Phosphonium-mediated cyclization of N-(2-aminophenyl)thioureas: efficient synthesis of 2-aminobenzimidazoles

BOP efficiently promoted the phosphonium-mediated cyclization of thioureas, leading to a convenient synthesis of 2-aminobenzimidazoles. Compared to conventional methods, the reactions were complete at room temperature with times ranging from a few minutes to 1 h in near quantitative yields. This method is also applicable to the synthesis of more challenging structures such as 2-akylaminobenzimidazoles and 2-(N-acyl)-aminobenzimidazoles. The methodology described herein represents a mild and efficient route to a variety of 2-aminobenzimidazoles.     

1-C-Alkyl imino-d-xylitol and -l-arabinitol derivatives obtained via nucleophilic addition to pentose-derived N-tert-butanesulfinyl imines: sugar- versus chiral auxiliary-induced stereoselectivity

The stereoselective synthesis of 1-C-alkyl iminosugars in the d-xylo and l-arabino series as potential drugs for the treatment of lysosomal diseases has been achieved. The key step involves nucleophilic addition to pentodialdofuranose-derived imines generated using enantiopure tert-butanesulfinamide. Depending on the pentofuranose configuration and structure, the stereoselectivity of this reaction was found to be controlled either by the sugar moiety or by the stereogenic sulfur center.     

Surface crystallization of rapamycin on stents using a temperature induced process

Metallic drug eluting stents (DES) are usually prepared by coating with a drug-polymer matrix as a rate controlling diffusion barrier. However, coating materials may display numerous problems, thus carrier-free DES are desired, yet releasing drug over long period of time. For this, we are reporting a novel temperature induced (TI) crystallization process for coating rapamycin on stents. Rapamycin crystals with a defined morphology and target drug load were applied from supersaturated solution. This method enables fabrication of controllable and homogeneous crystalline coatings on stent scaffolds and allowing the drug to release for several weeks.     

Monte Carlo modelling for the in vivo lung monitoring of enriched uranium: Results of an international comparison

In order to assess the reliability of Monte Carlo (MC)-based numerical calibration of in vivo counting systems the EURADOS network supported a comparison of MC simulation of well-defined experiments. This action also provided training for the use of voxel phantoms. In vivo measurements of enriched uranium in a thoracic phantom have been carried out and the needed information to simulate these measurements was distributed to 17 participants. About half of the participants managed to simulate the measured counting efficiency without support from the organisers. Following additional support all participants managed to simulate the counting efficiencies within a typical agreement of ±5% with experiment.     

pH-Metric study of gamma-irradiated table sugar for dosimetry purpose

Table sugar has been studied for a long time as a dosimeter in radiation accident and in high-dose dosimetry by using different analytical techniques especially electron paramagnetic resonance (EPR) and optical absorption spectrometry (OA). In this work, we report the results obtained by pH-metry on gamma-irradiated sugar. Table sugar samples were exposed to gamma radiation with doses of 0.1–58 kGy. Aqueous solutions of sugar were prepared with different concentrations ranged from 1% to 60% (w/w). It was found that sugar solutions showed strong decrease of pH up to concentration of 10% (w/w) followed by a slow decrease for the concentrations between 10 and 60% (w/w). Two possible mechanisms are proposed to explain the acidity increasing of the sugar solutions based on the existence of a carbonyl radical induced by gamma irradiation in solid table sugar with an open ring structure. Results for radiation response, post-irradiation change, reading temperature, dose-rate effect and repeatability are presented in this study. The results showed that pH-metric/sugar solution is an adequate high-dose dosimetric system in the dose range of 0.1–10 kGy.     

Mesoporous γ‐Iron Oxide Nanoparticles for Magnetically Triggered Release of Doxorubicin and Hyperthermia Treatment

Mesoporous iron‐oxide nanoparticles (mNPs) were prepared by using a modified nanocasting approach with mesoporous carbon as a hard template. mNPs were first loaded with doxorubicin (Dox), an anticancer drug, and then coated with the thermosensitive polymer Pluronic F108 to prevent the leakage of Dox molecules from the pores that would otherwise occur under physiological conditions. The Dox‐loaded, Pluronic F108‐coated system (Dox@F108‐mNPs) was stable at room temperature and physiological pH and released its Dox cargo slowly under acidic conditions or in a sudden burst with magnetic heating. No significant toxicity was observed in vitro when Dox@F108‐mNPs were incubated with noncancerous cells, a result consistent with the minimal internalization of the particles that occurs with normal cells. On the other hand, the drug‐loaded particles significantly reduced the viability of cervical cancer cells (HeLa, IC₅₀=0.70 μm ), wild‐type ovarian cancer cells (A2780, IC₅₀=0.50 μm ) and Dox‐resistant ovarian cancer cells (A2780/AD, IC₅₀=0.53 μm ). In addition, the treatment of HeLa cells with both Dox@F108‐mNPs and subsequent alternating magnetic‐field‐induced hyperthermia was significantly more effective at reducing cell viability than either Dox or Dox@F108‐mNP treatment alone. Thus, Dox@F108‐mNPs constitute a novel soft/hard hybrid nanocarrier system that is highly stable under physiological conditions, temperature‐responsive, and has chemo‐ and thermotherapeutic modes of action.     

In vivo oral insulin delivery via covalent organic frameworks

With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy.

We report the successful use of a gastro-resistant covalent organic framework for in vivo oral delivery of insulin.     

Squarate complexes of some lanthanide ions in aqueous solution

The squarate complexes of Eu³⁺, Tb³⁺ and Tm³⁺ in aqueous solutions of 0.05M, 0.075M and 0.1M ionic strength are studied using the solvent extraction method. Effects of changes in the ionic strength on the stability constants of the complexes formed are discussed.     

Optimization of the preparation conditions of radioiodoepidepride: A dopamine D<Subscript>2</Subscript>receptor antagonist radioligand

Summary [¹²⁵I]iodepidepride, (s)-(-)-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[¹²⁵I]-iodo-2,3-dimethoxybenzamide is the iodine substituted analogue of isoremoxipride, both of which are very potent dopamine D₂-antagonists. Epidepride was radioiodinated using different oxidizing agents such as chloramine-T, iodogen, iodogen glass frit and hydrogen peroxide. Chloramine-T is a powerful oxidizing agent compared to both iodogen and hydrogen peroxide so that the side products, especially the chlorinated epidepride, decreases the radiochemical yield. This chlorinated epidepride is minimized in the case of iodogen and iodogen glass frit and are not observed in case of the non-chlorinated oxidizing agent hydrogen peroxide. TLC and HPLC were used to analyze the reaction components and to estimate both the radiochemical yield and purity. The reaction parameters such as reaction time, pH, epidepride and oxidizing agent concentrations and the stabilty of the final product were studied to optimize the radiochemical yield and purity. The optimized radiochemical yield was about 90% and the radiochemical purity of the final product was 99.9%.     

Fluorescence properties of recombinant tropomyosin containing tryptophan, 5-hydroxytryptophan and 7-azatryptophan

Tropomyosin mutants containing either tryptophan (122W), 5-hydroxytryptophan (5OH122W) or 7-azatryptophan (7N122W) have been expressed in Escherichia coli and their fluorescence properties studied. The fluorescent amino acids were located at position 122 of the tropomyosin primary sequence, corresponding to a solvent-exposed position c of the coiled-coil heptapeptide repeat. The emission spectrum of the probe in each mutant is blue-shifted slightly with respect to that of the probe in water. The fluorescence anisotropy decays are single exponential, with a time constant of 2-3 ns while the fluorescence lifetimes of the probes incorporated into the proteins, in water, are nonexponential. Because tryptophan in water has an intrinsic nonexponential fluorescence decay, it is not surprising that the fluorescence decay of 122W is well described by a triple exponential. The fluorescence decays in water of the nonnatural amino acids 5-hydroxytryptophan and 7-azatryptophan (when emission is collected from the entire band) are single exponential. Incorporation into tropomyosin induces triple-exponential fluorescence decay in 5-hydroxytryptophan and double-exponential fluorescence decay in 7-azatryptophan. The range of lifetimes observed for 5-hydroxyindole and 5-hydroxytryptophan at high pH and in the nonaqueous solvents were used as a base with which to interpret the lifetimes observed for the 5OH122W and indicate that the chromophore exists in several solvent environments in both its protonated and unprotonated forms in 5OH122W.