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Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects. To overcome DOX limitations, two novel pyridoxine-derived doxorubicin derivatives were synthesized (DOX-1 and DOX-2). In the present study, their antitumor activity and mechanism of action were investigated. Of these two compounds, DOX-2, in which the pyridoxine fragment is attached to the doxorubicin molecule via a C3 linker, revealed higher selectivity against specific cancer cell types compared to doxorubicin and a promising safety profile for conditionally normal cells. However, the compound with a C1 linker (DOX-1) was not characterized by selectivity of antitumor action. It was revealed that DOX-2 obstructs cell cycle progression, induces apoptosis via the mitochondrial pathway without the development of necrosis, and showcases antioxidant capabilities, underlining its cell-regulatory roles. In contrast to doxorubicin's DNA-centric mechanism, DOX-2 does not interact with nuclear DNA. Given these findings, DOX-2 presents a new promising direction in cancer therapeutics, which is deserving of further in vivo exploration.
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The main object of this work was to characterize the structure and properties of laboratory-made fish gelatin from cod skin in comparison with known commercial gelatins of fish and mammalian origin. This is one way we can contribute to the World Food Program and characterize foodstuff resources from alternative natural sources. Our research was based on the combination of an expanded set of complementary physical-chemical methods to study the similarities and distinctions of hydrogels from traditional and novel gelatin sources from underused marine resources. In this work, we have compared the morphology, supramolecular structure and colloid properties of two commercial (mammalian and fish) gelatins with gelatin we extracted from cold-water cod skin in laboratory conditions. The obtained results are novel, showing that our laboratory-produced fish gelatin is much closer to the mammalian one in terms of such parameters as thermal stability and strength of structural network under temperature alterations. Especially interesting are our experimental observations comparing both fish gelatins: it was shown that the laboratory-extracted cod gelatin is essentially more thermally stable compared to its commercial analogue, being even closer in its rheological properties to the mammalian one.
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We report herein the design, synthesis and biological evaluation of series of 7-substituted fluoroquinolones with pyridoxine derivatives. In vitro screening of antibacterial activity and toxicity of 39 synthesized fluoroquinolones defined compounds 7 and 28 as lead compounds for further investigations. On various clinical isolates lead compounds 7 and 28 exhibited antibacterial activity comparable with reference fluoroqinolones. Mutagenic effects haven't been observed for these compounds in SOS-chromotest. Compound 7 are non-toxic in vivo on mice (LD50 > 2000 mg/kg, oral) and rats (LD50 > 2000 mg/kg, oral). Compound 28 was more toxic (LD50 = 474 mg/kg, oral, mice). Moreover compound 7 showed greater in vivo efficacy compared to ciprofloxacin in a murine model of staphylococcal sepsis. Taken together the described active compound are promising candidate for preclinical trials.
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Fluoroquinolonas , Piridoxina , Ratones , Ratas , Animales , Fluoroquinolonas/farmacología , Piridoxina/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , CiprofloxacinaRESUMEN
Two-dimensional black phosphorus (BP) has emerged as a perspective material for various micro- and opto-electronic, energy, catalytic, and biomedical applications. Chemical functionalization of black phosphorus nanosheets (BPNS) is an important pathway for the preparation of materials with improved ambient stability and enhanced physical properties. Currently, the covalent functionalization of BPNS with highly reactive intermediates, such as carbon-free radicals or nitrenes, has been widely implemented to modify the material's surface. However, it should be noted that this field requires more in-depth research and new developments. Herein, we report for the first time the covalent carbene functionalization of BPNS using dichlorocarbene as a functionalizing agent. The P-C bond formation in the obtained material (BP-CCl2) has been confirmed by Raman, solid-state 31P NMR, IR, and X-ray photoelectron spectroscopy methods. The BP-CCl2 nanosheets exhibit an enhanced electrocatalytic hydrogen evolution reaction (HER) performance with an overpotential of 442 mV at -1 mA cm-2 and a Tafel slope of 120 mV dec-1, outperforming the pristine BPNS.
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Two-dimensional black phosphorus (BP) has attracted great attention as a perspective material for various applications. The chemical functionalization of BP is an important pathway for the preparation of materials with improved stability and enhanced intrinsic electronic properties. Currently, most of the methods for BP functionalization with organic substrates require either the use of low-stable precursors of highly reactive intermediates or the use of difficult-to-manufacture and flammable BP intercalates. Herein we report a facile route for simultaneous electrochemical exfoliation and methylation of BP. Conducting the cathodic exfoliation of BP in the presence of iodomethane makes it possible to generate highly active methyl radicals, which readily react with the electrode's surface yielding the functionalized material. The covalent functionalization of BP nanosheets with the P-C bond formation has been proven by various microscopic and spectroscopic methods. The functionalization degree estimated by solid-state 31P NMR spectroscopy analysis reached 9.7%.
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Comercio , Procesamiento Proteico-Postraduccional , Metilación , Electrodos , FósforoRESUMEN
Self-diffusion of ions in the protic ionic liquid ethylammonium nitrate (EAN) was studied by 1H NMR pulsed field gradient techniques between 294 and 393 K in the presence of a PTFE insert in a 5-mm NMR tube. At all temperatures, the bulk diffusion of ions (measured by 1H and 15N NMR) can be described by a unique diffusion coefficient. The presence of solid hydrophobic surfaces of PTFE induces regions of EAN in their vicinity, where diffusion of ions, both cations and anions, is reduced compared to the bulk values. An additional line-shape analysis in 1H NMR spectra showed that local mobility of ethylammonium cations in the surface layers near PTFE is also reduced.
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Líquidos Iónicos , Compuestos de Amonio Cuaternario , Difusión , Líquidos Iónicos/química , Politetrafluoroetileno , Compuestos de Amonio Cuaternario/químicaRESUMEN
Today, the synthesis of biocompatible and bioresorbable composite materials such as "polymer matrix-mineral constituent," which stimulate the natural growth of living tissues and the restoration of damaged parts of the body, is one of the challenging problems in regenerative medicine. In this study, composite films of bioresorbable polymers of polyvinylpyrrolidone (PVP) and sodium alginate (SA) with hydroxyapatite (HA) were obtained. HA was introduced by two different methods. In one of them, it was synthesized in situ in a solution of polymer mixture, and in another one, it was added ex situ. Phase composition, microstructure, swelling properties and biocompatibility of films were investigated. The crosslinked composite PVP-SA-HA films exhibit hydrogel swelling characteristics, increasing three times in mass after immersion in a saline solution. It was found that composite PVP-SA-HA hydrogel films containing HA synthesized in situ exhibited acute cytotoxicity, associated with the presence of HA synthesis reaction byproducts-ammonia and ammonium nitrate. On the other hand, the films with HA added ex situ promoted the viability of dental pulp stem cells compared to the films containing only a polymer PVP-SA blend. The developed composite hydrogel films are recommended for such applications, such as membranes in osteoplastic surgery and wound dressing.
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Ionic liquids (ILs) composed of tetra(n-butyl)phosphonium [P4444]+ and tetra(n-butyl)ammonium [N4444]+ cations paired with 2-furoate [FuA]-, tetrahydo-2-furoate [HFuA]-, and thiophene-2-carboxylate [TpA]- anions are prepared to investigate the effects of electron delocalization in anion and the mutual interactions between cations and anions on their physical and electrochemical properties. The [P4444]+ cations-based ILs are found to be liquids, while the [N4444]+ cations-based ILs are semi-solids at room temperature. Thermogravimetric analysis revealed higher decomposition temperatures and differential scanning calorimetry analysis showed lower glass transition temperatures for phosphonium-based ILs than the ammonium-based counterparts. The ILs are arranged in the decreasing order of their ionic conductivities as [P4444][HFuA] (0.069 mS cm-1) > [P4444][FuA] (0.032 mS cm-1) > [P4444][TpA] (0.028 mS cm-1) at 20 °C. The oxidative limit of the ILs followed the sequence of [FuA]-> [TpA]-> [HFuA]-, as measured by linear sweep voltammetry. This order can be attributed to the electrons' delocalization in [FuA]- and in [TpA]- aromatic anions, which has enhanced the oxidative limit potentials and the overall electrochemical stabilities.
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Here, we investigate the physicochemical and electrochemical properties of fluorine-free ionic liquid (IL)-based electrolytes with two different cations, tetrabutylphosphonium, (P4,4,4,4)+, and tetrabutylammonium, (N4,4,4,4)+, coupled to a new anion, 2-[2-(2-methoxyethoxy)ethoxy]acetate anion (MEEA)-, for both neat and (P4,4,4,4)(MEEA) also doped with 10-40 mol % of Li(MEEA). We find relatively weaker cation-anion interactions in (P4,4,4,4)(MEEA) than in (N4,4,4,4)(MEEA), and for both ILs, the structural flexibility of the oligoether functionality in the anion results in low glass transition temperatures, also for the electrolytes made. The pulsed field gradient nuclear magnetic resonance (PFG NMR) data suggest faster diffusion of the (MEEA)- anion than (P4,4,4,4)+ cation in the neat IL, but the addition of a Li salt results in slightly lower mobility of the former than the latter and lower ionic conductivity. This agrees with the combined 7Li NMR and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy data, which unambiguously reveal preferential interactions between the lithium cations and the carboxylate groups of the IL anions, which also increased as a function of the lithium salt concentration. In total, these systems provide a stepping stone for further design of fluorine-free and low glass transition temperature IL-based electrolytes and also stress how crucial it is to control the strength of ion-ion interactions.
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Some ionic liquids (ILs) change their dynamic properties when placed in a confinement between polar surfaces (Filippov et al., Phys. Chem. Chem. Phys. 2018, 20, 6316). The diffusivities of ions and NMR relaxation times in these ILs also reversibly change under a strong static magnetic field. The mechanisms of these phenomena are not clear, but it has been suggested that they involve modified hydrogen-bonding networks formed in these ILs in the presence of polar surfaces. To obtain a better understanding of these effects, we performed temperature-dependent measurements of chemical shifts and diffusion coefficients for ethylammonium nitrate (EAN) IL in the bulk phase (IB) and confined in layers with a thickness of ~4 µm between quartz plates unexposed (I phase) and exposed (IMF phase) to a static magnetic field of 9.4 T. It was shown that the NMR chemical shift of NH3 protons of EAN in the I phase is strongly shifted upfield, ~0.0145 ppm/K, which is due to weakening of the hydrogen-bonding network of the confined EAN. Exposure to the magnetic field leads to restitution of the hydrogen-bonding (H-bonding network). The temperature dependences of diffusion coefficients follow the order D(I) > D(IB) > D(IMF) and can be described by a Vogel-Fulcher-Tammann approach with variation of the pre-exponential factor, which is determined by the strength of the H-bonding network. Confinement of EAN between plates (IB â I) is an endothermic process, while processes occurring in a magnetic field, I â IMF and IMF â I, are exothermic and endothermic, respectively.
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Líquidos Iónicos/química , Espectroscopía de Protones por Resonancia Magnética , Compuestos de Amonio Cuaternario/química , Temperatura , Difusión , Enlace de HidrógenoRESUMEN
Ion transport behaviour of halogen-free hybrid electrolytes for lithium-ion batteries based on phosphonium bis(salicylato)borate [P4,4,4,8][BScB] ionic liquid mixed with diethylene glycol dibutyl ether (DEGDBE) is investigated. The Li[BScB] salt is dissolved at different concentrations in the range from 0.15 mol kg-1 to 1.0 mol kg-1 in a mixture of [P4,4,4,8][BScB] and DEGDBE in 1:5 molar ratio. The ion transport properties of the resulting electrolytes are investigated using viscosity, electrical impedance spectroscopy and pulsed-Field Gradient (PFG) NMR. The apparent transfer numbers of ions are calculated from the diffusion coefficients measured by using PFG NMR. PFG NMR data suggested ion association upon addition of Li salt to the [P4,4,4,8][BScB] in DEGDBE solution. This is further confirmed by liquid state 7Li and 11B NMR, and FTIR spectroscopic techniques, which suggest strong interactions between the lithium cation and oxygen atoms of the [BScB]- anion in the hybrid electrolytes.
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Diffusion of EAN confined between polar glass plates separated by a few micrometers is higher by a factor of ca. 2 as compared to bulk values. Formation of a new phase, different to the bulk, was suggested.
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This study was focused on the investigation of ion dynamics in halogen-free, hydrophobic, and hydrolytically stable phosphonium bis(salicylato)borate [P4,4,4,8][BScB] ionic liquid electrolytes for lithium-ion batteries. The structure and purity of the synthesized ionic liquid and lithium bis(salicylato)borate Li[BScB] salt were characterized using 1H, 13C, 31P, and 11B NMR spectroscopy. The Li[BScB] salt was mixed with an ionic liquid at the concentrations ranging from 2.5 mol% to 20 mol%. The physicochemical properties of the resulting electrolytes were characterized using thermal analysis (TGA and DSC), electrical impedance spectroscopy, and pulsed-field gradient (PFG) NMR and ATR-FTIR spectroscopy. The apparent transfer numbers of the individual ions were calculated from the diffusion coefficients of the cation and anion as determined via the PFG NMR spectroscopy. NMR and ATR-FTIR spectroscopic techniques revealed dynamic interactions between the lithium cation and bis(salicylato)borate anion in the electrolytes. The ion-ion interactions were found to increase with the increasing concentration of the Li[BScB] salt, which resulted in ionic clustering at the concentrations higher than 15 mol% of Li salt in the ionic liquid.
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Ionic liquid (1-ethyl-3-methylimidazolium acetate, [C2C1im][AcO])-copper(ii) diacetate monohydrate-water-air (O2) systems have been investigated by (13)C NMR, EPR, spectrophotometry, HPLC, and synthetic chemistry methods at different temperatures. The C-H bond activation of [C2C1im](+) with the formation of the unusual dication 1,1'-diethyl-3,3'-dimethyl-2,2'-biimidazolium ([(C2C1im)2](2+)) at 50 °C and 1-ethyl-3-methyl-1H-imidazol-2(3H)-one (C2C1imO) at 50-85 °C was revealed. Two new complexes with the above compounds, [(C2C1im)2][Cu(AcO)4] and Cu2(AcO)4(C2C1imO)2, were isolated from the systems and characterized by X-ray structural analysis. Catalytic cycles with the participation of copper(ii) acetate and dioxygen and the production of [(C2C1im)2](2+) and C2C1imO have been proposed. The catalysis presumably includes the formation of the Cu(II)(O2)Cu(II) active centre with µ-η(2):η(2)-peroxide bridging in analogy with tyrosinase and catechol oxidase activity.
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Acetatos/química , Aire , Cobre/química , Imidazoles/química , Oxígeno/química , Agua/química , Carbono/química , Hidrógeno/química , Modelos Moleculares , Conformación Molecular , Oxidación-Reducción , TemperaturaRESUMEN
The article represents the results of research in self-organization of new lanthanide systems in water-decanol medium. The systems are based on N,N-dimethyldodecylamine oxide, a zwitterionic surfactant. The study covers the complex formation of lanthanide ions with C12DMAO molecules and the influence of Ln(III) ions and medium composition on surfactant association in diluted solutions. The analysis of adsorption isotherms was carried out on the basis of the combination of Gibbs and Langmuir adsorption equations. The results were used to determine physicochemical properties and parameters of a monomolecular adsorption layer. The research objects were various lanthanide ions with identical coordination centers. A number of spectroscopic methods (UV, NMR self-diffusion, EPR, dynamic light scattering (DLS), and fluorescent analysis) were involved in the research for comparative estimations of molecular dynamics, critical micellization concentration, geometry, sizes, and aggregation numbers of micellar aggregates. Micelle structure simulation revealed good agreement between experimental data and quantum chemical calculations.
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The lipoxygenase pathway in sunflower roots was studied in vitro. A preliminary incubation of linoleic acid with 15 000 g supernatant of homogenate of sunflower roots (1.5-6 days after germination) revealed the predominant activity of 13-lipoxygenase. The exogenously added linoleic acid 13-hydroperoxide is further utilized through two competing pathways. One of them is directed towards formation of the ketodiene (9Z,11E)-13-oxooctadeca-9,11-dienoic acid. The second pathway, which is controlled by allene oxide synthase, leads to the formation of an alpha-ketol and a novel cyclopentenone, rac-cis-12-oxo-10-phytoenoic acid (12-oxo-PEA) via a short-lived allene oxide. Unexpectedly, the cyclopentenone 12-oxo-PEA is the predominant allene oxide synthase product. Identification of cis-12-oxo-PEA was confirmed by its UV, mass, (1)H NMR and 2D-COSY spectral data. The highest yield of 12-oxo-PEA is observed in very young roots (1.5-2 days after germination). The results of methanol-trapping experiments demonstrate that both 12-oxo-PEA and alpha-ketol are formed through the unstable allene oxide intermediate, (9Z)-12,13-epoxyoctadeca-9,11-dienoic acid, which is the primary product of allene oxide synthase. Since 12-oxo-PEA is a jasmonate congener, its biosynthesis in plants might be of physiological importance.