinetics provided similar Vmax (0.079 mM/min) and Km (0.36 mM) values as those found in the literature. This device shows great promise toward use in enzyme-linked immunosorbent assays or other analytical techniques where flow or washing steps are necessary. The developed sensor provides a simple and inexpensive device capable of performing multiple injection analysis with steady-flow and online detection that would normally require an external pump to perform.