Synthesis, fluorescent properties and aggregation of 2,3-dihydroisoindolenylcalix[4]arenes

New derivatives of calix[4]arenes, containing two isoindole fragments in distal positions of the macrocycle upper rim were synthesized. According to NMR and molecular modeling data, the obtained calixarenes exist in “flattened cone” conformation with inclination angles of benzene rings to the macrocycle plane equal to 133–140° and 92–100°. Fluorometric studies showed the presence of self-aggregation of isoindolenylcalixarenes in acetone solutions starting from micromolar concentrations.     

Surface activity and self-aggregation ability of three cationic quaternized aminocalix[4]arenes

The self-aggregation ability of three amphiphilic cationic calix[4]arenes possessing four quaternary amino groups (aminoCAs) was investigated using a variety of methods. All of the studied compounds possess high aggregation ability. Their critical aggregation concentration (CAC) values in water are in the 0.0009–0.04 % (w/v) concentration range. Several size populations of aggregates were detected by DLS for all three CAs, and restructuring of aggregates was observed to be dependent on concentration. Particles formed above CAC were attributed to formation of vesicular structures (vesicles). The coexistence of other type of aggregates (presumably micelles) with vesicles was observed in the aqueous solution of CAs 2 and 3 from concentrations of 0.5 and 0.8 % (w/v), respectively. The filtration procedure was found to be a significant factor since the obtained data from filtered and unfiltered samples was different. The particle sizes obtained by TEM measurements were somewhat correlated with the DLS data for unfiltered CAs solutions. An analysis of the aggregate composition was undertaken by a size-exclusion method using semi-permeable cellophane membranes with different MWCO. A negative deviation from linearity of permeability flux profile starting from 0.8 % (w/v) concentration of donor phase indicated that the fraction of large aggregates at this point is significant enough that the molecules could not easily permeate through the membranes.     

Protein‐Sized Bright Fluorogenic Nanoparticles Based on Cross‐Linked Calixarene Micelles with Cyanine Corona

The key challenge in the field of fluorescent nanoparticles (NPs) for biological applications is to achieve superior brightness for sizes equivalent to single proteins (3–7 nm). We propose a concept of shell‐cross‐linked fluorescent micelles, in which PEGylated cyanine 3 and 5 bis‐azides form a covalently attached corona on micelles of amphiphilic calixarene bearing four alkyne groups. The fluorescence quantum yield of the obtained monodisperse NPs, with a size of 7 nm, is a function of viscosity and reached up to 15 % in glycerol. In the on‐state they are circa 2‐fold brighter than quantum dots (QD‐585), which makes them the smallest PEGylated organic NPs of this high brightness. FRET between cyanine 3 and 5 cross‐linkers at the surface of NPs suggests their integrity in physiological media, organic solvents, and living cells, in which the NPs rapidly internalize, showing excellent imaging contrast. Calixarene micelles with a cyanine corona constitute a new platform for the development of protein‐sized ultrabright fluorescent NPs.     

Calixarenes functionalized with phosphine oxide and diamide functions as extractants and ionofores for rare-earth metals

Calixarene-based ligands with phosphine oxide and diamide functions at wide and narrow rims are synthesized and studied as extracting agents for liquid extraction and ionophores for polymeric electrochemical ion sensors. Calixarene ligands are compared with corresponding phosphine oxide and diamide ligands which are not attached to the calixarene platform. Extraction and sensor properties of the ligands were studied in different metal ion solution with special attention paid to rare-earth metals. Attachment of phosphine oxide groups to the calixarene platform leads to the sharp increase of both extraction and sensing ability of the corresponding systems comparing to non-bonded phosphine oxide. In case of the diamide derivatives attached to the calixarene performance of corresponding ligands was similar to those of non-bonded diamides.     

Tetrazolecalix[4]arenes as new ligands for palladium(II)

The synthesis of new calix[4]arenes bearing two or four tetrazole liganting groups at the upper rim is decribed. The structures of tetrakis-tetrazolecalix[4]arene and its palladium dichloride (2:2) complex are examined by X-ray crystallography.     

Surface Modification of Aminopropylated Silica Gel with Tetraphosphorylated bis-Methoxycarbonylmethoxycalix[4]Arenes for Effective Europium(Iii) Sorption

Theoretical and Experimental Chemistry - bis-Methoxycarbonylmethoxy derivatives capable of reacting with the surface of aminopropylated silica gel with the formation of chemically and thermally...     

Virus-sized DNA nanoparticles for gene delivery based on micelles of cationic calixarenes

Macrocyclic amphiphilic molecules based on calix[4]arenes are highly attractive for controlled supramolecular assembly of DNA into small nanoparticles, since they present a unique conical architecture and can bear multiple charged groups. In the present work, we synthesized new amphiphilic calixarenes bearing cationic groups at the upper rim and alkyl chains at the lower rim. Their self-assembly in aqueous solution was characterized by fluorescent probes, fluorescence correlation spectroscopy, dynamic light scattering, gel electrophoresis and atomic force microscopy. We found that calixarenes bearing long alkyl chains (octyl) self-assemble into micelles of 6 nm diameter at low critical micellar concentration and present the unique ability to condense DNA into small nanoparticles of about 50 nm diameter. In contrast, the short-chain (propyl) analogues that cannot form micelles at low concentrations failed to condense DNA, giving large polydisperse DNA complexes. Thus, formation of small DNA nanoparticles is hierarchical, requiring assembly of calixarenes into micellar building blocks that further co-assemble with DNA into small virus-sized particles. The latter showed much better gene transfection efficiency in cell cultures relative to the large DNA complexes with the short-chain analogues, which indicates that gene delivery of calixarene/DNA complexes depends strongly on their structure. Moreover, all cationic calixarenes studied showed low cytotoxicity. Thus, this work presents a two-step hierarchical assembly of small DNA nanoparticles for gene delivery based on amphiphilic cone-shaped cationic calixarenes.     

Calix[4]arenesulfonylamidines. Synthesis, structure and influence on Mg, ATP-dependent calcium pumps

Calix[4]arenes, functionalized at the wide rim with two or four N²-sulfonylamidine groups were prepared. In the crystalline state, the bowl shaped calix[4]arene-bis-N-sulfonyltrifluoromethylacetamidine 3b is associated through intermolecular hydrogen bonds, NH?OS, while the phenyl rings of the Ph-SO₂-fragments are hosted in the cavities of the nearby molecules of 3b. Calixarene 4b influences Ca²⁺ transport in Mg²⁺, ATP-dependent calcium pumps.     

Calixarenes and related macrocycles as gene delivery vehicles

The success of gene therapy depends largely on the development of new efficient gene delivery vehicles. The emerging class of molecules for this application is macrocycles that feature persistent shape, thus ensuring higher level of supramolecular organization of the DNA complexes. The review focuses on recently developed calixarenes and close analogues as gene delivery vectors, their chemistry, ability to compact nucleic acids, transfection ability in vitro and cytotoxicity. Their fixed conformation with the possibility of multiple functional groups at the upper and lower rims allows preparation of cone-shaped macromolecules capable of programmed hierarchical assembly in the presence of DNA. It is shown that specially designed calixarenes, particularly those having amphiphilic structure with clustered DNA binding units, can form small virus-sized DNA nanoparticles with well-defined architecture, high transfection efficiency and low toxicity. The field is still largely underexplored so that there is a lot of room for further improvement of the molecular design of calixarenes. Moreover, their evaluation in vivo on animals will be an important step towards their validation for gene therapy.     

Calix[4]arenequinazolinones. Synthesis and structure

The synthesis of calix[4]arenes bearing two quinazolin-4-ones group at the upper rim is decribed. ¹H NMR spectra and quantum chemical calculations make it possible to suggest that calix[4]arenequinazolinones form three rotamers in solutions at room temperature, due to the restricted rotation of the quinazolinone fragments. The X-ray structure investigation indicates that quinazolin-4-onecalix[4]arene exists in the crystal state as the methanol 1:1 inclusion complex.