Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

RNA interference provides enormous potential for the treatment of several diseases, including cancer. Nevertheless, successful therapies based on siRNA require overcoming various challenges, such as poor pharmacokinetic characteristics of the small RNA molecule and inefficient cytosolic accumulation. In this respect, the development of functional siRNA carrier systems is a major task in biomedical research. To provide such a desired system, the synthesis of 3‐arm and 6‐arm PeptoStars is aimed for. The different branched polypept(o)idic architectures share a stealth‐like polysarcosine corona for efficient shielding and a multifunctional polylysine core, which can be independently varied in size and functionality for siRNA complexation‐, transport and intra cellular release. The special feature of star‐like polypept(o)ides is in their uniform small size (<20 nm) and a core–shell structure, which implies a high stability and stealth‐like properties and thus, they may combine long circulation times and a deep penetration of cancerous tissue. Initial toxicity and complement studies demonstrate well tolerated cationic PeptoStars with high complexation capability toward siRNA (N/P ratio up to 3:1), which can lead to potent RNAi for optimized systems. Here, the synthetic development of 3‐arm and 6‐arm polypept(o)idic star polymers, their modification with endosomolytic moieties, and first in vitro insights on RNA interference are reported on.     

Direct,oxidative halogenation of diaryl- or dialkylphosphine oxides with (dihaloiodo)arenes

The oxidative halogenation of diaryl- or dialkylphosphine oxides with the hypervalent iodine reagents (difluoroiodo)toluene (p-TolIF₂, 1) and (dichloroiodo)benzene (PhICl₂, 2) is reported. Phosphoric fluorides could be recovered in 32–75% yield, or they could be trapped with EtOH to give the corresponding phosphinate in typically good yield. Phosphoric chlorides were not readily isolable, and were trapped with alcohol and amine nucleophiles, giving diaryl- or dialkylphos-phinates and phosphinamides in up to 90% yield.     

Nitraza-/Oxa-Propylene- and Hydrazonemethylene-Bridged 1,2,4-Nitraminotriazoles and Selected Salts

Two new bridged nitraminotriazoles with bridging oxapropylene and nitrazapropylene moieties were synthesized, and converted into several salts, as well as from the hydrazonemethylene bridged nitraminotriazole. All compounds were fully characterized by NMR and IR spectroscopy, elemental analysis as well as differential thermal analysis. The sensitivity towards friction and impact were determined according to BAM standard technics and the energetic properties were calculated by using the EXPLO5 computer code. The neutral compounds as well as the various salts were examined in terms of their physicochemical properties and detonation performance to each other and compared to the commonly used secondary explosive RDX.     

Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.     

High-pressure phase transition of Bi2Fe4O9

The high-pressure behaviour of Bi2Fe4O9 was analysed by in situ powder and single-crystal x-ray diffraction and Raman spectroscopy. Pressures up to 34.3(8) GPa were generated using the diamond anvil cell technique. A reversible phase transition is observed at approximately 6.89(6) GPa and the high-pressure structure is stable up to 26.3(1) GPa. At higher pressures the onset of amorphization is observed. The crystal structures were refined from single-crystal data at ambient pressure and pressures of 4.49(2), 6.46(2), 7.26(2) and 9.4(1) GPa. The high-pressure structure is isotypic to the high-pressure structure of Bi2Ga4O9. The lower phase transition pressure of Bi2Fe4O9 with respect to that of Bi2Ga4O9 (16 GPa) confirms the previously proposed strong influence of cation substitution on the high-pressure stability and the misfit of Ga3+ and Fe3+ in tetrahedral coordination at high pressure. A fit of a second-order Birch–Murnaghan equation of state to the p–V data results in K0 = 74(3) GPa for the low-pressure phase and K0 = 79(2) GPa for the high-pressure phase. The mode Grüneisen parameters were obtained from Raman-spectroscopic measurements.     

Conversion of Waste Tyres into Carbon Black and their Utilization as Adsorbent

Pyrolysis has the potential of transforming used tyres into useful recyclable products. Pyrolytic carbon black is one of the most important products of tyre pyrolysis. Waste tyres were pyrolysed at 450 °C in a batch reactor under atmospheric pressure. The recovered pyrolytic carbon black residues were studied to investigate their characteristics for use as a possible adsorbent. EDX elemental analysis and surface area determinations were used to investigate the distinctive features of pyrolytic carbon black. Due to various inorganic additives of the original tyre that contaminated the carbon black obtained, it was treated with acid for demineralization. The demineralized carbon black was activated at 900 °C in a furnace. It was observed that acid treatment and activation increased the surface areas and decreased the concentration of contaminants. Furthermore, adsorption characteristics of methylene blue on acid‐treated and activated carbon black (prepared via acid treatment) were compared with those of commercial activated carbon in liquid phase adsorption. It was found that adsorption capacity of methylene blue on acid‐treated activated carbon black was greater.     

Determination of Furosemide by Simple Diazotization Method in Pharmaceutical Preparations

A simple and rapid spectrophotometric method has been investigated for the determination of furosemide. The method is based upon simple diazotization reaction. The absorbance was measured at 480 nm. The method is optimized for acidity, amount of reagents required and heating time. The range of linearity was 0.4–10 μg mL^?1 of furosemide with molar absorptivity of 1.0 × 10⁴ l mol^?1 cm^?1. Standard deviation, coefficient of variance, limit of detection and limit of quantification were calculated using authentic standard of furosemide and were found to ± 0.0013,12.7%, 0.16 ppm and 0.52 ppm, respectively. The method was applied to various pharmaceutical preparations containing furosemide. The results of the investigated method for furosemide were compared with available official literature method. The results obtained by the proposed method agree well with the standard established method.