A Ligand-Directed Nitrophenol Carbonate for Transient in situ Bioconjugation and Drug Delivery

Here we report the first use of ligand-directed proximity accelerated bioconjugation chemistry in the tandem delivery and release of a therapeutic payload. To do this, we designed a nitrophenol carbonate for ligand-directed in situ bioconjugation of a prodrug payload to a protein. The transient nature of our conjugation chemistry renders the protein a depot for time-dependent release of active drug following hydrolysis and self-immolation. In our model system, using an immunostimulant prodrug, biotin ligand, and avidin protein, we observe release of bioavailable immunostimulant both spectroscopically and with an immune cell line over 48 h. Avidin co-crystalized with the nitrophenolate directing group verified the binding pose of the ligand and offered insight into the mechanism of in situ bioconjugation. Overall, this scaffold warrants further investigation for the time-dependent delivery of therapeutics and use in protein ligand pairs beyond biotin and avidin used for this work.     

Enhanced optical properties of ZnS–rGO nanocomposites for ultraviolet detection applications

In this research, fabrication and characterization of ultraviolet (UV) detectors based on zinc sulfide–reduced graphene oxide (rGO) nanocomposite with the focus on the wurtzite structure of zinc sulfide was carried out. The nanoparticles of ZnS were synthesized using chemical deposition method and annealed at 500?°C under flow of argon. X-ray diffraction pattern showed that ZnS with the wurtzite phase was formed at 500?°C. Here, rGO as a unique material with similar properties to graphene such as high electron transport was used in order to improve the optical properties of ZnS. For this purpose, rGO was added to ZnS with three different weight percentages of 5, 10 and 15. Scanning electron microscopy showed that ZnS nanoparticles were well placed in rGO sheets. The UV–visible spectra of the synthesized composites showed that with increasing rGO in composite, light absorption is increased. Photoluminescence (PL) spectra also showed that with increasing the percentage of rGO the generation of electron-hole in composite was increased and PL peak was enhanced. The effect of elevated generation of electron-hole pairs was apparent in optoelectrical properties of fabricated UV detectors based on the sample with higher concentration of rGO in composite. For this sample, the response time was decreased to 310 ms, and the sensitivity to UV irradiation was increased by 7.7 times.     

Anchoring of Copper(II) Schiff Base Complex into Aminopropyl-Functionalised MCM-41: A Novel,Efficient and Reusable Catalyst for Selective Oxidation of Alcohols

A copper(II) complex containing tetradentate N₂O₂ Schiff base ligand immobilized into aminopropyl-functionalised MCM-41 (mobile crystalline material number 41), was prepared and characterized by Fourier-transform infrared, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, N₂ adsorption–desorption and inductively coupled plasma analysis techniques. The novel heterogeneous catalyst, MCM-41-pr-NH₂-CuL, can be successfully applied for efficient and selective oxidation of different primary and secondary alcohols to the corresponding carbonyl compounds using hydrogen peroxide as an oxidant in acetonitrile at 60 °C. The effect of reaction parameters such as solvent, amount of catalyst, temperature and kind of oxidant on the oxidation of benzyl alcohol was also studied. The prepared catalyst could be recovered and reused four times without important loss of its catalytic performance. The heterogeneous MCM-41-pr-NH₂-CuL catalyst was found to be catalytically more active in the oxidation of alcohols compared to the similar type of copper(II) Schiff base complex in homogeneous media under the same reaction conditions.     

A walk around the decarboxylative C-S cross-coupling reactions

This review highlights a number of recent discoveries and advances in the construction of carbon-sulfur bonds through decarboxylative cross-coupling reactions between carboxylic acids and sulfur-containing coupling partners. Particular emphasis is placed on the mechanistic aspects of the reactions.     

Synthesis of nanosized SiC by low-temperature magnesiothermal reduction of nanocomposites of functionalized carbon nanotubes with MCM-48

Silicon carbide synthesis by a magnesiothermal method was investigated using MCM-48 as the silica source mechanically mixed with carbon nanotubes (CNTs) as the carbon source, and nanocomposites of MCM-48/functionalized CNTs (CNTF). SiC syntheses were carried out with different molar ratios of MCM-48, carbon and magnesium at 700?°C in argon. The MCM-48 and carbon nanotube starting materials and the SiC products were characterized by BET, XRD, FESEM, EDX and TEM. The effect of the carbon content and the type of CNTs (either functionalized or unfunctionalized) on the SiC synthesis was studied. The results show that an improved yield of SiC is obtained when the carbon nanotubes are functionalized, producing a better contact with the MCM-48. This improved contact between the reactants ensures a good degree of reaction in a stoichiometric mixture of silicon and carbon, with no improvement in product formation being achieved by the use of additional carbon. These findings suggest that the degree of contact between reactants is an important factor in the magnesiothermal synthesis of SiC. The SiC products from magnesiothermal synthesis of the functionalized nanocomposite precursors were shown by TEM and FESEM to have unusual nanofiber morphologies mimicking the morphology of the CNTF nanotubes.     

Profiling of rat urinary proteomic patterns associated with drug-induced nephrotoxicity using CE coupled with MS as a potential model for detection of drug-induced adverse effects

We have investigated urine obtained from Sprague Dawley rats before and after administration of cis-Platin, aiming at the definition of biomarkers for drug-induced cytotoxicity. Rats were treated with 3 or 6 mg/kg cis-Platin (i.p., single injection) and urine samples were collected before and after drug or saline treatment. Analysis of the low molecular weight proteome (<20 kDa) using capillary-electrophoresis coupled mass spectrometry allowed us to tentatively identify 34 urinary peptides that show significant differences between control and treated animals, and hence may serve as a potential biomarker for cis-Platin-induced nephrotoxicity. These biomarkers were confirmed in a blinded assessment of additional samples. The blinded data also revealed time-dependency of induced changes. Some of the potential biomarkers could be sequenced. This information revealed great similarity between cis-Platin-induced changes and significant changes in the urinary proteome of patients suffering from tubular injury (Fanconi syndrome). Our study strongly suggests that (drug-induced) nephrotoxicity can be detected with high accuracy in laboratory rodents using urinary proteome analysis. The effects observed are very similar to those seen in corresponding human diseases and similar approaches may be very helpful in evaluating drug-induced organ damage in preclinical animal models. This study aiming at the definition of biomarkers for drug-induced cytotoxicity may serve as a proof-of-principle for the use of urinary proteomics in assessment of drug-induced nephrotoxicity.     

Discharge characteristics of a modified oblique side weir in subcritical flow

Side weirs are frequently used in many water projects. Due to their position with respect to the flow direction, side weirs are categorized as plain, oblique and labyrinth. One of the advantages of an oblique side weir is the increase in the effective length of the weir for overflowing and, therefore, diverting more discharge with the same channel opening, weir height and flow properties (i.e., upstream discharge, upstream Froude number and so on). In this paper, an experimental set-up of a new design of an oblique side weir with asymmetric geometry has been studied. The hydraulic behavior of this kind of oblique side weir, with a constant opening length, different weir heights and asymmetric oblique angle, has been investigated in a subcritical situation. The results from over 200 test measurements show that this kind of weir is up to 2.33 times more efficient with respect to the conventional side weir in a rectangular channel among the tested conditions. Finally, the discharge coefficient as a function of geometrical and flow variables are presented for design engineers. In addition, a more precise relation has been obtained for flow with Froude numbers less than 0.4.     

Congener-specific tissue distribution of aroclor 1254 and a highly chlorinated environmental PCB mixture in rats

Polychlorinated biphenyl (PCB) mixtures were synthesized and marketed in Eastern European countries, but little is known abouttheir composition, distribution, ortoxicity. PCB-contaminated soil from the former production site of the Polish PCB mixture Chlorofen was collected, and the PCBs were extracted. An in vivo study was performed to investigate the PCB tissue distribution and biochemical effects of this soil extract in immature male Sprague-Dawley rats. Rats were administered 0.05 mmol/kg soil-extracted PCBs or Aroclor 1254 and sacrificed 7 days later, and congener-specific PCB profiles in selected tissues were determined. Distribution of SigmaPCBs (sum of 120 congeners) in tissues was primarily a function of lipid content of the tissues, except for the spleen, which retained more PCB than other tissues. Multivariate analysis of the PCB congener data showed that (a) congener profiles in tissues had changed, as compared to the parent mixture; (b) disposition and redistribution of individual congeners in vivo differed between both mixtures; and (c) more highly chlorinated congeners were retained in the spleens of both treatment groups. Differences in the induction of cytochrome P-450 1A and 2B subfamilies reflected the homologue composition of the respective mixtures and predict a different toxicity profile for Chlorofen than for Aroclor 1254.     

Characterization of Interactions between CTX-M-15 and Clavulanic Acid,Desfuroylceftiofur, Ceftiofur,Ampicillin, and Nitrocefin

Cefotaximase-Munich (CTX-M) extended-spectrum beta-lactamases (ESBLs) are commonly associated with Gram-negative, hospital-acquired infections worldwide. Several beta-lactamase inhibitors, such as clavulanate, are used to inhibit the activity of these enzymes. To understand the mechanism of CTX-M-15 activity, we have determined the crystal structures of CTX-M-15 in complex with two specific classes of beta-lactam compounds, desfuroylceftiofur (DFC) and ampicillin, and an inhibitor, clavulanic acid. The crystal structures revealed that Ser70 and five other residues (Lys73, Tyr105, Glu166, Ser130, and Ser237) participate in catalysis and binding of those compounds. Based on analysis of steady-state kinetics, thermodynamic data, and molecular docking to both wild-type and S70A mutant structures, we determined that CTX-M-15 has a similar affinity for all beta-lactam compounds (ceftiofur, nitrocefin, DFC, and ampicillin), but with lower affinity for clavulanic acid. A catalytic mechanism for tested β-lactams and two-step inhibition mechanism of clavulanic acid were proposed. CTX-M-15 showed a higher activity toward DFC and nitrocefin, but significantly lower activity toward ampicillin and ceftiofur. The interaction between CTX-M-15 and both ampicillin and ceftiofur displayed a higher entropic but lower enthalpic effect, compared with DFC and nitrocefin. DFC, a metabolite of ceftiofur, displayed lower entropy and higher enthalpy than ceftiofur. This finding suggests that compounds containing amine moiety (e.g., ampicillin) and the furfural moiety (e.g., ceftiofur) could hinder the hydrolytic activity of CTX-M-15.