Phase Transition Thermodynamics of 1,3,5-Tris-(α-naphthyl)benzene: Theory and Experiment.

1,3,5-Tris-(α-naphthyl)benzene is an organic non-electrolyte with notable stability of an amorphous phase. Its glassy and supercooled liquid states were previously studied by spectroscopic and calorimetric methods. Despite the continuing interest in its amorphous state and, particularly, vapor-deposited glasses, the thermodynamic parameters of the vaporization of 1,3,5-tris-(α-naphthyl)benzene have not been obtained yet. Likewise, the reliable evaluation of the thermodynamic parameters of fusion below the melting point, required to establish the thermodynamic state of its glass, is still an unsolved problem. In this work, the heat capacities of crystalline and liquid phases, the temperature dependence of the saturated vapor pressures, fusion and vaporization enthalpies were determined using differential and fast scanning calorimetry and were verified using the estimates based on solution calorimetry. The structural features of 1,3,5-tris-(α-naphthyl)benzene are discussed based on the computations performed and the data on the molecular refractivity. The consistency between the values obtained by independent techniques was demonstrated.

New ionic liquids based on 5-fluorouracil: Tuning of BSA binding and cytotoxicity.

In this work, we describe the synthesis, interactions with bovine serum albumin, and cytotoxicity of new ionic liquids based on 5-fluorouracil (API-ILs) with different cations (imidazolium, choline, isoquinolinium, guanidinium). The secondary and tertiary structure of BSA in solutions with different concentrations of API-ILs was monitored by the circular dichroism (CD) technique. The addition of API-ILs does not lead to structural changes in BSA. A quenching of fluorescence spectra intensity of BSA in presence of all API-ILs was observed, allowing the quantification of binding between API-ILs and BSA. The preferred localization of both ions in API-ILs differs significantly depending on the structure of the cation according to molecular docking. The aggregation of BSA in presence of API-ILs was analyzed by the dynamic light scattering (DLS) method, revealing a moderate increase in particle size. Cytotoxicity and selectivity of API-ILs on cancer and normal cell lines were estimated, showing a clear modification of the pharmaceutic activity of ionic liquid compared to 5-fluorouracil.

Extent of N-Terminus Folding of Semenogelin 1 Cleavage Product Determines Tendency to Amyloid Formation.

It is known that four peptide fragments of predominant protein in human semen Semenogelin 1 (SEM1) (SEM1(86-107), SEM1(68-107), SEM1(49-107) and SEM1(45-107)) are involved in fertilization and amyloid formation processes. In this work, the structure and dynamic behavior of SEM1(45-107) and SEM1(49-107) peptides and their N-domains were described. According to ThT fluorescence spectroscopy data, it was shown that the amyloid formation of SEM1(45-107) starts immediately after purification, which is not observed for SEM1(49-107). Seeing that the peptide amino acid sequence of SEM1(45-107) differs from SEM1(49-107) only by the presence of four additional amino acid residues in the N domain, these domains of both peptides were obtained via solid-phase synthesis and the difference in their dynamics and structure was investigated. SEM1(45-67) and SEM1(49-67) showed no principal difference in dynamic behavior in water solution. Furthermore, we obtained mostly disordered structures of SEM1(45-67) and SEM1(49-67). However, SEM1(45-67) contains a helix (E58-K60) and helix-like (S49-Q51) fragments. These helical fragments may rearrange into ß-strands during amyloid formation process. Thus, the difference in full-length peptides' (SEM1(45-107) and SEM1(49-107)) amyloid-forming behavior may be explained by the presence of a structured helix at the SEM1(45-107) N-terminus, which contributes to an increased rate of amyloid formation.

Calix[4]Resorcinarene Carboxybetaines and Carboxybetaine Esters: Synthesis, Investigation of In Vitro Toxicity, Anti-Platelet Effects, Anticoagulant Activity, and BSA Binding Affinities.

As a result of bright complexation properties, easy functionalization and the ability to self-organize in an aqueous solution, amphiphilic supramolecular macrocycles are being actively studied for their application in nanomedicine (drug delivery systems, therapeutic and theranostic agents, and others). In this regard, it is important to study their potential toxic effects. Here, the synthesis of amphiphilic calix[4]resorcinarene carboxybetaines and their esters and the study of a number of their microbiological properties are presented: cytotoxic effect on normal and tumor cells and effect on cellular and non-cellular components of blood (hemotoxicity, anti-platelet effect, and anticoagulant activity). Additionally, the interaction of macrocycles with bovine serum albumin as a model plasma protein is estimated by various methods (fluorescence spectroscopy, synchronous fluorescence spectroscopy, circular dichroic spectroscopy, and dynamic light scattering). The results demonstrate the low toxicity of the macrocycles, their anti-platelet effects at the level of acetylsalicylic acid, and weak anticoagulant activity. The study of BSA-macrocycle interactions demonstrates the dependence on macrocycle hydrophilic/hydrophobic group structure; in the case of carboxybetaines, the formation of complexes prevents self-aggregation of BSA molecules in solution. The present study demonstrates new data on potential drug delivery nanosystems based on amphiphilic calix[4]resorcinarenes for their cytotoxicity and effects on blood components.

Water-soluble pillar[5]arene sulfo-derivatives self-assemble into biocompatible nanosystems to stabilize therapeutic proteins.

Pillar[5]arenes containing sulfonate fragments have been shown to form supramolecular complexes with therapeutic proteins to facilitate targeted transport with an increased duration of action and enhanced bioavailability. Regioselective synthesis was used to obtain a water-soluble pillar[5]arene containing the fluorescent label FITC and nine sulfoethoxy fragments. The pillar[5]arene formed complexes with the therapeutic proteins binase, bleomycin, and lysozyme in a 1:2 ratio as demonstrated by UV-vis and fluorescence spectroscopy. The formation of stable spherical nanosized macrocycle/binase complexes with an average particle size of 200 nm was established by dynamic light scattering and transmission electron microscopy. Flow cytometry demonstrated the ability of macrocycle/binase complexes to penetrate into tumor cells where they exhibited significant cytotoxicity towards A549 cells at 10-5-10-6 M while maintaining the enzymatic activity of binase.

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.