Calixarene Derivatives Research Articles

Silver loaded functionalized calix [4]arene nanofibers and evaluation in burn wound healing

Burn treatments with gene therapy and healing factors requires highly cost techniques. Instead, topical formulations including plant extract or pharmaceuticals are offered for wound-healing effect. However, these have low water solubility and cannot uptake into cells sufficiently. To overcome disadvantages, new effective treatment approaches should have been accessible. This study aimed to develop nanofiber-based wound coverings using four different Ag(I)-calixarene derivatives. Their nanofibers were produced by the electrospin method, and evaluated in vivo in rats with a second-degree burn model. Biochemical analysis has been maintained to exmine the effects of formulations on such as growth factors and some cytokines that are effective in wound healing process. In addition, histopathological analyzes has been performed to evaluate the presence and density of granulation tissue, inflammation, epithelial thickness and fibrosis. All data were compared with a commercial topical, silver sulfadiazine, whose usage is limited due to various disadvantages in the treatment processes of burn wounds. In this study, four different calixarene derivatives were synthesized their nanofibers were produced by the electrospin method, and their effectiveness was evaluated in vivo in rats with a second-degree burn model. Then, various biochemical and histopathological analyses were done to elucidate the possible wound-healing mechanism. When considering both pathological and biochemical data, the nanofibers of CLX-SAMD-Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(Sulfadiazine)‐26,28‐propylcalix (Xie and Unser, 2013) [4]arene - Ag) and CLX-MORF- Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(3-Morpholinopropil)‐26,28‐dihydroxycalix (Xie and Unser, 2013) [4]arene-Ag) were found to be more effective than silver sulfadiazine -silver content application, also known as traditional burn treatment for wound healing.

Recent Advances in Synthesis and Applications of Calixarene Derivatives Endowed with Anticancer Activity.

Calix[n]arenes, macrocycles constituted of 4-8 phenol moieties linked through methylene bridges, are stable molecules that can be selectively functionalised at the upper or lower rim. It has already been demonstrated that calixarene derivatives can be biologically or pharmacologically active compounds. More recently, suitably functionalised calixarenes and calixarene analogues (dihomooxacalixarenes, thiacalixarenes, calix[4]resorcinols, azacalixarenes, calixpyrroles, and pillarenes) were found to act as anticancer agents, at least in in vitro assays. We are reporting on the latest progress in this research field.

Identification of Potential Drug Targets of Calix[4]arene by Reverse Docking.

Calixarenes are displaying great potential for the development of new drug delivery systems, diagnostic imaging, biosensing devices and inhibitors of biological processes. In particular, calixarene derivatives are able to interact with many different enzymes and function as inhibitors. By screening of the potential drug target database (PDTD) with a reverse docking procedure, we identify and discuss a selection of 100 proteins that interact strongly with calix[4]arene. We also discover that leucine (23.5 %), isoleucine (11.3 %), phenylalanines (11.3 %) and valine (9.5 %) are the most frequent binding residues followed by hydrophobic cysteines and methionines and aromatic histidines, tyrosines and tryptophanes. Top binders are peroxisome proliferator-activated receptors that already are targeted by commercial drugs, demonstrating the practical interest in calix[4]arene. Nuclear receptors, potassium channel, several carrier proteins, a variety of cancer-related proteins and viral proteins are prominent in the list. It is concluded that calix[4]arene, which is characterized by facile access, well-defined conformational characteristics, and ease of functionalization at both the lower and higher rims, could be a potential lead compound for the development of enzyme inhibitors and theranostic platforms.

Synthesis and Spectral Properties of Conjugated Bis-1,3-diketo Derivatives of Calix[4]arene in the 1,3-alternate Isomeric Form and Their Complexes with Eu3+

Distally substituted bis-1,3-diketone derivatives of calix[4]arene were synthesized, in which chelate groups are attached via a carbonyl carbon atom to the p-positions of phenolic fragments of a macrocycle fixed in 1,3-alternate isomeric form. 1,3-Diketone derivatives were obtained by acylation of magnesium enolate of a calix[4]arene ketone with 1-benzoylbenzotriazoles. In the synthesized compounds, 1,3-diketone groups are conjugated with the π-aromatic system of calix[4]arene. It was found by means of UV spectroscopy and NMR diffusion methods in combination with quantum chemical (DFT) calculations that a mononuclear complex with bis-chelate coordination of the lanthanide ion is predominantly formed in the solution. The formation of the complex leads to a decrease in the conjugation degree in the ligand. The most effective sensitization of Eu3+ luminescence, compared to the p-F- or p-CF3-phenyl-substituted complexes is observed for calix[4]arene complexes with H-phenyl-substituted 1,3-diketone groups.

PAHs removal by soil washing with thiacalix[4]arene tetrasulfonate

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods—chemical, thermal, and bioremediation—along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

Supramolecular Logic Gates Based on the Conjugates of Calixarenes and Carbohydrates.

In the era of application-oriented research, laboratory to real life translation is highly regarded and in great demand. This could mean that molecular science developed for sensing and detecting a variety of chemical species awaits conversion to devices. In that, the molecular logic gates are the most promising ones where the information storage and/or data processing can be easily carried out in terms of molecular inputs and electrical response outputs. This would facilitate the simultaneous execution of a diverse array of molecular sensing functions. The recent progress in molecular logic gates based on supramolecular optical receptors, in particular, fluorescent ones, such as calixarene derivatives and carbohydrate conjugates will have a transformative impact on molecular devices and will encourage this science to yield technology. Therefore, this review provides a critical evaluation of recent publications on molecular logic gates based on the derivatives of calixarenes and glyco-conjugates, including several from our own research group, with the view that the corresponding applications are a beneficiary in laboratory-to-device translation. In addition, this review is also expected to assist young researchers in planning their research focus in the broad area of supramolecular-based logic gates targeting some specific applications.

Calixarene: A Supramolecular Material for Treating Cancer.

Cancer is a disease with a high mortality rate; therefore, research on new treatment strategies is essential. There has been increased interest in novel drug delivery systems (DDS) in recent years, such as calixarene, one of the most important principal molecules in supramolecular chemistry. Calixarene is a cyclic oligomer of phenolic units linked by methylene bridges that belongs to the third generation of supramolecular compounds. By modifying the phenolic hydroxyl end (lower edge) or the para-position, a wide range of calixarene derivatives can be obtained (upper edge). Drugs are combined with calixarenes to modify and have new properties, such as strong water solubility, the ability to bond with guest molecules, and excellent biocompatibility. In this review, we summarize the applications of calixarene in the construction of anticancer drug delivery systems and its application in clinical treatment and diagnosis. It provides theoretical support for the diagnosis and treatment of cancer in the future.

含氮有机物修饰的杯芳烃类衍生物的生物活性

含氮有机物修饰的杯芳烃类衍生物的生物活性

Enhancing the Cation-Binding Ability of Fluorescent Calixarene Derivatives: Structural, Thermodynamic, and Computational Studies.

Novel fluorescent calix[4]arene derivatives L1 and L2 were synthesized by introducing phenanthridine moieties at the lower calixarene rim, whereby phenanthridine groups served as fluorescent probes and for cation coordination. To enhance the cation-binding ability of the ligands, besides phenanthridines, tertiary-amide or ester functionalities were also introduced in the cation-binding site. Complexation of the prepared compounds with alkali metal cations in acetonitrile (MeCN), methanol (MeOH), ethanol (EtOH), N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) was investigated at 25 °C experimentally (UV spectrophotometry, fluorimetry, microcalorimetry, and in the solid state by X-ray crystallography) and by means of computational techniques (classical molecular dynamics and DFT calculations). The thermodynamic parameters (equilibrium constants and derived standard reaction Gibbs energies, reaction enthalpies, and entropies) of the corresponding reactions were determined. The tertiary-amide-based compound L1 was found to have a much higher affinity toward cations compared to ester derivative L2, whereby the stabilities of the ML1+ and ML2+ complexes were quite solvent-dependent. The stability decreased in the solvent order: MeCN ≫ EtOH > MeOH > DMF > DMSO, which could be explained by taking into account the differences in the solvation of the ligands as well as free and complexed alkali metal cations in the solvents used. The obtained thermodynamic quantities were thoroughly discussed regarding the structural characteristics of the studied compounds, as well as the solvation abilities of the solvents examined. Molecular and crystal structures of acetonitrile and water solvates of L1 and its sodium complex were determined by single-crystal X-ray diffraction. The results of computational studies provided additional insight into the L1 and L2 complexation properties and structures of the ligands and their cation complexes.

Separation of methionine and arginine onto calix[4]arene grafted Merrifield resin

Based on host–guest complexation and a utilizing a functionalized Merrifield resin, a practical method was developed to separate methionine and arginine mixtures. To obtain the resin, a new derivative of calix[4]arene was immobilized on Merrifield resin. The resin was recyclable and it was used for several times for rapid and convenient separation of amino acids from the mixtures mentioned above.

Aggregation, Cytotoxicity and DNA Binding in a Series of Calix[4]arene Amphiphile Containing Aminotriazole Groups.

The present work focuses on the study of the aggregation and complexing properties of calixarenes as potential DNA condensation agents for gene delivery. In the current study, 1,4-triazole derivatives of calix[4]arenes 7 and 8 containing monoammonium fragments were synthesized. The synthesized compound's structure was characterized by using various spectroscopic techniques (FTIR, HRESI MS, ¹H NMR and ¹³C NMR). The interactions between a series of calix[4]arene-containing aminotriazole groups (triazole-containing macrocycles with diethylenetriammonium fragments (3 and 4) and triazole-containing macrocycles with monoammonium fragments (7 and 8)) and calf thymus DNA were carried out via UV absorption, fluorescence spectroscopy, dynamic light scattering and zeta potential measurements. The role of the binding forces of calixarene-DNA complexes was analyzed. Photophysical and morphological studies revealed the interaction of the calixarenes 3, 4 and 8 with ct-DNA, which transformed the fibrous structure of ct-DNA to completely condensed compact structures that are 50 nm in diameter. The cytotoxic properties of calixarenes 3, 4, 7 and 8 against cancerous cells (MCF7, PC-3) as well as a healthy cell line (HSF) were investigated. Compound 4 was found to have the highest toxic effect on MCF7 breast adenocarcinoma (IC50 3.3 μM).

Design of screen-printed potentiometric platform for sensitive determination of mirabegron in spiked human plasma; molecular docking and transducer optimization.

The integration of molecular modelling simulation and electrochemical sensors is of high interest. Herein, for the first time, a portable solid-contact potentiometric electrode was designed for the sensitive determination of mirabegron (MIR) in human plasma and pharmaceutical formulation. A two-step optimization protocol was investigated for the fabrication of an ion on sensing polymeric membrane. First, molecular docking was used for optimum ionophore selection. Calix[6]arene showed the highest affinity towards MIR with a better docking score (-4.35) and potential energy (-65.23) compared to other calixarene derivatives. Second, carbon nanotubes and gold nanoparticles were investigated as ion-electron transducers using a drop-casting procedure. Gold nanoparticle-based sensors showed better slope, potential stability, and rapid response compared to carbon nanotubes. The proposed solid contact sensors (V-VII) showed comparable sensitivity and ease of handling compared to liquid contact sensors (I-IV). The optimized gold nanoparticles sensor VII produced a Nernstian response over the range of 9.77 × 10-7 to 1 × 10-3 M with LOD of 2.4 × 10-7 M. It has also been used to determine MIR in its pharmaceutical formulation in the presence of a co-formulated antioxidant butylated hydroxytoluene and spiked human plasma. This would offer a feasible and economic platform for monitoring MIR in pharmaceutical preparation and biological fluids.

Oxyethylated Fluoresceine—(thia)calix[4]arene Conjugates: Synthesis and Visible-Light Photoredox Catalysis in Water–Organic Media

Fluorescent derivatives attract the attention of researchers for their use as sensors, photocatalysts and for the creation of functional materials. In order to create amphiphilic fluorescent derivatives of calixarenes, a fluorescein derivative containing oligoethylene glycol and propargyl groups was obtained. The resulting fluorescein derivative was introduced into three different (thia)calix[4]arene azide derivatives. For all synthesized compounds, the luminescence quantum yields have been established in different solvents. Using UV-visible spectroscopy, dynamic light scattering, as well as transmission and confocal microscopy, aggregation of macrocycles was studied. It was evaluated that calixarene derivatives with alkyl substituents form spherical aggregates, while symmetrical tetrafluorescein-containing thiacalix[4]arene forms extended worm-like aggregates. The macrocycle containing tetradecyl fragments was found to be the most efficient in photoredox ipso-oxidation of phenylboronic acid. In addition, it was shown that in a number of different electron donors (NEt3, DABCO and iPr2EtN), the photoredox ipso-oxidation proceeds best with triethylamine. It has been shown that a low molecular weight surfactant Triton-X100 can also improve the photocatalytic abilities of an oligoethylene glycol fluorescein derivative, thus showing the importance of a combination of micellar and photoredox catalysis.

Unconventional OFF-ON Response of a Mono(calix[4]arene)-Substituted BODIPY Sensor for Hg2+ through Dimerization Reversion.

A new selective fluorogenic chemosensor for Hg2+, which combines a calixarene derivative with a BODIPY core as a fluorescent reporter, is described. The remarkable change in its fluorogenic properties in DMSO and CHCl3 has been analyzed. A study of its spectral properties on dilution, along with molecular modeling studies, allowed us to explain that this behavior involves the formation of a J-dimer, as well as how the sensing mechanism of Hg2+ proceeds.

Calixarene Functionalized Supramolecular Liquid Crystals and Their Diverse Applications.

Liquid crystals are considered to be the fourth state of matter with an intermediate order and fluidity in comparison to solids and liquids. Calixarenes are among one of the most versatile families of building blocks for supramolecular chemistry due to their unique vaselike structure that can be chemically engineered to have different shapes and sizes. During the last few decades, calixarenes have drawn much attention in the field of supramolecular chemistry due to their diverse applications in the fields of ion and molecular recognition, ion-selective electrodes for catalysis, drug delivery, gelation, organic electronics and sensors, etc. Imbuing liquid crystallinity to the calixarene framework leads to functionalized calixarene derivatives with fluidity and order. Columnar self-assembly of such derivatives in particular enhance the charge migration along the column due to the 1D stacking due to the enhanced π-π overlap. Considering limited reports and reviews on this new class of calixarene based liquid crystals, a comprehensive account of the synthesis of calixarene liquid crystals along with their mesomorphic behavior and potential applications are presented in this review.

Theoretical studies of calixarene derivatives as receptors for transition metals

The behavior of a calixarene derivative – p–tert butyl calix[4]arene (TBC4) – as receptor for transition metals (Cr, Ni, Cd) has been investigated by density functional calculations. Particular attention has been paid to the energetics and the nature of the metal–TBC4 interactions. Our results predict, that TBC4 should be a good receptor for the extraction of Ni, due to the strong interactions between Ni and the cone-shaped part of the organic molecule in comparison with Cd and Cr.

Synthesis, characterization, and computational study of aggregates from amphiphilic calix[6]arenes. Effect of encapsulation on degradation kinetics of curcumin

The aggregation behaviour of two tris(N-phenylureido)-calixarene derivatives, bearing three octyl chains at the lower rim and differing from each other for the absence or presence of ionizable carboxyl groups at the upper rim, has been investigated. Aggregates from both calixarenes have been obtained by the emulsion/solvent evaporation method and characterized by a combination of complementary techniques (DLS, SEM and AFM). Critical aggregation concentration has also been determined. The calixarene not bearing carboxyl groups forms aggregates in which the hydrophilic dye Rhodamine B can be loaded. The aggregate stability toward disassembly was evaluated in terms of rate of spontaneous and TX-100 induced release of entrapped Rhodamine. Both calixarene aggregates entrap the hydrophobic drug curcumin and improve its water solubility. The effect of encapsulation on the kinetics of photodegradation and alkaline hydrolysis of curcumin has been evaluated. Molecular dynamics simulations were also carried out to support the experimental results concerning the morphology of the aggregates.

A novel material based on an antibacterial choline-calixarene nanoassembly embedded in thin films

Supramolecular chemistry is one of the current strategies for producing advanced materials. With the aim to develop new Thin-Films with antibacterial activity, we embedded an amphiphilic choline-calix[4]arene possessing antibacterial properties in polymeric Thin-Films based on polyether-co-amide matrix (Pebax®2533). The loading of the calix[4]arene derivative in the film was performed by solution casting. The amount of calixarene additive in the films was in the range of 0.5–5 wt%. The self-supported Thin-Films were characterized by investigating phase miscibility, morphology, spectral properties, and gas transport. The release of the calixarene derivative from the films was studied in a biomimetic medium as PBS (10 mM, pH 7.4). The presence of the additive did not affect the thermal stability of the copolymer, whereas it induced an increase in crystallinity, wettability, and gas permeability of the blend films according to its concentration. The antibacterial activity of the films was evaluated in vitro against Escherichia coli and Staphylococcus aureus strains, representative of Gram-negative and Gram-positive bacteria. The developed films displayed antibacterial activity against both strains. In particular, Pebax® − 5 wt% Chol-Calix caused within 10 h a reduction in E. coli and S. aureus of 2.57 and 2 log CFU/mL, respectively. The potential toxicity of the films was also tested on mouse embryonic fibroblasts NIH/3T3. Pebax®2533/calixarene derivative combination appears a promising approach for the development of novel flexible antibacterial materials.Graphical abstract

Synthesis of optically pure calix[4]arenes derived from Evans oxazolidinone and/or pyranose

Eight new optically pure calixarene derivatives, in which their lower rims were substituted with Evans oxazolidinone or pyranose moieties, are described. All macrocycles were fully characterized by NMR spectroscopy, optical rotation, and elemental analysis. The introduction of chiral auxiliaries reduced the symmetry of the macrocycle as observed by NMR. Stereospecific alkylation on the Evans oxazolidinone moiety allowed the asymmetric introduction of a methyl substituent near a phenolic position of the macrocycle.

Design, Synthesis, Electronic Properties, and X-ray Structural Characterization of Various Modified Electron-Rich Calixarene Derivatives and Their Conversion to Stable Cation Radical Salts.

We have designed and synthesized electron-rich calixarene derivatives, which undergo reversible electrochemical oxidation in a well-accessible potential range that allows the ready preparation and isolation of the corresponding cation radicals. Preparation of mono- or tetra-radical cation can be achieved by using stable aromatic cation-radical salts such as MA+•, MB+•, and NAP+• as selective organic oxidants. The cation radicals of calixarenes are stable indefinitely at ambient temperatures and can be readily characterized by UV-vis-NIR spectroscopy. These cation radicals bind a single molecule of nitric oxide within its cavity with remarkable efficiency.