A supramolecular catalyst based on sodium alginate and viologen calix[4]resorcinol for the room temperature hydrolysis of paraoxon.

Properties of paraoxon, such as poor water solubility, low rate of natural decomposition, ability to accumulate in soil and wastewater, lead to the fact that paraoxon is found in various agricultural products and textiles. In this regard, the search for effective ways of paraoxon degradation becomes an extremely urgent problem, which can be solved by creating catalysts by mimicking paraxonase. In this work, a complex of physicochemical methods was used to study the supramolecular interactions of sodium alginate, which has a calcium-binding ability similar to paraxonase, with viologen calix[4]resorcinol and to reveal the nature of the intermolecular interactions between them resulting in the spontaneous formation of nanoparticles. Before proceeding to the investigation of the binding ability of obtained nanoparticles to paraoxon, the encapsulating effect of nanoparticles on a number of model substrates of different solubility (doxorubicin hydrochloride, quercetin and oleic acid) was studied. The kinetics of paraoxon hydrolysis reaction using these nanoparticles was studied at room temperature in an aqueous medium by spectrophotometric method. The rate of this reaction increases with increasing concentration of stable nanoparticles having hydrophobic domains that ensure paraoxon immobilization. The results obtained allow considering the supramolecular polysaccharide/calixarene system as an effective biomimetic catalyst.

Green-step assembly of the supramolecular amphiphile constructed by sodium carboxymethyl cellulose and calixarene for facile loading of hydrophobic food bioactive compounds.

The use of biologically active compounds is often limited due to their poor aqueous solubility, which generally reduces their bioavailability and useful efficacy. In this regard, a wide search is currently underway for colloidal systems capable of encapsulating these compounds. In the creation of colloidal systems, long-chain molecules of surfactants and polymers are mainly used, which in an individual state do not always aggregate into homogeneous and stable nanoparticles. In the present work, cavity-bearing calixarene was used for the first time to order polymeric molecules of sodium carboxymethyl cellulose. A set of physicochemical methods demonstrated the spontaneous formation of spherical nanoparticles by non-covalent self-assembly contributed by macrocycle and polymer, and formed nanoparticles were able to encapsulate hydrophobic quercetin and oleic acid. The preparation of nanoparticles by supramolecular self-assembly without use of organic solvents, temperature and ultrasound effects can be an effective strategy for creating water-soluble forms of lipophilic bioactive compounds.

Emergence of Nanoscale Drug Carriers through Supramolecular Self-Assembly of RNA with Calixarene.

Supramolecular self-assembly is a powerful tool for the development of polymolecular assemblies that can form the basis of useful nanomaterials. Given the increasing popularity of RNA therapy, the extension of this concept of self-assembly to RNA is limited. Herein, a simple method for the creation of nanosized particles through the supramolecular self-assembly of RNA with a three-dimensional macrocycle from the calixarene family was reported for the first time. This self-assembly into nanoparticles was realized using cooperative supramolecular interactions under mild conditions. The obtained nanoparticles are able to bind various hydrophobic (quercetin, oleic acid) and hydrophilic (doxorubicin) drugs, as a result of which their cytotoxic properties are enhanced. This work demonstrates that intermolecular interactions between flexible RNA and rigid calixarene is a promising route to bottom-up assembly of novel supramolecular soft matter, expanding the design possibilities of nanoscale drug carriers.

Supramolecular Self-Assembly of Porphyrin and Metallosurfactant as a Drug Nanocontainer Design.

The combined method of treating malignant neoplasms using photodynamic therapy and chemotherapy is undoubtedly a promising and highly effective treatment method. The development and establishment of photodynamic cancer therapy is closely related to the creation of sensitizers based on porphyrins. The present study is devoted to the investigation of the spectroscopic, aggregation, and solubilization properties of the supramolecular system based on 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TSPP) and lanthanum-containing surfactant (LaSurf) in an aqueous medium. The latter is a complex of lanthanum nitrate and two cationic amphiphilic molecules of 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide. The mixed TSPP-LaSurf complexes can spontaneously assemble into various nanostructures capable of binding the anticancer drug cisplatin. Morphological behavior, stability, and ability to drug binding of nanostructures can be tailored by varying the molar ratio and the concentration of components. The guest binding is shown to be additional factor controlling structural rearrangements and properties of the supramolecular TSPP-LaSurf complexes.

Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential.

Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide units, and calix[4]resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle-metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle-metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle-metallosurfactant system for the design of therapeutic cisplatin compositions.

Design of N-Methyl-d-Glucamine-Based Resorcin[4]arene Nanoparticles for Enhanced Apoptosis Effects.

The addition of specific chemical groups in a macrocycle structure influences its functional properties and, consequently, can provide new possibilities, among which are aggregation properties, water solubility, biocompatibility, stimuli response, biological activity, etc. Herein, we report synthesis of new resorcin[4]arene with N-methyl-d-glucamine groups on the upper rim and n-decyl chains on the lower rim, an investigation of its self-assembly behavior in aqueous media, and its use as a building block for the formation of drug nanocontainer. N-methyl-d-glucamine fragments in the resorcin[4]arene structure promote higher stability in solutions, simplification of self-aggregation, and increased biological activity. Antimicrobial and hemolytic activity assessment revealed that this resorcin[4]arene obtained is nontoxic. The study of cell penetration was carried out with both free and encapsulated doxorubicin (DOX). Surprisingly, DOX-loaded macrocycle aggregates are more efficient in causing apoptosis in human cancer cell line. Conceivably, this knowledge will help in the rational design of DOX combination for novel drug-administration strategies in cancer treatment.

N-Methyl-d-glucamine-Calix[4]resorcinarene Conjugates: Self-Assembly and Biological Properties.

Deep insight of the toxicity of supramolecular systems based on macrocycles is of fundamental interest because of their importance in biomedical applications. What seems to be most interesting in this perspective is the development of the macrocyclic compounds with biocompatible fragments. Here, calix[4]resorcinarene derivatives containing N-methyl- d-glucamine moieties at the upper rim and different chemical groups at the lower rim were synthesized and investigated. These macrocycles showed a tendency to self-aggregate in aqueous solution, and their self-assembly abilities depend on the structure of the lower rim. The in vitro cytotoxic and antimicrobial activity of the calix[4]resorcinarenes revealed the relationship of biological properties with the ability to aggregate. Compared to macrocycles with methyl groups on the lower rim, calix[4]resorcinarenes with sulfonate groups appear to possess very similar antibacterial properties, but over six times less hemolytic activity. In some ways, this is the first example that reveals the dependence of the observed hemolytic and antibacterial activity on the lipophilicity of the calix[4]arene structure.

Self-assembling and biological properties of single-chain dicationic pyridinium-based surfactants.

In this work, the dicationic surfactants containing viologen and vinylbipyridinium moieties and hexadecyl chains were synthesized, and their aggregation behavior in water solutions was investigated by surface tension, conductivity measurements, hydrophobic probe solubilization, dynamic light scattering and electrophoretic measurements. Effect of UV-light on cis-trans isomerism of vinylbipyridinium derivative was determined. Antimicrobial activity and the influence of these surfactants on cell viability depended on the concentration and type of surfactant used. The results obtained established the structure-property (physicochemical properties and biological activity) relationship of the surfactant molecule namely the primary role of pyridinium head group structure.