Efficient oxidizing agents for determination of 2,10-disubstituted phenothiazines.

2,10-Disubstituted phenothiazines are the best drugs in psychiatry. Several methods for their analysis have been reported in the literature. The official methods are based on non-aqueous titration or spectrophotometry. Various oxidizing agents have been used for the spectrophotometric determination of 2,10-disubstituted phenothiazines, e.g. Ce(SO4)2, NH4VO3, K2S208, KIO4, KIO3, KBrO3, FeCl3, NaNO2, H2O2, chloramine T, p-benzoquinone, N-bromosuccinimide. Oxidation reactions of phenothiazines were also used for their determination by flow-injection methods.     

Chemistry-Crystallization-Microstructure Relations of Sol-Gel Derived Lanthanum Modified Lead Titanate Thin Films

Lanthanum modified lead titanate thin films have been obtained by the deposition of sol-gel solutions onto platinized (100) silicon substrates. Crystallization of perovskite films was achieved by thermal treatments at 650°C with slow or rapid heatings. Lead oxide excesses were used in the precursor solutions to counterbalance the lead losses produced during the thermal treatment. Rapid heatings and large excesses of lead produce a preferred orientation of the films. These films have more homogeneous and denser microstructures than slow heated films without lead excess.     

Flow-injection spectrophotometric determination of azithromycin in pharmaceutical formulations using p-chloranil in the presence of hydrogen peroxide.

A flow-injection (FI) spectrophotometric procedure exploiting merging zones is proposed for the determination of azithromycin in pharmaceutical formulations. The method is based on the reaction of azithromycin with tetrachloro-p-benzoquinone (p-chloranil) accelerated by hydrogen peroxide and conducted in a methanol medium, producing a purple-red color compound (lambda(max) = 540 nm). The FI system and the experimental conditions were optimized using a multivariate method. Beer's law is obeyed in a concentration range of 50 - 1600 microg mL(-1) with an excellent correlation coefficient (r = 0.9998). The detection limit and the quantification limit were 6.6 and 22.1 microg mL(-1), respectively. No interference was observed from the common excipients, and the recoveries were within 98.6 to 100.4%. The procedure was applied to the determination of azithromycin in pharmaceuticals with a high sampling rate (65 samples h(-1)). The results obtained by the proposed method were in good agreement with those obtained by the comparative method at 95% confidence level.     

Flow-injection spectrophotometric determination of novalgin in pharmaceuticals using micellar medium.

A sensitive flow-injection (FI) procedure with spectrophotometric detection in a micellar medium is proposed for the determination of novalgin. The method is based on the instantaneous formation of a red-orange product (lambda(max) = 510 nm) after the reaction between novalgin and p-dimethylaminocinnamaldehyde (p-DAC) in a dilute acid medium. The sensitivity of this reaction was increased by a factor of 5.6 in the presence of sodium dodecyl sulfate (SDS). Experimental design methodologies were used to optimize the chemical and FI variables. The calibration curve was linear in the range of 1.45 x 10(-6) to 2.90 x 10(-5) mol L(-1) with an excellent correlation coefficient (r = 0.9999). The detection limit was 1.31 x 10(-7) mol L(-1) (n = 20, RSD = 2.0%). No interferences were observed from the common excipients. The results obtained by the proposed method were favorably compared with those given by the iodometric reference method at 95% confidence level.     

Scaling laws and the modern city

The inter-relations and the complexity of modern urban spaces are difficult to analyse in a way that allows improving living conditions or help to ascertain optimal decisions for saving energy or improving sustainability. Carefully designed decisions and guidelines might produce unexpected results because of particularities, or complex sets of reactions from residents or economic counterparts. Complexity tends to increase with size, such as when, for instance, services tend to concentrate in large agglomerations, and transportation needs take on critical importance. Complex systems such as living organisms are known to follow approximate relationships as scaling laws between the variables that describe them. Some of these kinds of relationships are tested in relation to modern developed urban spaces, in which it is possible to find a reasonable continuity with the types of scales seen in living organisms, and some preliminary conclusions are drawn.     

Design,synthesis, evaluation,and molecular dynamic simulation of triclosan mimic diphenyl ether derivatives as antitubercular and antibacterial agents

In the present work, we have explored triclosan mimic diphenyl ether derivatives as inhibitors of Mycobacterium tuberculosis enoyl acyl carrier protein reductase (InhA) using a structure-based drug design approach. The virtual library of diphenyl ethers was designed and compounds with acceptable absorption, distribution, metabolism, excretion, and toxicity properties were docked. The compounds with higher dock score (5a-g) than triclosan were synthesized, characterized, and evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. Among the synthesized compounds, compounds 5f and 5c appeared to be the most promising with minimum inhibitory concentration of 18 μM and 36 μM respectively. The molecular dynamics simulation study of the most active compound 5f and triclosan was performed, which correlates with its activity in comparison with triclosan. All the compounds were further evaluated for cytotoxicity studies against Vero, and HepG2 were found to be safe. Furthermore, compound 5f was evaluated for in vitro cytotoxicity against mouse macrophage cell lines (RAW 264.7), and the study indicated its safety in eukaryotes at 50-μM concentration. In addition, compounds 5a-g were also screened for their in vitro antibacterial activity against two gram-positive and two gram-negative bacteria by resazurin-based microtiter dilution assay method. Among the synthesized compounds, 5f and 5b appeared to be promising, against various gram-positive and gram-negative microorganisms, indicating its broad-spectrum potential.

     

A Light‐Triggerable Nanoparticle Library for the Controlled Release of Non‐Coding RNAs

RNA‐based therapies offer a wide range of therapeutic interventions including the treatment of skin diseases; however, the strategies to efficiently deliver these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we report the synthesis of a triggerable polymeric nanoparticle (NP) library composed of 160 formulations, presenting physico‐chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500 %) than commercially available lipofectamine in gene‐knockdown activity. These formulations showed differential internalization by skin cells and the endosomal escape was rapid (minutes range). The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA‐150‐5p healed faster than wounds treated with scrambled miRNA. Light‐activatable NPs offer a new strategy to topically deliver non‐coding RNAs.     

Synthesis of All-Carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron-Catalyzed Kumada Cross-Coupling

1,3-Disubstituted bicyclo[1.1.1]pentanes (BCPs) are important motifs in drug design as surrogates for p-substituted arenes and alkynes. Access to all-carbon disubstituted BCPs via cross-coupling has to date been limited to use of the BCP as the organometallic component, which restricts scope due to the harsh conditions typically required for the synthesis of metallated BCPs. Here we report a general method to access 1,3-C-disubstituted BCPs from 1-iodo-bicyclo[1.1.1]pentanes (iodo-BCPs) by direct iron-catalyzed cross-coupling with aryl and heteroaryl Grignard reagents. This chemistry represents the first general use of iodo-BCPs as electrophiles in cross-coupling, and the first Kumada coupling of tertiary iodides. Benefiting from short reaction times, mild conditions, and broad scope of the coupling partners, it enables the synthesis of a wide range of 1,3-C-disubstituted BCPs including various drug analogues.     

Structural stability and electrochemical properties of Gd-doped ZrO2 nanoparticles prepared by sol–gel

Cubic, tetragonal and monoclinic Gd-doped zirconia nanoparticles with nominal composition Gd_xZr_1?xO₂ in the range 0 ≤ x ≤ 0.2, were prepared by annealing dried gels of Gd-containing zirconia at temperatures over the range between 450 and 1,300 °C. The synthesized zirconia-based nanoparticles with increased gadolinium load were characterized by X-ray powder diffraction, infrared and Raman spectroscopies, and transmission electron microscopy. The stabilization of the crystalline forms of Gd-doped ZrO₂ solid solutions depends on the amount of Gd dopant and the annealing temperature. For low Gd loads in Gd_xZr_1?xO₂ being x < 0.05, the tetragonal form is the single phase up to 1,100 °C, whereas the monoclinic is the crystalline form detected up to 1,300 °C. Within the range of compositions 0.05 ≤ x < 0.1, is the tetragonal the only stabilized zirconia crystalline structure over the whole range of temperature up to 1,300 °C. For higher Gd-contents, in the range 0.1 ≤ x ≤ 0.2, is the cubic zirconia form the only stable phase for the whole range of annealing temperatures. Solid-state electrochemistry of the gadolinium-doped zirconia performed by the voltammetry of microparticles approach allowed distinguishing different electrochemical answers of Gd cation associated with slightly different local coordination surrounding of cations. Enantioselective electrocatalytic effect of monoclinic Gd-doped ZrO₂ on the oxidation of l-(+)-tartaric acid and d-(?)-tartaric was also studied.