Diphenylamine NSAIDs are highly prescribed therapeutics for chronic pain despite causing symptomatic hepatotoxicity through mitochondrial damage in five percent of patients taking them. Differences in toxicity are attributed to structural modifications to the diphenylamine scaffold rather than its inherent toxicity. We hypothesize that marketed diphenylamine NSAID substituents affect preference and efficiency of bioactivation pathways and clearance. We parsed the FDA DILIrank hepatotoxicity database and modeled marketed drug bioactivation into quinone-species metabolites to identify a family of seven clinically relevant diphenylamine NSAIDs. These drugs fell into two subgroups, i.e., acetic acid and propionic acid diphenylamines, varying in hepatotoxicity risks and modeled bioactivation propensities. We carried out steady-state kinetic studies to assess bioactivation pathways by trapping quinone-species metabolites with dansyl glutathione. Analysis of the glutathione adducts by mass spectrometry characterized structures while dansyl fluorescence provided quantitative yields for their formation. Resulting kinetics identified four possible bioactivation pathways among the drugs, but reaction preference and efficiency depended upon structural modifications to the diphenylamine scaffold. Strikingly, diphenylamine dihalogenation promotes formation of quinone metabolites through four distinct metabolic pathways with high efficiency, whereas those without aromatic halogen atoms were metabolized less efficiently through two or fewer metabolic pathways. Overall metabolism of the drugs was comparable with bioactivation accounting for 4-13% of clearance. Lastly, we calculated daily bioload exposure of quinone-species metabolites based on bioactivation efficiency, bioavailability, and maximal daily dose. The results revealed stratification into the two subgroups; propionic acid diphenylamines had an average four-fold greater daily bioload compared to acetic acid diphenylamines. However, the lack of sufficient study on the hepatotoxicity for all drugs prevents further correlative analyses. These findings provide critical insights on the impact of diphenylamine bioactivation as a precursor to hepatotoxicity and thus, provide a foundation for better risk assessment in drug discovery and development.

Electro-responsive poly(diphenylamine)(PDPA)/Fe3O4 composite particles were prepared by the synthesis of PDPA particles using a chemical oxidative polymerization technique followed by loading nano-sized Fe3O4 particles onto PDPA via a chemical co-precipitation process. The morphological image of the PDPA/Fe3O4 particles was characterized by scanning electron microscope and transmission electron microscope. The crystalline structure was scrutinized by X-ray diffraction. The rheological characteristics of the suspension composed of PDPA/Fe3O4 particles suspended in silicone oil were investigated by a rotation rheometer, demonstrating standard electrorheological (ER) characteristics with a dramatic increase in shear stress and dynamic moduli under the application of an electrical field strength. The shear stress curves under an electrical field could be described using the Bingham model and the yield stress showed a power-law relationship with the electric field strength with an exponent of 1.5, following the conduction model. Furthermore, the frequency-dependent dielectric behaviors of the PDPA/Fe3O4 ER suspension was tested using an inductance (L)-capacitance (C)-resistance (R) (LCR) meter. The dielectric properties were well described using the Cole-Cole equation and were consistent with the results of the ER experiments.

Epithelial to mesenchymal transition (EMT) is a cellular program that converts non-motile epithelial cells into invasive mesenchymal cells. EMT is implicated in cancer metastasis, chemo-resistance, cancer progression, and generation of cancer stem cells (CSCs). Inducing mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is proposed as a novel strategy to target triple negative and tamoxifen-resistant breast cancer. Triple negative breast cancer (TNBC) is characterized by the loss of hormone receptors, a highly invasive mesenchymal phenotype, and a lack of targeted therapy. Estrogen receptor-positive breast cancer can be targeted by tamoxifen, an ER antagonist. However, these cells undergo EMT over the course of treatment and develop resistance. Thus, there is an urgent need to develop therapeutic interventions to target these aggressive cancers. In this study, we examined the role of novel diphenylamine analogs in converting the mesenchymal phenotype of MDA-MB-231 TNBC cells to a lesser aggressive epithelial phenotype. Using analog-based drug design, a series of diphenylamine analogs were synthesized and initially evaluated for their effect on E-cadherin protein expression and changes incell morphology, which was quantified by measuring the spindle index (SI) value. Selected compound 1 from this series increases the expression of E-cadherin, a primary marker for epithelial cells, and decreases the mesenchymal markers SOX2, ZEB1, Snail, and vimentin. The increase in epithelial markers and the decrease in mesenchymal markers are consistent with a phenotypic switch from spindle-like morphology to cobblestone-like morphology. Furthermore, Compound 1 decreases spheroid viability, cell migration, and cell proliferation in triple negative BT-549 and tamoxifen-resistant MCF-7 breast cancer cells.

Cyclooxygenase (COX) enzymes are molecular targets of nonsteroidal anti-inflammatory drugs (NSAIDs), the most used medication worldwide. However, the COX enzymes are not the sole molecular targets of NSAIDs. Recently, we showed that two NSAIDs, diclofenac and meclofenamate, also act as openers of Kv7.2/3 K(+) channels underlying the neuronal M-current. Here we designed new derivatives of diphenylamine carboxylate to dissociate the M-channel opener property from COX inhibition. The carboxylate moiety was derivatized into amides or esters and linked to various alkyl and ether chains. Powerful M-channel openers were generated, provided that the diphenylamine moiety and a terminal hydroxyl group are preserved. In transfected CHO cells, they activated recombinant Kv7.2/3 K(+) channels, causing a hyperpolarizing shift of current activation as measured by whole-cell patch-clamp recording. In sensory dorsal root ganglion and hippocampal neurons, the openers hyperpolarized the membrane potential and robustly depressed evoked spike discharges. They also decreased hippocampal glutamate and GABA release by reducing the frequency of spontaneous excitatory and inhibitory post-synaptic currents. In vivo, the openers exhibited anti-convulsant activity, as measured in mice by the maximal electroshock seizure model. Conversion of the carboxylate function into amide abolished COX inhibition but preserved M-channel modulation. Remarkably, the very same template let us generating potent M-channel blockers. Our results reveal a new and crucial determinant of NSAID-mediated COX inhibition. They also provide a structural framework for designing novel M-channel modulators, including openers and blockers.

Computational studies have suggested that the integration of secondary amine as donor groups in the structure of unsymmetrical zinc phthalocyanine (ZnPc) should have positive effects on photovoltaic performance, once the molecule is integrated as light harvester in dye sensitized solar cells (DSSCs). Aiming at obtaining experimental confirmation, we synthesized a peripherally substituted push-pull ZnPc bearing three electron donating diphenylamine substituents and a carboxylic acid anchoring group and integrated it as sensitizer in TiO2-based DSSCs. Detailed functional characterization of solar energy converting devices resulted in ruling out the original hypothesis. The causes of this discrepancy have been highlighted, leading to a better understanding of the conditions for an effective design of push-pull diarylamino substituted ZnPcs for DSSCs.

In this work, new information concerning the optical properties of black phosphorus (BP) sheets chemically/electrochemically functionalized with diphenyl amine (DPA) and its macromolecular compound (poly(diphenylamine) (PDPA)) in the absence/presence of phosphotungstic acid (PTA) is reported. Raman scattering and FTIR spectroscopy studies indicate that the interaction of BP with PTA leads to the elimination of the PxOy layer onto the surface of the BP sheets. In the case of the chemical interaction of BP with DPA, the reaction product corresponds to DPA chemically functionalized BP sheets having an imino-phosphorane (IP) structure. The electrochemical oxidation of BP sheets chemically functionalized with DPA in the presence of PTA leads to an increase in the weight of P-N bonds as a consequence of the generation of PDPA doped with the PTA heteropolyanions, as shown by FTIR spectroscopy and Raman scattering. This process is evidenced by a shift of the Raman line from 362 cm-1 to 378 cm-1, assigned to the A1g mode. This change was explained by taking into account the compression of the layers containing P atoms, which is induced by PDPA macromolecular chains. The decrease in the intensity of the PL spectra of DPA as well as PDPA, in the presence of BP, indicates that BP acts as a PL quenching agent for these compounds. A preferential orientation of the PDPA doped with the PTA heteropolyanions on the surface of BP sheets is highlighted by the variation of the binding angle of the PDPA on the surface of BP sheets from 44.7° to 39.9°.

Diphenylamine (DPA) is a common soil and water contaminant. A Pseudomonas putida strain, recently isolated from a wastewater disposal site, was efficient in degrading DPA. Thorough knowledge of the metabolic capacity, genetic stability and physiology of bacteria during biodegradation of pollutants is essential for their future industrial exploitation. We employed genomic, proteomic, transcription analyses and plasmid curing to (i) identify the genetic network of P. putida driving the microbial transformation of DPA and explore its evolution and origin and (ii) investigate the physiological response of bacterial cells during degradation of DPA. Genomic analysis identified (i) two operons encoding a biphenyl (bph) and an aniline (tdn) dioxygenase, both flanked by transposases and (ii) two operons and several scattered genes encoding the ortho-cleavage of catechol. Proteomics identified 11 putative catabolic proteins, all but BphA1 up-regulated in DPA- and aniline-growing cells, and showed that the bacterium mobilized cellular mechanisms to cope with oxidative stress, probably induced by DPA and its derivatives. Transcription analysis verified the role of the selected genes/operons in the metabolic pathway: DPA was initially transformed to aniline and catechol by a biphenyl dioxygenase (DPA-dioxygenase); aniline was then transformed to catechol which was further metabolized via the ortho-cleavage pathway. Plasmid curing of P. putida resulted in loss of the DPA and aniline dioxygenase genes and the corresponding degradation capacities. Overall our findings provide novel insights into the evolution of the DPA degradation pathway and suggests that the degradation capacity of P. putida was acquired through recruitment of the bph and tdn operons via horizontal gene transfer.

The realization of operationally stable blue organic light-emitting diodes is a challenging issue across the field. While device optimization has been a focus to effectively prolong device lifetime, strategies based on molecular engineering of chemical structures, particularly at the subatomic level, remains little. Herein, we explore the effect of targeted deuteration on donor and/or acceptor units of thermally activated delayed fluorescence emitters and investigate the structure-property relationship between intrinsic molecular stability, based on isotopic effect, and device operational stability. We show that the deuteration of the acceptor unit is critical to enhance the photostability of thermally activated delayed fluorescence compounds and hence device lifetime in addition to that of the donor units, which is commonly neglected due to the limited availability and synthetic complexity of deuterated acceptors. Based on these isotopic analogues, we observe a gradual increase in the device operational stability and achieve the long-lifetime time to 90% of the initial luminance of 23.4 h at the luminance of 1000 cd m-2 for thermally activated delayed fluorescence-sensitized organic light-emitting diodes. We anticipate our strategic deuteration approach provides insights and demonstrates the importance on structural modification materials at a subatomic level towards prolonging the device operational stability.

Forensic analysis of smokeless powder particles recovered from the debris of an improvised explosive device can provide information about the type of smokeless powder used and can aid investigation efforts. In this study, quantitative methods were used to yield information about the difference in the chemical composition of the particles pre- and post-blast. The technique, gas chromatography/vacuum ultraviolet spectroscopy (GC/VUV), was able to quantify nitroglycerin, 2,4-dinitrotoluene, diphenylamine, ethyl centralite, and di-n-butyl phthalate in pre- and post-blast smokeless powder particles using heptadecane as an internal standard. Post-blast debris was obtained via controlled explosions with assistance from the Indiana State Police Bomb Squad. Two galvanized steel and two polyvinyl chloride pipe bombs were assembled. Two devices contained single-base smokeless powder and two contained double-base smokeless powder. 2,4-dinitrotoluene and diphenylamine were successfully quantified in the single-base smokeless powder post-blast debris while nitroglycerin, diphenylamine, and ethyl centralite were successfully quantified in the double-base smokeless powder post-blast debris. Compounds were detected at concentrations as low as 9 μg of 2,4-dinitrotoluene per mg, <3 μg of diphenylamine per mg, 131 μg of nitroglycerin per mg, and <3 μg of ethyl centralite per mg. Concentration changes between pre- and post-blast smokeless powder particles were determined as well as microscopic differences between pre- and post-blast debris for both smokeless powders in all devices. To our knowledge, this is the first use of GC/VUV for the quantification of explosives.

Using patch-clamp and molecular biological techniques, we identified and characterized membrane currents most likely generated by an electrogenic Na+-HCO3- cotransporter (NBCe) in acutely dissociated bovine parotid acinar (BPA) cells. When BPA cells were dialysed with a N-methyl-D-glucamine (NMDG)-glutamate-rich pipette solution, switching a Na-glutamate-rich, nominally HCO3--free bath solution to the one containing 25 mM HCO3-, but not Cl-, elicited a whole-cell current with a linear current-voltage relation. The HCO3- evoked current was abolished by total replacement of extracellular Na+ (Na+o) with NMDG or by 0.5 mM 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), and was only partially supported by Li+o, but not by K+o, Cs+o, and cholineo. The reversal potential shift of DIDS (0.5 mM)-sensitive current induced by a change of [Na+]o corresponded to an apparent coupling ratio of HCO3- to Na+ of 2. RT-PCR analysis showed the presence of transcripts of NBCe1-B, but not NBCe1-A in BPA cells. Electrophysiological and pharmacological properties of whole-cell currents recorded from HEK293 cells transfected with the NBCe1-B, which was cloned from BPA cells resembled those of the native currents. Non-invasive measurements of membrane potential changes in the cell-attached patch configuration indicated that an NBCe activity is present in intact unstimulated BPA cells bathed in a 25 mM HCO3--containing solution. Collectively, these results not only suggest that an NBCe is present, functional and may be mediated, at least in part, by NBCe1-B in BPA cells, but also provide the first electrophysiological characterization of transport properties of NBCe expressed in native exocrine glands.

Inverted colloidal-nanocrystal-based LEDs (NC-LEDs) are highly interesting and invaluable for large-scale display technology and flexible electronics. Semiconductor nanorods (NRs), in addition to the tunable wavelengths of the emitted light (achieved, for example, by the variation of the NR diameter or the diameter of core in a core-shell configuration), also exhibit linearly polarized emission, a larger Stokes shift, faster radiative decay, and slower bleaching kinetics than quantum dots (QDs). Despite these advantages, it is difficult to achieve void-free active NR layers using simple spin-coating techniques. Herein, we employ electrophoretic deposition (EPD) to make closely packed, vertically aligned CdSe/CdS core/shell nanorods (NRs) as the emissive layer. Following an inverted architecture, the device fabricated yields an external quantum efficiency (EQE) of 6.3% and a maximum luminance of 4320 cd/m2 at 11 V. This good performance can be attributed to the vertically aligned NR layer, enhancing the charge transport by reducing the resistance of carrier passage, which is supported by our finite element simulations. To the best of our knowledge, this is the first time vertically aligned NR layers made by EPD have been reported for the fabrication of NC-LEDs and the device performance is one of the best for inverted red NR-LEDs. The findings presented in this work bring forth a simple and effective technique for making vertically aligned NRs, and the mechanism behind the NR-LED device with enhanced performance using these NRs is illustrated. This technique may prove useful to the development of a vast class of nanocrystal-based optoelectronics, including solar cells and laser devices.

Adsorption processes of 1,4-phenylene diisothiocyanate (PDITC) on two new platforms of the type graphene oxide (GO) sheets and GO layers functionalization with polydiphenylamine (PDPA) are studied by Raman scattering and photoluminescence (PL). An interaction in solid state phase of the two constituents, i.e. PDITC and GO sheets, and a deposition of PDITC onto the PDPA functionalized GO layers, respectively, by the drop casting method, were performed. In the first case, it is shown that interaction in solid state phase of GO with PDITC leads to an intercalation of the organic compound between GO sheets simultaneously with the appearance of the o-thiocarbamate groups, that induces: (i) an enhancement of the PDITC Raman lines situated in the 400-800 and 1000-1300 cm-1 spectral ranges, (ii) a change in the ratio between the relative intensities of the two Raman lines peaked at 1585 and 1602 cm-1 accompanied by an up-shift in the case of the second line and (iii) a down-shift of the PDTIC PL band from 502 to 491 nm. Using cyclic voltammetry, an electrochemical functionalization of the GO layers with PDPA doped with H3PMo12O40 heteropolyanions takes place, as demonstrated by Raman scattering and FTIR spectroscopy. The presence of the amine groups in the molecular structure of the doped PDPA functionalized GO layers induces a chemical adsorption of PDITC on this platform, when the thiourea groups appear simultaneously with o-thiocarbamate groups. A chemical mechanism is proposed to take place at the interface of the GO sheets and the doped PDPA functionalized GO layers, respectively, with PDITC.

D-penicillamine (PA) is a sulfur group-containing drug prescribed for various health issues, but overdoses have adverse effects. Therefore, regular, selective, and sensitive sensing is essential to reduce the need for further treatment. In this study, diphenylamine (DPA) was electropolymerized in an aqueous acidic medium. The PA detection sensitivity, selectivity, and limit of detection were enhanced by electropolymerizing DPA on an electrochemically reduced graphene oxide (ERGO)/glassy carbon (GC) surface. The formation of p-DPA and ERGO was investigated using various techniques. The as-prepared p-DPA@ERGO/GC revealed the excellent redox-active (N-C to N=C) sites of p-DPA. The p-DPA@ERGO/GC electrode exhibited excellent electrochemical sensing ability towards PA determination because of the presence of the -NH-functional moiety and effective interactions with the -SH group of PA. The p-DPA@ERGO/GC exhibited a high surface coverage of 9.23 × 10-12 mol cm-2. The polymer-modified p-DPA@ERGO/GC electrode revealed the amperometric determination of PA concentration from the 1.4 to 541 μM wide range and the detection limit of 0.10 μM. The real-time feasibility of the developed p-DPA@ERGO/GC electrode was tested with a realistic PA finding in human blood serum samples and yielded a good recovery of 97.5-101.0%, confirming the potential suitability in bio-clinical applications.

The enantioselective tandem Friedel-Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by a diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee).

Pullulan and glycogen have many applications and physiological functions. However, to date, it has been unknown where and how the pullulan is synthesized in the yeast cells and if cell wall structure of the producer can affect pullulan and glycogen biosynthesis.

The aerobic and thermal stability of quantum-dot light-emitting diodes (QLEDs) is an important factor for the practical applications of these devices under harsh environmental conditions. We demonstrate all-solution-processed amber QLEDs with an external quantum efficiency (EQE) of > 14% with almost negligible efficiency roll-off (droop) and a peak brightness of > 600,000 cd/m2, unprecedented for QLEDs fabricated under ambient air conditions. We investigate the device efficiency and brightness level at a temperature range between - 10 and 85 °C in a 5-step cooling/heating cycle. We conducted the experiments at brightness levels higher than 10,000 cd/m2, required for outdoor lighting applications. Our device performance proves thermal stability, with minimal standard deviation in the performance parameters. Interestingly, the device efficiency parameters recover to the initial values upon returning to room temperature. The variations in the performance are correlated with the modification of charge transport characteristics and induced radiative/non-radiative exciton relaxation dynamics at different temperatures. Being complementary to previous studies on the subject, the present work is expected to shed light on the potential feasibility of realizing aerobic-stable ultrabright droop-free QLEDs and encourage further research for solid-state lighting applications.

The electrochemical behavior of new electrode materials based on poly-N-phenylanthranilic acid (P-N-PAA) composites with reduced graphene oxide (RGO) was studied for the first time. Two methods of obtaining RGO/P-N-PAA composites were suggested. Hybrid materials were synthesized via in situ oxidative polymerization of N-phenylanthranilic acid (N-PAA) in the presence of graphene oxide (GO) (RGO/P-N-PAA-1), as well as from a P-N-PAA solution in DMF containing GO (RGO/P-N-PAA-2). GO post-reduction in the RGO/P-N-PAA composites was carried out under IR heating. Hybrid electrodes are electroactive layers of RGO/P-N-PAA composites stable suspensions in formic acid (FA) deposited on the glassy carbon (GC) and anodized graphite foil (AGF) surfaces. The roughened surface of the AGF flexible strips provides good adhesion of the electroactive coatings. Specific electrochemical capacitances of AGF-based electrodes depend on the method for the production of electroactive coatings and reach 268, 184, 111 F∙g-1 (RGO/P-N-PAA-1) and 407, 321, 255 F∙g-1 (RGO/P-N-PAA-2.1) at 0.5, 1.5, 3.0 mA·cm-2 in an aprotic electrolyte. Specific weight capacitance values of IR-heated composite coatings decrease as compared to capacitance values of primer coatings and amount to 216, 145, 78 F∙g-1 (RGO/P-N-PAA-1IR) and 377, 291, 200 F∙g-1 (RGO/P-N-PAA-2.1IR). With a decrease in the weight of the applied coating, the specific electrochemical capacitance of the electrodes increases to 752, 524, 329 F∙g-1 (AGF/RGO/P-N-PAA-2.1) and 691, 455, 255 F∙g-1 (AGF/RGO/P-N-PAA-1IR).

This work presents an efficient method for treating industrial wastewater containing aniline and benzothiazole, which are refractory to conventional treatments. A combination of heterogeneous photocatalysis operating in a fluidised bed reactor is studied in order to increase mass transfer and reduce reaction times. This process uses a manganese dioxide catalyst supported on granular activated carbon with environmentally friendly characteristics. The manganese dioxide composite is prepared by hydrothermal synthesis on carbon Hydrodarco® 3000 with different active phase ratios. The support, the metal oxide, and the composite are characterised by performing Brunauer, Emmett, and Teller analysis, transmission electron microscopy, X-ray diffraction analysis, X-ray fluorescence analysis, UV-Vis spectroscopy by diffuse reflectance, and Fourier transform infrared spectroscopy in order to evaluate the influence of the metal oxide on the activated carbon. A composite of MnO2/GAC (3.78% in phase α-MnO2) is obtained, with a 9.4% increase in the specific surface of the initial GAC and a 12.79 nm crystal size. The effect of pH and catalyst load is studied. At a pH of 9.0 and a dose of 0.9 g L-1, a high degradation of aniline and benzothiazole is obtained, with an 81.63% TOC mineralisation in 64.8 min.

The study of palladium-catalyzed amination of bromobenzene with aromatic and heterocyclic amines, widely used in the synthesis of organic semiconductors, was performed. The best conditions for the coupling of aryl bromides with carbazole, diphenylamine, phenoxazine, phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, and their derivatives have been developed. Based on the results, nine new star-shaped organic semiconductors, exhibiting up to 100% fluorescent quantum yield in the 400-550 nm range, have been synthesized in good yields. The TDDFT calculations of the absorption spectra revealed a good correlation with experimental results and slight solvatochromic effects with a change in the polarity of the solvent.

Honey adulteration, where a range of sugar syrups is used to increase bulk volume, is a common problem that has significant negative impacts on the honey industry, both economically and from a consumer confidence perspective. This paper investigates High-Performance Thin Layer Chromatography (HPTLC) for the authentication and detection of sugar adulterants in honey. The sugar composition of various Australian honeys (Manuka, Jarrah, Marri, Karri, Peppermint and White Gum) was first determined to illustrate the variance depending on the floral origin. Two of the honeys (Manuka and Jarrah) were then artificially adulterated with six different sugar syrups (rice, corn, golden, treacle, glucose and maple syrup). The findings demonstrate that HPTLC sugar profiles, in combination with organic extract profiles, can easily detect the sugar adulterants. As major sugars found in honey, the quantification of fructose and glucose, and their concentration ratio can be used to authenticate the honeys. Quantifications of sucrose and maltose can be used to identify the type of syrup adulterant, in particular when used in combination with HPTLC fingerprinting of the organic honey extracts.