ABSTRACT
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.
Subject(s)
Apoptosis/drug effects , Calixarenes/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Antibiotics, Antineoplastic/administration & dosage , Calixarenes/chemical synthesis , Cell Line, Tumor , Doxorubicin/administration & dosage , Hepatocytes/drug effects , Humans , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , SolubilityABSTRACT
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.
Subject(s)
Calixarenes/chemistry , Calixarenes/pharmacology , Phenylalanine/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Calixarenes/chemical synthesis , Cell Death/drug effects , Diffusion , Electric Conductivity , Humans , Macrocyclic Compounds/chemistry , Particle Size , Phenylalanine/chemical synthesis , Phenylalanine/chemistry , Phenylalanine/pharmacology , Static Electricity , Surface TensionABSTRACT
A nanocarrier (p(6SRA-5B)) for glucose-controlled insulin delivery consists of sulfonated resorcinarenes (SRA) that are assembled into a spherical shell and are attached to each other with phenylboronate linkers. p(6SRA-5B) is stable in water and blood plasma at normal glucose concentrations. At high glucose levels (>5â mM), p(6SRA-5B) dissociates into SRA and phenylboronates through competitive interaction with excess glucose. Insulin was successfully encapsulated into the cavity of p(6SRA-5B) and its release was investigated in water and blood plasma by NMR, UV, CD, and fluorescence spectroscopy. The results show that the dissociation of the nanocarrier and the insulin release occurs with an increase in glucose concentration. At 5â mM glucose, the nanocarrier is stable, and the insulin release does not exceed 10 %. Increasing the glucose concentration to 7.5-10â mM results in a 40-100 % insulin release. p(6SRA-5B) is thus a promising insulin nanocarrier for the treatment of type 1 diabetes.
Subject(s)
Calixarenes/chemistry , Drug Carriers/chemistry , Drug Delivery Systems/methods , Glucose/pharmacology , Insulin/administration & dosage , Phenylalanine/analogs & derivatives , Boronic Acids/chemistry , Diabetes Mellitus, Type 1/drug therapy , Drug Liberation/drug effects , Humans , Phenylalanine/chemistry , Polymers/chemistry , Sulfonic Acids/chemistryABSTRACT
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.
Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Cations/chemistry , Fungi/drug effects , Pyridines/chemistry , Surface-Active Agents/pharmacology , Anti-Infective Agents/chemistry , Surface-Active Agents/chemistryABSTRACT
Novel polymer nanospheres (p(SRA-B)) were prepared by cross-linking a sulfonated resorcinarene (SRA) with phenylboronic acid. p(SRA-B) shows good stability in water and can be used as a nanocontainer for the pH- and glucose-controlled substrate release. Fluorescent dyes (fluorescein, pyrene and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt) were successfully loaded into p(SRA-B). The release of dye is achieved by lowering the pH value to 3 or by adding glucose.
ABSTRACT
In this communication we report the synthesis of Pd nanoparticle clusters achieved via the assembly of Pd nanoparticles on the surface of a spherical polymer network. The network exhibits flexibility and adapts to the cluster formation. The nanoclusters display high catalytic activity toward p-nitrophenol reduction and the Suzuki-Miyaura coupling reaction.
Subject(s)
Calixarenes/chemistry , Catalysis , Nanoparticles/chemistry , Polystyrenes/chemistry , Viologens/chemistry , Metal Nanoparticles , PalladiumABSTRACT
A novel class of self-assembling nanoparticles is formed with viologen-resorcin[4]arene cavitands; the association model is strongly controlled by their hydrophobicity. Interestingly, the cavitand assemblies are designed through click chemistry to form self-assembled noncovalently connected aggregates through counterion displacement. The iodide and benzoate ions are utilized as strongly polarizable counterions to induce cavitand self-assembly. The counterion-mediated decrease in hydrophilicity of the viologen-resorcin[4]arenes is the underlying trigger to induce particle formation. These particles can be used as nanocontainers and find their applications in delivery systems.
ABSTRACT
A pH-controlled photoinduced electron transfer in the supramolecular system [(Mo(6)Cl(8))L(6)]-calix[4]resorcine-dimethylviologen is reported.
