Dithiolane quartets: thiol-mediated uptake enables cytosolic delivery in deep tissue

The cytosolic delivery of various substrates in 3D multicellular spheroids by thiol-mediated uptake is reported. This is important because most orthodox systems, including polycationic cell-penetrating peptides, fail to deliver efficiently into deep tissue. The grand principles of supramolecular chemistry, that is the pH dependence of dynamic covalent disulfide exchange with known thiols on the transferrin receptor, are proposed to account for transcytosis into deep tissue, while the known but elusive exchange cascades along the same or other partners assure cytosolic delivery in kinetic competition. For quantitative detection in the cytosol, the 2D chloroalkane penetration assay (CAPA) is translated to 3D deep tissue. The targeted delivery of quantum dots, otherwise already troublesome in 2D culture, and the controlled release of mechanophores are realized to exemplify the power of thiol-mediated uptake into spheroids. As transporters, dithiolane quartets on streptavidin templates are introduced as modular motifs. Built from two amino acids only, the varied stereochemistry and peptide sequence are shown to cover maximal functional space with minimal structural change, i.e., constitutional isomers. Reviving a classic in peptide chemistry, this templated assembly of β quartets promises to expand streptavidin biotechnology in new directions, while the discovery of general cytosolic delivery in deep tissue as an intrinsic advantage further enhances the significance and usefulness of thiol-mediated uptake.

Cytosolic delivery in multicellular 3D spheroids is shown to be an intrinsic advantage of thiol-mediated uptake, which is compatible with proteins and QDs, achieving targeting and controlled release.     

A linear semi-infinite programming strategy for constructing optimal wavelet transforms in multivariate calibration problems

A novel strategy for the optimization of wavelet transforms with respect to the statistics of the data set in multivariate calibration problems is proposed. The optimization follows a linear semi-infinite programming formulation, which does not display local maxima problems and can be reproducibly solved with modest computational effort. After the optimization, a variable selection algorithm is employed to choose a subset of wavelet coefficients with minimal collinearity. The selection allows the building of a calibration model by direct multiple linear regression on the wavelet coefficients. In an illustrative application involving the simultaneous determination of Mn, Mo, Cr, Ni, and Fe in steel samples by ICP-AES, the proposed strategy yielded more accurate predictions than PCR, PLS, and nonoptimized wavelet regression.     

Development of a synthetic route towards N4,N9-disubstituted 4,9-diaminoacridines: On the way to multi-stage antimalarials

A multi-step synthetic route towards N⁴,N⁹-disubstituted 4,9-diaminoacridines that, to the best of our knowledge, has no precedence in the literature, has been developed. The target structures are likely to reveal interesting biological activities in the near future, not only due to their mepacrine-like core, but also because they embed simultaneously the pharmacophores of chloroquine and primaquine, antimalarial drugs that act at different stages of malaria infection.     

Exposure risk assessment of uranium intake of the milk products from the region of Pernambuco,Brazil

Journal of Radioanalytical and Nuclear Chemistry - Haloperidol (HP) is a dopamine blocking agent. HP was radiolabeled with 125I using direct electrophilic substitution. Different HP formulations...     

A fluorescence toolbox: A review of investigation of electrophoretic separations,process, and interfaces

This review focuses on fluorescence spectroscopy techniques for the investigation of electrophoretic separations. Fluorescence has been used as a sensitive detector for capillary, gel, and microchip electrophoresis for decades. However, advanced fluorescence methods can be used to study transport, interfacial phenomena, intermolecular and affinity interactions, and other processes that occur during separation. This so‐called spectroscopic toolkit can be implemented to understand fundamental behavior in electrophoresis and electrokinetic chromatography. Techniques such as fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and fluorescence anisotropy are discussed in relation to electrophoretic separations. Newer methods such as super‐resolution microscope are also introduced.     

Synthesis and characterization of thiosemicarbazone derivatives of 2-ethoxy-3-methoxy-benzaldehyde and their rhenium(I) complexes

The ligands (HL¹, HL² and HL³) have been prepared and their reaction with fac-[ReX(CO)₃(CH₃CN)₂] (X = Br, Cl) in chloroform gave the adducts [ReX(CO)₃(HL)] (1a X = Cl, R = H; 1a′ X = Br, R = H; 1b X = Cl, R = CH₃; 1b′ X = Br, R = CH₃; 1c X = Cl, R = Ph; 1c′ X = Br, R = Ph) in good yield. All the compounds have been characterized by elemental analysis, mass spectrometry (FAB), IR and ¹H NMR spectroscopic methods, and the structures of the ligands have been elucidated by X-ray diffraction. In the case of HL¹, we have tried the reaction with [ReX(CO)₅] (X = Br, Cl) in toluene and we proved the formation of the adduct also by this way by the isolation of single crystals of 1a′ · ½C₇H_8.     

Spectrophotometric determination of zinc in copper-base alloys with TAN

TAN reacts with zinc(II) forming a red complex with composition 1:2 Zn(II)-TAN and absorption maximum at 582 nm. Zinc can be determined with this reagent in the presence of Triton X-100, in the pH range 6.20-8.00 with a molar absorptivity of 4.5×10⁴ l/mol/cm Beer's Law was obeyed up to least 1.55 g/ml. Copper interference was eliminated with a mixture of thiosulfate and ascorbic acid and nickel separated by precipitation with dimethylglyoxime. The proposed method was used for zinc determination in several copper-base alloys and the results of analysis in comparison with certified values indicated that the procedure was accurate and precise. A derivative procedure is also proposed, allowing zinc determination with high sensitivity (5-400 ng/ml).     

A cryosolution infrared study of the complexes of fluoroform with ammonia and pyridine: Evidence for a C-H...N pseudo blue-shifting hydrogen bond

Mid-infrared spectra of mixed solutions in liquid xenon containing fluoroform and either ammonia or pyridine have been investigated at temperatures between 173 and 213 K. For both Lewis bases, a new band is found in the CH stretching region at a frequency approximately 5 cm(-1) higher than that of monomer fluoroform, which is assigned to a complex between fluoroform and the Lewis base. A detailed analysis of the nu1/2nu(4) Fermi resonance in the proton donor shows that the blue shifts observed for the complexes are not caused by a strengthening of the CH bond during the complexation, but are due to the changes in the Fermi resonance interactions. Information on the nu1/2nu(4) Fermi resonance was also obtained for the complexes of fluoroform with dimethyl ether and trimethyl amine.     

Antioxidant, Anti-inflammatory, and Hypoglycemic Effects of the Leaf Extract from Passiflora nitida Kunth

Diabetes mellitus is a metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as insulin resistance, obesity, hyperlipidemia, and hypertension, also with alterations in the immune and neuronal systems. Brazilian plants have been studied as important sources for new molecules with medicinal properties. The genus Passiflora known as “Maracujá” has been used as a traditional folk medicine for a long time, so an investigation was performed regarding an endemic kind of passion fruit (Passiflora nitida Kunth) from Amazonas, Brazil. Here, we aimed to determine its potential biological activity against metabolic syndrome, oxidative stress, pain, and inflammation. The hydroethanol leaf extract revealed an in vitro α-glucosidase inhibitory activity of 50 % inhibitory concentration (IC₅₀)?=?6.78?±?0.31 μg/mL and an α-amylase inhibition of IC₅₀?=?93.36?±?4.37. In vivo, experiments of different saccharide tolerance resulted in significant glycemia control and, with alloxan-diabetic mice, resulted in a decrease of total cholesterol, a hypoglycemic effect, and an antioxidant activity by thiobarbituric acid-reactive substances measurement. Also, it decreased the carrageenan-induced edema volume and the rate of writhing as a nociceptive response. These results indicate positive effects of P. nitida extract and its potential to inhibit metabolic syndrome.     

Comparative study of the oxidative and thermal stability of vegetable oils to be used as lubricant bases

Demand for lubricating oils is increasing in the growing Brazilian economy. The use of vegetable bases in exchange of minerals can bring socio-economic and environmental benefits for Brazil. The purpose of this study is to compare the thermal and oxidative stability of vegetable oils related to the bases commonly used as lubricants. In this study, thermogravimetric analysis of castor oil, cotton oil, macauba’s almond oil, passion oil, paraffinic mineral oil, naphthenic oil (NH-140) and synthetic oil (Etro) was performed in inert and oxidative atmosphere to study the thermal and oxidative degradation of the vegetable oils related to the most common lubricants’ oils base. These oils’ oxidation stability were determined by standard procedures (ISO 6886). The use of mineral oil’s additives in these vegetable oils was tested to verify the viability of these additives to improve the oxidative stability of the vegetable oils. The castor oil and the cotton oil presented results of thermal analysis similar to the mineral and synthetic bases values. The castor oil was the only vegetable oil that showed a great oxidative stability. All other vegetable oils had their oxidative stability significantly increased by the additives.