Polyaromatic Hydrocarbon (PAH)-Based Aza-POPOPs: Synthesis, Photophysical Studies, and Nitroanalyte Sensing Abilities.

1,4-Bis(5-phenyl-2-oxazolyl)benzene (POPOP) is a common scintillation fluorescent laser dye. In this manuscript, the synthesis of 2-Ar-5-(4-(4-Ar'-1H-1,2,3-triazol-1-yl)phenyl)-1,3,4-oxadiazoles (Ar, Ar' = Ph, naphtalenyl-2, pyrenyl-1, triphenilenyl-2), as PAH-based aza-analogues of POPOP, by means of Cu-catalyzed click reaction between 2-(4-azidophenyl)-5-Ar-1,3,4-oxadiazole and terminal ethynyl-substituted PAHs is reported. An investigation of the photophysical properties of the obtained products was carried out, and their sensory response to nitroanalytes was evaluated. In the case of pyrenyl-1-substituted aza-POPOP, dramatic fluorescence quenching by nitroanalytes was observed.

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.

Nanoconjugates of a calixresorcinarene derivative with methoxy poly(ethylene glycol) fragments for drug encapsulation.

In order to obtain a non-toxic amphiphilic calixresorcinarene capable to form nanoconjugates for drug encapsulation, tetraundecylcalixresorcinarene functionalized by methoxy poly(ethylene glycol) chains has been synthesized. The macrocycle obtained is characterized by low hemotoxicity. In aqueous solution it forms nanoassociates that are able to encapsulate organic substrates of different hydrophobicity, including drugs (doxorubicin, naproxen, ibuprofen, quercetin). The micelles of the macrocycle slowed down the release of the hydrophilic substrates in vitro. In physiological sodium chloride solution and phosphate-buffered saline, the micelles of the macrocycle acquire thermoresponsive properties and exhibit a temperature-controlled release of doxorubicin in vitro. The combination of the low toxicity and the encapsulation properties of the obtained calixresorcinarene-mPEG conjugate shows promising potential for the use as a supramolecular drug-delivery system.

Crystal violet dye in complexes with amphiphilic anionic calix[4]resorcinarenes: binding by aggregates and individual molecules.

Here, we report on a systematic study of six calix[4]resorcinarene macrocycles bearing eight carboxylic groups on the upper rim and four different lower rim substituents that are either aliphatic (2, 4, and 5) or alkylaromatic (1, 3, and 6). The macrocycles were studied in their individual aqueous solutions and in the presence of triphenylmethane dye crystal violet. It was found that binding of crystal violet with aggregated macrocycles shields it from the bulk of solution, preventing its discoloration under basic conditions and electrochemical reduction on the glassy carbon electrode. Most efficient shielding, reducing the rate of discoloration more than 173 times, as compared to solution with no macrocycle, was achieved with 6 forming aggregates of average 72 molecules in 0.1 mM solutions.

Guest controlled aggregation of amphiphilic sulfonatomethylated calix[4]resorcinarenes in aqueous solutions.

Supramolecular nanoaggregates formed through the association of amphiphilic sulfonatomethylated calix[4]resorcinarenes with different substituents on the lower rim (methyl, pentyl, heptyl) and number of aromatic, aliphatic, and cationic guests differing in their shapes and sizes were investigated in aqueous solution by various NMR techniques ((1)H, 2D NOESY, FT-PGSE). It was shown that slight variations of the alkyl chain length on the lower rim of calixresorcinarenes dramatically change their aggregation behavior. Unlike the other calixresorcinarenes studied, the "head-to-tail" packing mode is observed for calixresorcinarene with pentyl moieties on the lower rim, which is unusual for amphiphilic calixarene aggregates. This calixresorcinarene demonstrates the stronger binding capacity toward the guest molecules due to their encapsulation into the capsule-like aggregate subunits. The guest-host complexation modifies the properties of both components, with the size of the resulted colloid particles being controlled by the guest nature.

Investigation of tetramethylenesulfonated calix[4]resorcinarene interactions with azo dyes in aqueous solution.

The interaction of a macrocycle's aggregates with a guest molecule has special interest due to the double role, both of macrocycle cavity and self-associates, in the binding of the guests. Here, we report on the interactions of nonaggregated methyl-substituted (SCA1) and aggregated penthyl-substituted (SCA2) tetramethylenesulfonated calix[4]resorcinarenes with pH indicators methyl yellow (MY) and methyl orange (MO) in aqueous solutions. It was found that the pH of aqueous solutions of SCA1 and SCA2 depends on their concentration; besides, variation of the concentration of SCA1 and SCA2 results in a shift of the absorption maxima and of pH-sensitive azo dyes. Association of the marocycles with azo dyes was demonstrated to follow a proton-transfer mechanism accompanied by protonation of the dyes; it was found that excess of the macrocycle in solution with the universal buffer background shifts the pK(a) values and stabilizes the protonated form of the dyes. Consideration of interactions of small dye molecules with large molecular associates, containing both individual and multimolecule binding sites, gives a closer approximation of synthetic biomimetics to their natural prototypes.