Search Results (17)

Here, the optical properties of the Nafion polymer membrane containing colloidal CdSe/CdS/ZnS nanocrystals embedded by diffusion have been studied. The CdSe/CdS/ZnS nanocrystals have a core/shell/shell appearance. All experiments were carried out at room temperature (22 ± 2) °C. A toluene solution was used to provide mobility to the active sulfone groups of the Nafion membrane and to embed the nanocrystals inside the membrane. The diffusion process of colloidal CdSe/CdS/ZnS nanocrystals into Nafion proton exchange membrane has resulted in a new molecular complex “Nafion–colloidal CdSe/CdS/ZnS nanocrystals”. The kinetics of the nanocrystals embedding into the membrane matrix was investigated using luminescence analysis and absorption spectroscopy techniques. The embedding rate of CdSe/CdS/ZnS nanocrystals into the Nafion polymer membrane was approximately 4·10⁻³ min⁻¹. The presence of new luminescence centers in the membrane was proved independently by laser emission spectroscopy. The luminescence spectrum of the resulting molecular complex contains intensity maxima at wavelengths of 538, 588, 643 and 700 nm. The additional luminescence maximum observed at the 643 nm wavelength was not recorded in the original membrane, solvent or in the spectrum of the semiconductor nanoparticles. The luminescence maximum of the colloidal CdSe/CdS/ZnS nanocrystals was registered at a wavelength of 634 nm. The intensity of the luminescence spectrum of the membrane with embedded nanocrystals was found to be higher than the intensity of the secondary emission peak of the initial nanocrystals, which is important for the practical use of the “Nafion–colloidal nanocrystals” complex in optical systems. The lines contained in the luminescence spectrum of the membrane, which has been in solution with colloidal nanocrystals for a long time, registered upon its drying, show the kinetics of the formation of the molecular complex “Nafion membrane–nanocrystals”. Colloidal nanocrystals located in the Nafion matrix represent an analog of a luminescent transducer. Full article

This study proposed a high-performance thin-layer chromatography (HPTLC) screening method to detect phosphodiesterase 5 (PDE-5) inhibitors as possible adulterant agents in various dietary supplements. Chromatographic analysis was performed on silica gel 60F254 plates using a mixture of ethyl acetate:toluene:methanol:ammonia in a volume ratio of 50:30:20:0.5 as a mobile phase. The system provided compact spots and symmetrical peaks of sildenafil and tadalafil with retardation factor values of 0.55 and 0.90, respectively. The analysis of products purchased from the internet or specialized stores demonstrated the presence of sildenafil, tadalafil, or both compounds in 73.3% of products, highlighting inadequacies and inconsistencies in the labeling, as all dietary supplements were declared to be natural. The results were confirmed using ultra-high-performance liquid chromatography coupled with a positive electrospray ionization high-resolution tandem mass spectrometry (UHPLC-HRMS-MS) method. Furthermore, in some samples, vardenafil and various analogs of PDE-5 inhibitors were detected using a non-target HRMS-MS approach. The results of the quantitative analysis revealed similar findings between the two methods, with adulterant quantities found to be similar to or higher than those in approved medicinal products. This study demonstrated that the HPTLC method is a suitable and economical method for screening PDE-5 inhibitors as adulterants in dietary supplements intended for sexual activity enhancement. Full article

The efficiency of the removal of Cs-137 radionuclides with porous and non-porous resorcinol–formaldehyde resins from alkaline solutions simulating the composition of real liquid radioactive waste (LRW) streams has been evaluated. Resins were synthesized through the polycondensation of resorcinol and formaldehyde in an alkaline medium at a molar ratio of 1.8/2.2 and a temperature of 210 °C. The Cs-137 distribution coefficients on RFRs in alkaline solutions simulating LRW were above 10³ mL/g under static sorption conditions. In a model solution with pH 11, the full dynamic sorption capacity of non-porous RFR was 0.178 mmol/g. The values of the full dynamic sorption capacities of porous RFRs were 0.274 and 1.035 mmol/g for resins obtained with calcium carbonate and toluene as templates, respectively. When the sizes of RFR beads increased two-fold, the volume until 5% cesium breakthrough decreased by 20–40%. The most pronounced beneficial effect of the RFR’s porosity was observed at flow rates from 25 to 50 BV/h. It was shown that the negative effect of metal cations on Cs-137 uptake increases in the following order: Na⁺ < Mg²⁺ < Ca²⁺ < K⁺. The number of bed volumes of LRW-simulating solution decontaminated with RFRs until 5% cesium breakthrough was above 450; that is higher than the value of known commercially available analogs. The latter shows that the developed RFRs are promising for application in technological schemes of alkaline LRW processing. Full article

Co₃O₄, MgCo₂O₄ and MgO materials have been synthesized using a simple co-precipitation approach and systematically characterized. The total conversion of toluene to CO₂ and H₂O over spinel MgCo₂O₄ with wormlike morphology has been investigated. Compared with single metal oxides (Co₃O₄ and MgO), MgCo₂O₄ with the highest activity has exhibited almost 100% oxidation of toluene at 255 °C. The obtained results are analogous to typical precious metal supported catalysts. The activation energy of toluene over MgCo₂O₄ (38.5 kJ/mol) is found to be much lower than that of Co₃O₄ (68.9 kJ/mol) and MgO ((87.8 kJ/mol)). Compared with the single Co and Mg metal oxide, the as-prepared spinel MgCo₂O₄ exhibits a larger surface area, highest absorbed oxygen and more oxygen vacancies, thus highest mobility of oxygen species due to its good redox capability. Furthermore, the samples specific surface area, low-temperature reducibility and surface adsorbed oxygenated species ratio decreased as follows: MgCo₂O₄ > Co₃O₄ > MgO; which is completely in line with the catalytic performance trends and constitute the reasons for MgCo₂O₄ high excellent activity towards toluene total oxidation. The overall finding supported by ab initio molecular dynamics simulations of toluene oxidation on the Co₃O₄ and MgCo₂O₄ suggest that the catalytic process follows a Mars–van Krevelen mechanism. Full article

The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N-indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels–Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC₅₀ 1–8 μM) and two of them (compounds 6 and 14) showed a good selectivity index. Full article

A novel curcumin analog namely 2-chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]-styryl}pyrimidine (compound 7) was synthesized by three-step reaction. The condensation reaction of protected vanillin with 2-chloro-4,6-dimethylpyrimidine (6) was the most efficient step, resulting in a total yield of 72%. The characterization of compound 7 was performed by ¹H and ¹³C nuclear magnetic resonance (NMR), as well as high-resolution mass spectrometry. The experimental spectrometric data were compared with the theoretical spectra obtained by the density functional theory (DFT) method, showing a perfect match between them. UV-visible spectroscopy and steady-state fluorescence emission studies were performed for compound 7 in solvents of different polarities and the results were correlated with DFT calculations. Compound 7 showed a solvatochromism effect presenting higher molar extinction coefficient (log ε = 4.57) and fluorescence quantum yield (ϕ = 0.38) in toluene than in acetonitrile or methanol. The simulation of both frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) suggested that the experimental spectra profile in toluene was not interfered by a possible charge transfer. These results are an indication of a low probability of compound 7 in reacting with unsaturated phospholipids in future applications as a fluorescent dye in biological systems. Full article

The rate of hydrolysis–condensation reaction of phenyltrichlorosilane in water-acetone solutions and the product yields were shown to significantly depend on the concentration of HCl (C_HCl) in the solutions. The main product of the reaction was all-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane. This was different from the earlier published results of analogous reactions of m-tolylSiCl₃, m-ClPhSiCl₃, and α-naphtylSiCl, in which some products of other types were formed. For example, trans-1,1,3,3-tetrahydroxy-1,3-di-α-naphtyldisiloxane was obtained in the case of α-naphtylSiCl₃. All-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane was treated in acetone with HCl to give the other three geometric isomers (cis-cis-trans-, cis-trans-, and all-trans-). The thermal self-condensation of these four isomers under “pseudo”-equilibrium conditions (under atmospheric pressure) was investigated in different solvents, in quartz or molybdenum glass flasks. The compositions of the products were monitored by APCI-MS and ²⁹Si NMR spectroscopy. It was shown that all-cis- and cis-cis-trans-isomers in toluene or anisole mostly gave the cage-like Ph-T_8,10,12,14 and uncompleted cage-like Ph-T_10,12OSi(HO)Ph compounds. In contrast to these two isomers, the cis-trans–isomer in toluene mainly formed dimers with the loss of one or two molecules of water. However, in acetonitrile, significant amounts of Ph-T_10,12 and Ph-T_10,12OSi(HO)Ph species were formed along with the dimers. All-trans-isomer did not enter into the reaction at all. Full article

The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies. Full article

Ruthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. This report deals with the reaction between dihydride ruthenium mer-[Ru(H)₂(CO)(PPh₃)₃], 1 and the thymine acetic acid (THAcOH) selected as model for nucleobase derivatives. The reaction in refluxing toluene between 1 and THAcOH excess, by H₂ release affords the double coordinating species κ¹-(O)THAc-, κ²-(O,O)THAc-[Ru(CO)(PPh₃)₂], 2. The X-ray crystal structure confirms a simultaneous monohapto, dihapto- THAc coordination in a reciprocal facial disposition. Stepwise additions of THAcOH allowed to intercept the monohapto mer-κ¹(O)THAc-Ru(CO)H(PPh₃)₃] 3 and dihapto trans_(P,P)-κ²(O,O)THAc-[Ru(CO)H(PPh₃)₂] 4 species. Nuclear magnetic resonance (NMR) studies, associated with DFT (Density Function Theory)-calculations energies and analogous reactions with acetic acid, supported the proposed reaction path. As evidenced by the crystal supramolecular hydrogen-binding packing and ¹H NMR spectra, metal coordination seems to play a pivotal role in stabilizing the minor [(N=C(OH)] lactim tautomers, which may promote mismatching to DNA nucleobase pairs as a clue for its anticancer activity. Full article

Analysis of amino acids by gas chromatography-mass spectrometry (GC–MS) requires at least one derivatization step to enable solubility in GC–MS-compatible water-immiscible organic solvents such as toluene, to make them volatile to introduce into the gas chromatograph and thermally stable enough for separation in the GC column and introduction into the ion-source, and finally to increase their ionization by increasing their electronegativity using F-rich reagents. In this work we investigated the long-term stability of the methyl esters pentafluoropropionic (Me-PFP) derivatives of 21 urinary amino acids prepared by a two-step derivatization procedure and extraction by toluene. In situ prepared trideuteromethyl ester pentafluoropropionic derivatives were used as internal standards. GC–MS analysis (injection of 1 µL aliquots and quantification by selected-ion monitoring of specific mass fragments) was performed on days 1, 2, 8, and 15. Measured peak areas and calculated peak area ratios were used to evaluate the stability of the derivatives of endogenous amino acids and their internal standards, as well as the precision and the accuracy of the method. All analyses were performed under routine conditions. Me-PFP derivatives of endogenous amino acids and their stable-isotope labelled analogs were stable in toluene for 14 days. The peak area values of the derivatives of most amino acids and their internal standards were slightly higher on days 8 and 15 compared to days 1 and 2, yet the peak area ratio values of endogenous amino acids to their internal standards did not change. Our study indicates that Me-PFP derivatives of amino acids from human urine samples can easily be prepared, are stable at least for 14 days in the extraction solvent toluene, and allow for precise and accurate quantitative measurements by GC–MS using in situ prepared deuterium-labelled methyl ester as internal standard. Full article

Anthraquinones (yellow dyes) were extracted from Japanese knotweed rhizomes with twelve extraction solvents (water; ethanol_(aq) (20%, 40%, 60%, 70% and 80%), ethanol, 70% methanol_(aq), methanol, 70% acetone_(aq), acetone and dichloromethane). The obtained sample test solutions (STSs) were analyzed using high-performance thin-layer chromatography (HPTLC) coupled to densitometry and mass spectrometry (HPTLC–MS/MS) on HPTLC silica gel plates. Identical qualitative densitometric profiles (with anthraquinone aglycones and glycosylated anthraquinones) were obtained for STSs in all the solvents except for the STS in dichloromethane, which enabled the most selective extractions of anthraquinone aglycones emodin and physcion. The highest extraction efficiency, evaluated by comparison of the total peak areas in the densitograms of all STSs scanned at 442 nm, was achieved for 70% acetone_(aq). In STS prepared with 70% acetone_(aq), the separation of non-glycosylated and glycosylated anthraquinones was achieved with developing solvents toluene–acetone–formic acid (6:6:1, 3:6:1 and 3:3:1 v/v) and dichloromethane–acetone–formic acid (1:1:0.1, v/v). Non-glycosylated anthraquinones were separated only with toluene–acetone–formic acid, among which the best resolution between emodin and physcion gave the ratio 6:6:1 (v/v). This solvent and dichloromethane–acetone–formic acid (1:1:0.1, v/v) enabled the best separation of glycosylated anthraquinones. Four HPTLC-MS/MS methods enabled the identification of emodin and tentative identification of its three glycosylated analogs (emodin-8-O-hexoside, emodin-O-acetyl-hexoside and emodin-O-malonyl-hexoside), while only the HPTLC-MS/MS method with toluene-acetone-formic acid (6:6:1, v/v) enabled the identification of physcion. Changes of the shapes and the absorption maxima (bathochromic shifts) in the absorption spectra after post-chromatographic derivatization provided additional proof for the detection of physcion and rejection of the presence of chrysophanol in STS. Full article

PF-543, the most potent sphingosine kinase (SK) inhibitor, does not demonstrate effective anticancer activity in some cancer cells, unlike other known SK1 inhibitors. PF-543 has a non-lipid structure with a unique toluene backbone; however, the importance of this structure remains unclear. Therefore, the purpose of this study was to investigate changes in SK inhibitory and anticancer activities and to explore the role of the tolyl group structure of PF-543 through various modifications. We transformed the methyl group of PF-543 into hydrogen, fluorine, and hydroxy. PF-543 derivatives in which the methyl group was substituted by hydrogen and fluorine (compound 5) demonstrated SK1 inhibitory and anticancer activities similar to PF-543. Moreover, we performed molecular modeling studies of PF-543 and compound 5. To assess the metabolic stability of PF-543 and compound 5, we determined their degree of degradation using the liver microsomes of four different animal species (human, dog, rat, and mouse). However, both PF-543 and compound 5 showed poor microsomal stability. Therefore, for the medical applications of PF-543, the structural modifications of its other parts may be necessary. Our results provide important information for the design of additional PF-543 analogs. Full article

In this study, N-methylated analogs of hot-spots of insulin were designed and synthesized, in the expectation that they would inhibit the aggregation of both insulin hot-spots and the entire hormone. Synthesis of insulin “amyloidogenic” analogs containing N-methylated amino acid residues was performed by microwave-assisted solid phase according to the Fmoc/tert-Bu strategy. As a coupling reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO^-) was used. Three independent methods were applied in aggregation studies of the complexes of insulin with its N-methylated peptides. Additionally, circular dichroism (CD) measurements were used to confirm that aggregation processes did not occur in the presence of the N-methylated analogs of hot-spot insulin fragments, and that insulin retains its native conformation. Of the seven N-methylated analogs of the A- and B-chain hot-spots of insulin, six inhibited insulin aggregation (peptides 1 and 3–7). All tested peptides were found to have a lower ability to inhibit the aggregation of insulin hot-spots compared to the capability to inhibit native hormone aggregation. Full article

Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli—Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe³⁺, which makes them suitable candidates for the above-mentioned applications. Full article

An efficient and facile general method for the synthesis of conduritol C analogs, taking advantage of an enantioselective biocatalysis process of monosubstituted benzenes, is described. The absolute stereochemical patterns of the target molecules (−)-conduritol C, (−)-bromo-conduritol C, and (−)-methyl-conduritol C were achieved by means of chemoenzymatic methods. The stereochemistry present at the homochiral cyclohexadiene-cis-1,2-diols derived from the arene biotransformation and the enantioselective ring opening of a non-isolated vinylepoxide derivative permitted the absolute configuration of the carbon bearing the hydroxyl groups at the target molecules to be established. All three conduritols and two intermediates were crystallized, and their structures were confirmed by X-ray diffraction. The three conduritols and intermediates were isostructural. The versatility of our methodology is noteworthy to expand the preparation of conduritol C analogs starting from toluene dioxygenase (TDO) monosubstituted arene substrates. Full article