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The purpose of this research is to design nanocomposite materials for biomedical applications. New conjugates of PEG derivatives of RGD peptides and magnetic nanoparticles, based on Fe3O4 (MNPs) with silica coating covalently labelled with fluorescent dye Cyanine5, were obtained. It was shown that a higher loading level of RGD peptides occurred in the case of MNPs with SiO2/aminopropylsilane coating, synthesised using N-(phosphonomethyl)iminodiacetic acid (PMIDA) as a surfactant. To confirm the structure and chemical purity of the new RGD-PEG conjugate, a number of methods were used, including 1H NMR, HRMS, and RP-HPLC. The characterisation of MNPs was carried out using the following physical methods: TEM, FTIR, EDX, CHN analysis, DLS, fluorescence spectrometry, vibration magnetometry, and relaxometry. Samples obtained from PMIDA-stabilised MNPs contained a greater amount of the peptide and possessed better hydrodynamic characteristics than samples obtained from non-stabilised MNPs. A comparative study of the MNP cytotoxicity was carried out towards 4T1 and MDA-MB231 cell lines (MTT test), and the possibility of cell labelling was assessed. The cellular uptake was more efficient for nanoconjugates obtained without PMIDA. The data obtained can be used for the design of materials for cell labelling and visualisation. [ABSTRACT FROM AUTHOR]

A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids–MPTA and peptides–MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure. [ABSTRACT FROM AUTHOR]

A series of new 2-(indol-3-yl)-6-(hetero)aryl substituted pyridines, 2-(indol-3-yl)-5-phenyl-substituted 2,2′-bipyridine and 5-aryl-6-(pyrrol-2-yl) substituted 2,2′-bipyridines were synthesized as push–pull fluorophores/probes by using a sequence of nucleophilic substitution reaction of hydrogen (SNH) and inverse-demand Diels–Alder reaction. For the obtained compounds, photophysical properties were studied. All the compounds displayed ICT-activity with a large Stokes shift (up to 197 nm) and PLQY up to 0.28. Due to dual emission in polar solvents, one specific probe was able to respond to the action of the local pH changes in the microenvironment and exhibit AIE-activity. The fluorescence titration data at different pH were analyzed to estimate a pKa value of 4.50 for that specific probe. The AIE behavior was further confirmed by means of time-resolved fluorescence lifetime measurements as well as UV-vis spectroscopic studies. The correlation of the influence of the nature of substituents on the degree of ICT state was established based on the analysis of charge transfer (CT) indices and the calculated interfragment charge transfer (IFCT) values. Finally, the fluorophores reported in this study were successfully applied for cellular imaging. [ABSTRACT FROM AUTHOR]

In this paper, the electron and magnetic state of iron placed either on the surface or in the core of TiO2 nanoparticles were investigated using magnetometric methods, electron paramagnetic resonance (EPR) and Mössbauer spectroscopy. It was demonstrated that the EPR spectra of TiO2 samples with iron atoms localized both on the surface and in the core of specific features depending on the composition and size of the nanoparticles. Theoretical calculations using the density functional theory (DFT) method demonstrated that the localization of Fe atoms on the surface is characterized by a considerably larger set of atomic configurations as compared to that in the core of TiO2 nanoparticles. Mössbauer spectra of the samples doped with Fe atoms both on the surface and in the core can be described quite satisfactorily using two and three doublets with different quadrupole splitting, respectively. This probably demonstrates that the Fe atoms on particle surface and in the bulk are in different unlike local surroundings. All iron ions, both on the surface and in the core, were found to be in the Fe3+ high-spin state. [ABSTRACT FROM AUTHOR]

Novel magnetic nanocomposite materials based on Fe3O4 nanoparticles coated with iron and silica glycerolates (MNP@Fe(III)Glyc and MNP@Fe(III)/SiGlyc) were obtained. The synthesized nanocomposites were characterized using TEM, XRD, TGA, VMS, Mössbauer and IR spectroscopy. The amount of iron and silica glycerolates in the nanocomposites was calculated from the Mössbauer spectroscopy, ICP AES and C,H-elemental analysis. Thus, it has been shown that the distribution of Fe in the shell and core for MNP@Fe(III)Glyc and MNP@Fe(III)/SiGlyc is 27:73 and 32:68, respectively. The synthesized nanocomposites had high specific magnetization values and a high magnetic response to the alternating magnetic field. The hydrolysis of shells based on Fe(III)Glyc and Fe(III)/SiGlyc in aqueous media has been studied. It has been demonstrated that, while the iron glycerolates shell of MNP@Fe(III)Glyc is resistant to hydrolysis, the silica glycerolates shell of MNP@Fe(III)/SiGlyc is rather labile and hydrolyzed by 76.4% in 24 h at 25 °C. The synthesized materials did not show cytotoxicity in in vitro experiments (MTT-assay). The data obtained can be used in the design of materials for controlled-release drug delivery. [ABSTRACT FROM AUTHOR]

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking. [ABSTRACT FROM AUTHOR]

Novel nanocomposite materials based on Fe3O4 magnetic nanoparticles (MNPs) coated with silica and covalently modified by [(3-triethoxysilyl)propyl]succinic acid–polyethylene glycol (PEG 3000) conjugate, which provides a high level of doxorubicin (Dox) loading, were obtained. The efficiency of Dox desorption from the surface of nanomaterials under the action of an alternating magnetic field (AMF) in acidic and neutral media was evaluated. Their high cytotoxicity against tumor cells, as well as the drug release upon application of AMF, which leads to an increase in the cytotoxic effect, was demonstrated. [ABSTRACT FROM AUTHOR]