Towards controlling the morphology of cobalt loaded nanocomposites in polyol process with polyethylene glycol

The polyol process is one of the simple, efficient and productive methods for the synthesis of metal loaded polymer composites. Functional properties of metal-polymer nanocomposites are determined by chemical composition, size and morphology of their particles. Finding effective ways to control the nanoparticle's properties during the polyol process is a crucial task. The effect of molar ratio Mn+/OHPEG on the formation of cobalt loaded metal-polymer nanocomposites during a one-pot two-component polyol process by polyethylene glycol with Mr = 4000 g·mol–1 (PEG) was studied. The PEG-based polyol process and the formation of cobalt nanophase were studied at molar ratios νCo2+/νOH(PEG) = 1:1, 1:10, 1:100 and 1:500 using UV-Vis, diffuse reflectance IR and ATR FT-IR spectroscopy, nanoparticle tracking analysis (NTA), dynamic light scattering (DLS). It was found that PEG can act as a reducing agent and stabilizing matrix for the cobalt nanophase at a ratio higher than Mn+/OHPEG= 1:10. The composition and morphology of Co/PEG nanocomposites were determined by XRD and TEM methods. Two types of spheroid particles with average diameters of 88±55 nm / 8±4 nm and 12±3 nm / 3±1 nm, respectively, represent Co/PEG nanocomposites 1:500 and 1:100. Scaly structures with a diameter of 15±5 nm are formed at a molar ratio of νCo2+/νOH(PEG) = 1:10. An increase in the Co2+ content in the PEG-based polyol process leads to the immobilized cobalt nanophase Co3O4 (1:500), Co0/CoO (1:100), CoO (1:10) in PEG. Co/PEG nanocomposites are hemocompatible. The HC50value depends on the composition and morphology of the nanoparticles

PAMAM-calix-dendrimers: Synthesis and Thiacalixarene Conformation Effect on DNA Binding

A convenient method for the synthesis of the first generation PAMAM dendrimers based on the thiacalix[4]arene has been developed for the first time. Three new PAMAM-calix-dendrimers with the macrocyclic core in cone, partial cone, and 1,3-alternate conformations were obtained with high yields. The interaction of the obtained compounds with salmon sperm DNA resulted in the formation of the associates of the size up to 200 nm, as shown by the UV-Vis spectroscopy, DLS, and TEM. It was demonstrated by the CD method that the structure of the DNA did not undergo significant changes upon binding. The PAMAM-calix-dendrimer based on the macrocycle in cone conformation stabilized DNA and prevented its degradation

Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding

The synthesis of new phenothiazine derivatives, analogs of Methylene Blue, is of particular interest in the design of new drugs, as well as in the development of a new generation of agents for photodynamic therapy. In this study, two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino)phenothiazin-5-ium chloride dihydrochloride (PTZ1) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (PTZ2), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds PTZ1 and PTZ2 with salmon sperm DNA is investigated. It is shown by UV-Vis spectroscopy and DFT calculations that substituents in arylamine fragments play a crucial role in dimer formation and interaction with DNA. In the case of PTZ1, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of PTZ2, sulfanilic acid fragments prevent any dimer formation and DNA binding due to electrostatic repulsion. DNA interaction mechanisms are studied and confirmed by UV-vis and fluorescence spectroscopy in comparison with Methylene Blue. The obtained results open significant opportunities for the development of new drugs and photodynamic agents

PAMAM-Calix-Dendrimers: Second Generation Synthesis, Fluorescent Properties and Catecholamines Binding

A convenient method for the synthesis of the second generation of PAMAM dendrimers based on a p-tert-butylthiacalix[4]arene core in cone, partial cone and 1,3-alternate conformations was developed. Unusual fluorescence of the obtained PAMAM-calix-dendrimers has been found and explained. The binding ability of the synthesized dendrimers toward catecholamines (dopamine, L-adrenaline and L-noradrenaline) was shown by UV-Vis, fluorescence, 1D and 2D NMR spectroscopy and the binding constants (logKa 3.85–4.74) calculated. As was shown, the PAMAM-calix-dendrimers bind catecholamines by the internal cavities. All the studied hormones were most efficiently bound by the dendrimers bearing a macrocyclic core in 1,3-alternate conformation. The size of the formed supramolecular systems of dendrimer/catecholamine was established by the DLS method. A decrease in hemolytic activity of the PAMAM-calix-dendrimers with an increase in the generation number of a dendrimer was shown for the dendrimers with a core in 1,3-alternate conformation. The prospects for the use of the synthesized dendrimers with the macrocyclic core as drug delivery agents were discussed

Albumin/Thiacalix[4]arene Nanoparticles as Potential Therapeutic Systems: Role of the Macrocycle for Stabilization of Monomeric Protein and Self-Assembly with Ciprofloxacin

The therapeutic application of serum albumin is determined by the relative content of the monomeric form compared to dimers, tetramers, hexamers, etc. In this paper, we propose and develop an approach to synthesize the cone stereoisomer of p-tert-butylthiacalix[4]arene with sulfobetaine fragments stabilization of monomeric bovine serum albumin and preventing aggregation. Spectral methods (UV-vis, CD, fluorescent spectroscopy, and dynamic light scattering) established the influence of the synthesized compounds on the content of monomeric and aggregated forms of BSA even without the formation of stable thiacalixarene/protein associates. The effect of thiacalixarenes on the efficiency of protein binding with the antibiotic ciprofloxacin was shown by fluorescence spectroscopy. The binding constant increases in the presence of the macrocycles, likely due to the stabilization of monomeric forms of BSA. Our study clearly shows the potential of this macrocycle design as a platform for the development of the fundamentally new approaches for preventing aggregation

Nanostructured Polyelectrolyte Complexes Based on Water-Soluble Thiacalix[4]Arene and Pillar[5]Arene: Self-Assembly in Micelleplexes and Polyplexes at Packaging DNA

Controlling the self-assembly of polyfunctional compounds in interpolyelectrolyte aggregates is an extremely challenging task. The use of macrocyclic compounds offers new opportunities in design of a new generation of mixed nanoparticles. This approach allows creating aggregates with multivalent molecular recognition, improved binding efficiency and selectivity. In this paper, we reported a straightforward approach to the synthesis of interpolyelectrolytes by co-assembling of the thiacalix[4]arene with four negatively charged functional groups on the one side of macrocycle, and pillar[5]arene with 10 ammonium groups located on both sides. Nanostructured polyelectrolyte complexes show effective packaging of high-molecular DNA from calf thymus. The interaction of co-interpolyelectrolytes with the DNA is completely different from the interaction of the pillar[5]arene with the DNA. Two different complexes with DNA, i.e., micelleplex- and polyplex-type, were formed. The DNA in both cases preserved its secondary structure in native B form without distorting helicity. The presented approach provides important advantage for the design of effective biomolecular gene delivery systems

Self-assembly of chiral fluorescent nanoparticles based on water-soluble L-tryptophan derivatives of p-tert-butylthiacalix[4]arene

New water-soluble tetra-substituted derivatives of p-tert-butylthiacalix[4]arene containing fragments of L-tryptophan in cone and 1,3-alternate conformations were obtained. It was shown that the resulting compounds form stable, positively charged aggregates of 86–134 nm in diameter in water at a concentration of 1 × 10−4 M as confirmed by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. It was established that these aggregates are fluorescently active and chiral. A distinctive feature of the compounds is the pronounced dependence of their spectral (emission and chiroptical) properties on the polarity of the solvent and the length of the linker between the macrocyclic and fluorophore parts of the molecule

Towards Universal Stimuli-Responsive Drug Delivery Systems: Pillar[5]arenes Synthesis and Self-Assembly into Nanocontainers with Tetrazole Polymers

In this work, we have proposed a novel universal stimulus-sensitive nanosized polymer system based on decasubstituted macrocyclic structures—pillar[5]arenes and tetrazole-containing polymers. Decasubstituted pillar[5]arenes containing a large, good leaving tosylate, and phthalimide groups were first synthesized and characterized. Pillar[5]arenes containing primary and tertiary amino groups, capable of interacting with tetrazole-containing polymers, were obtained with high yield by removing the tosylate and phthalimide protection. According to the fluorescence spectroscopy data, a dramatic fluorescence enhancement in the pillar[5]arene/fluorescein/polymer system was observed with decreasing pH from neutral (pH = 7) to acidic (pH = 5). This indicates the destruction of associates and the release of the dye at a pH close to 5. The presented results open a broad range of opportunities for the development of new universal stimulus-sensitive drug delivery systems containing macrocycles and nontoxic tetrazole-based polymers