Calixarene Derivatives Research Articles

A highly selective fluorescence probe for Co2+ or Cu2+ detection based on a new tetraquinoline-substituted calix[4]arene derivative

A new calixarene derivative (AlQuin-Calix) bearing two quinoline groups at its lower rim was synthesized at cone conformation. Then, upon functionalization of AlQuin-Calix with two more quinoline groups resulted with a novel calixarene-based fluorescent chemosensor (TetQuin-Calix) at partial cone conformation. The structures of all calixarene derivatives were duly characterized by spectroscopic methods such as FTIR, 1H NMR, 13C NMR, ESI-MS and elemental analysis. Moreover, ion sensing properties of AlQuin-Calix and TetQuin-Calix against different cations such as Co2+, Cu2+, Ni2+, Zn2+ and Ba2+ were evaluated. It was found that the calixarene-based chemosensor (TetQuin-Calix) exhibits remarkable affinity and high selectivity for Cu2+ and Co2+ in 50% water-CH3CN, while AlQuin-Calix provides an efficient chemosensor property towards only Co2+ ion among others. The fluorescence of TetQuin-Calix, with excitation/emission peaks at 268/397 nm, is quenched by Cu2+ or Co2+ ions. The limits of detection of TetQuin-Calix for Cu2+ and Co2+ ions were estimated to be 0.75 and 0.72 μM, respectively. Besides, stoichiometry, and binding constant in terms of the quenching mechanism were also determined using fluorescence data.

A facile and effective immunoassay for sensitive detection of phosphorylated tau: The role of flower-shaped TiO2 in specificity and signal amplification

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disease. Plasma total phosphorylated tau (P-tau) with multi-phosphorylation sites is a potentially efficient biomarker for the diagnosis and prognosis of AD. Single phosphorylation site recognition methods lead to the false positive detection of P-tau and decrease the accuracy of AD analysis. In this work, a simple and precise electrochemical immunoassay was developed for the specific detection of P-tau. Calixarene derivative ProLinker was utilized to orient Anti-tau onto the surface of gold electrode. ProLinker provide abundant binding sites for immobilized antibodies via host-guest recognitions and ensure Anti-tau activity through non-covalent interactions. Flower-shaped TiO2 (F-TiO2) forming coordination bonds with the phosphate group of phosphorylated protein were utilized as signal amplification tags to construct a simple sandwich assay for multiple phosphorylated sites sensing of P-tau. The combination of F-TiO2 and Anti-tau ensured the bispecific and precise recognition of P-tau with a wide detection range (1–200 ng/mL) and a low detection of limit (1.774 pg/mL). With large specific surface area, high electron hinder ability, and great stability, F-TiO2 as an amplification molecule can improve the performance of the immunosensor and produce sensitive signal changes according to the concentration of P-tau in the clinical samples. Hence, this P-tau immunoassay paves the way for the development of efficient detection tools for clinical diagnosis and monitoring.

Novel edifice calix[4]pyrrole derivatives as a potential sensor for the detection of analytes and in silico computational behaviour

The beguiling properties of functionalised calix[4]pyrrole has garnered a lot of attention due to its selective and specific sensitivity towards biomolecules and cations, it behaves as a frontline contender for recognition moieties and their eventual applications as fluorogenic sensing agents have received increasing interest. The binding properties of calix[4]pyrrole can be modulated by diverse structural modifications or by the change of solvent. Accessibility, high fluorescence quantum yield, and biological activity of aminoanthraquinone and aminoquinoline has attracted as a fluorophore, polymer additives and medicinal agents. Due to the tunable properties of aminoanthraquinone and aminoquinoline and calix[4]pyrrole scaffold fixing up may lead to development of new sensor. In this regards we have synthesised two derivatives of calix[4]pyrrole bearing carboxylic group i.e. ABCPTAA & ABCPTAQ which binds selectively with OTC and Hg(II) ions, respectively. The experimental data are very well supported by spectroscopic as well as computational studies.

EFFICIENT AND SELECTIVE ANTITUMOR AGENTS BASED ON CATIONIC CALIXARENES: SYNTHESIS, CHARACTERIZATION, AND ANTIPROLIFERATIVE PROPERTIES

Research work on the preparation of anti-tumor agents with active properties is still a major field for the pharmaceutical industry to promote more potent anticancer drugs to the market. However, one of the main disadvantages of current and future anticancer drugs is selectivity. Therefore, in recent decades, a new perspective has to be developed for chemotherapy, such as "targeted" drugs and minimal side effects. Calixarenes, composed of phenolic units linked by methylene bridges are versatile kinds of macrocyclic compounds in supramolecular chemistry that can be modified to hydrophilic and hydrophobic cavities. The biocompatibility of calixarene derivatives allows them to be used in the development of in vivo and in vitro applications. For this reason, the calixarenes with different active groups, have been synthesized by many researchers as a target structure, and their biological activities and in particular their anti-cancer properties, have been studied. The purpose of the current study is to synthesize calix[4]arene derivatives bearing the cationic group at the lower rim and investigation their cytotoxic effect for several cancerous cells. Results demonstrated that calix[4]arene derivative having 5-bromopenty trimethylammonium bromide moieties (CN) and calix[4]arene derivative having 3-bromopropyl-triphenylphosphonium bromide moieties (CP) compounds selectively inhibits proliferation of A549 (13.42 µM) and HeLa (17.05 µM) and Hep-2 cells (>200 µM and 162.71 µM), respectively.

Colorimetric detection of sulfamethazine based on target resolved calixarene derivative stabilized gold nanoparticles aggregation.

Sulfamethazine (SMZ) is one of the most used broad-spectrum antibiotics owing to its low cost and high efficacy towards bacterial diseases. This workreportsa novel label-free SMZ sensor based on para-sulfonatocalix[4]arene (pSC4) capped gold nanoparticles (pSC4-AuNPs) for colorimetric detection through the host-guest interaction. The existence of SMZ resulted in the aggregation of pSC4-AuNPs and canbe observed through colorimetric assay. A good linear relationship in the range 2.5 ~ 20nM was obtained with a correlation coefficient of 0.9908. The limit of detection for SMZ was 1.39nM. High recoveries (90.18-107.06%) were obtained, and RSD ranged from 1.21 to 2.05%. The color changes can be observed from red to gray within 10min. Combining the supermolecule's recognition and AuNP's optical performance, the method paves a new, easy, and rapid way for small target sensing.

Review on Calixarene Fluorescent Chemosensor Agents for Various Analytes

Calixarenes are well-known supramolecular host molecules with versatile applications. Over the past decades, hundreds of selective and sensitive detections of several analytes have been reported by employing calixarenes as the chemosensor agent. The detection and quantification of metal ions and anions are crucial as heavy metal ions are harmful to living organisms, while monitoring anions is pivotal in the environmental samples. On the other hand, detecting and quantifying biomolecules and neutral molecules are critical due to their irreplaceable role in human health. In this review, we summarized the application of calixarenes as the supramolecular chemosensor agent for detecting metal ions, anions, biomolecules, and neutral molecules through fluorescent spectroscopy to give brief information on the design and development of the chemosensor field. This review updates the world with the application of calixarene derivatives as fluorescent chemosensors and challenges researchers to design and develop better chemosensor agents in the future.

The Role of Triazole and Glucose Moieties in Alkali Metal Cation Complexation by Lower-Rim Tertiary-Amide Calix[4]arene Derivatives.

The binding of alkali metal cations with two tertiary-amide lower-rim calix[4]arenes was studied in methanol, N,N-dimethylformamide, and acetonitrile in order to explore the role of triazole and glucose functionalities in the coordination reactions. The standard thermodynamic complexation parameters were determined microcalorimetrically and spectrophotometrically. On the basis of receptor dissolution enthalpies and the literature data, the enthalpies for transfer of reactants and products between the solvents were calculated. The solvent inclusion within a calixarene hydrophobic basket was explored by means of 1H NMR spectroscopy. Classical molecular dynamics of the calixarene ligands and their complexes were carried out as well. The affinity of receptors for cations in methanol and N,N-dimethylformamide was quite similar, irrespective of whether they contained glucose subunits or not. This indicated that sugar moieties did not participate or influence the cation binding. All studied reactions were enthalpically controlled. The peak affinity of receptors for sodium cation was noticed in all complexation media. The complex stabilities were the highest in acetonitrile, followed by methanol and N,N-dimethylformamide. The solubilities of receptors were greatly affected by the presence of sugar subunits. The medium effect on the affinities of calixarene derivatives towards cations was thoroughly discussed regarding the structural properties and solvation abilities of the investigated solvents.

Novel oxadiazole- and triazole-based calixarene derivatives: synthesis and extraction properties

Two new calixarene derivative compounds bearing oxadiazole and triazole groups were synthesized. The final products were illuminated by using 1H-NMR, 13C-NMR, FT-IR and HR-MS. The extraction efficiency of these compounds was investigated in the removal of methyl orange. In addition, the effect of H+ ion concentration in extraction studies conducted in different pH ranges and the effect of NaCl concentration on the percentage of extraction was examined. The results obtained showed that the percentage of extraction was highly dependent on the H+ ion concentration. It was found that the percentage of methyl orange removal was 53.3% for triazole derivatives 5.

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition.

Carbonic anhydrases (CAs) continue to represent a relevant pharmaceutical target. The need of selective inhibitors and the involvement of these metalloenzymes in many multifaceted diseases boost the search for new ligands able to distinguish among the different CA isoforms, and for multifunctional systems simultaneously able to inhibit CAs and to interfere with other pathological events by interacting with additional targets. In this work, we successfully explored the possibility of preparing new CAs ligands by combining calixarenes with benzensulfonamide units. Inhibition tests towards three human CA isoforms evidenced, for some of the ligands, Ki values in the nanomolar range and promising selectivity. X-ray and molecular modeling studies provided information on the mode of binding of these calixarene derivatives. Thanks to the encouraging results and the structural features typical of the calixarene scaffold, it is then possible to plan for the future the design of multifunctional inhibitors for this class of widely spread enzymes.

Spectroscopic characterization, host-guest charge transfer, Hirshfeld surfaces, AIM-RDG and ELF study of adsorption and chemical sensing of heavy metals with new derivative of Calix [4]quinone: A DFT-D3 computation

Attributing to the chemical sensor application based on charge transfer phenomena between the host and the guest for new derivative of calix [4]quinone, 1,3-alternate-calix [4]quinone (C4Q), have been investigated via DFT-D3 calculation and compared to the experimental data. The structural design of the title molecule has been characterized, and the organic quinone has been clearly identified. The selected sites for the Cu2+, Ag2+ and Hg2+ cations by the calix [4]quinone molecule have been discussed. The molecular electrostatic potential (MEP) map has been performed in order to identify the highly attractive site for the selected cations. The 1H NMR chemical shifts of the stable complexes have been calculated. Moreover, the calculated stretching vibrational modes in the most stable conformations have been assigned and compared with the experimental ones. The UV–Vis spectroscopy revealed that the interaction of the Cu2+, Ag2+ (d9 electron configuration) and Hg2+(d10 electron configuration) cations with the C4Q is reinforced with the red shifting to high absorption bands of the free molecule. The HOMO and LUMO orbital iso-surfaces exhibit that the C4Q-Cu2+ complex has the highest charge transfer terms (CTT) which increased the overall energetic stabilization of the system. The Hirshfeld surface (HS) showed the highly attractive energetic binds that favor the efficient charge transfer phenomena between the two systems. The interactions between the host (C4Q) and guest (metal cation) are discussed deeply using the topological AIM and non-covalent RDG index analyses. The computed values from electron density and the binding energies for all active bonds have been interpreted. Finally, the ELF/LOL at bond critical points and ELF maps are computed to confirm and visualize the donor-acceptor couple formed between the selected host-guest systems.

Conformationally tunable calix[4]pyrrole-based nanofilms for efficient molecular separation

Preparation of nanofilms which are able to reject water-soluble low molecular weight organic compounds in nanofiltration remains to be a challenge. Herein, we report a new kind of self-standing, defect-free, robust, centimeter-sized and thickness controllable calix[4]pyrrole (C[4]P)-based nanofilms with excellent molecular sieving performance in nanofiltration. The nanofilms were prepared via confined dynamic condensation of the tetra-benzoyl-hydrazine derivative of calix[4]pyrrole (CPTBH) with 1,3,5-benzenetricarboxaldehyde (BTC) at the air/dimethyl sulfoxide (DMSO) interface. Nanofiltration tests under 2 bar pressure with porous polyethylene terephthalate (PET) as the support and a CsF treated CPTBH-BTC nanofilm (∼100 nm) as the selective layer depicted a water permeance of 15 L m-2h−1 bar−1 and a methanol permeance of 45 L m-2h−1 bar−1. High rejection rates (>95%) were found in aqueous solution for most of the tested dyes and pharmaceuticals. Remarkably, the composite membrane also demonstrated good separation performance in aqueous phase to some amino acids and organic dyes with molecular weights around 200 g/mol. High-performance nanofiltration in methanol was also realized. In this case, the molecular weight cutoff value is ∼ 800 g/mol. These findings showed that introduction of macrocyclic hosts is an effective way to develop nanofilms with high solvent permeance but low molecular weight cutoff value.

Single Excited Dual Band Luminescent Hybrid Carbon Dots-Terbium Chelate Nanothermometer.

The report introduces hybrid polyelectrolyte-stabilized colloids combining blue and green-emitting building blocks, which are citrate carbon dots (CDs) and [TbL]+ chelate complexes with 1,3-diketonate derivatives of calix[4]arene. The joint incorporation of green and blue-emitting blocks into the polysodium polystyrenesulfonate (PSS) aggregates is carried out through the solvent-exchange synthetic technique. The coordinative binding between Tb3+ centers and CD surface groups in initial DMF solutions both facilitates joint incorporation of [TbL]+ complexes and the CDs into the PSS-based nanobeads and affects fluorescence properties of [TbL]+ complexes and CDs, as well as their ability for temperature sensing. The variation of the synthetic conditions is represented herein as a tool for tuning the fluorescent response of the blue and green-emitting blocks upon heating and cooling. The revealed regularities enable developing either dual-band luminescent colloids for monitoring temperature changes within 25–50 °C through double color emission or transforming the colloids into ratiometric temperature sensors via simple concentration variation of [TbL]+ and CDs in the initial DMF solution. Novel hybrid carbon dots-terbium chelate PSS-based nanoplatform opens an avenue for a new generation of sensitive and customizable single excited dual-band nanothermometers.

The hydrophobic core effect in model bacterial membranes upon interaction with tetra-p-guanidinoethylcalix[4]arene

The calixarene derivative used in this study (tetra-p-guanidinoethylcalix[4]arene) shows in vitro activity against different Gram-positive and Gram-negative bacteria. The interaction between bacterial cell membranes and the water-soluble calixarene was investigated using model lipids spread as monomolecular films at the air–water interface. Compression and adsorption experiments, as well as Brewster angle microscopy, polarization modulation-infrared reflection–absorption spectroscopy and computer modeling permitted understanding of the intra- and intermolecular interaction in several lipid-calixarene systems. Because the affinity of the calixarene derivative for the membranes may be linked to the interaction with negative charges, phosphatidylglycerols were used as model lipids; the phosphatidylglycerols contained saturated or unsaturated hydrocarbon chains with different lengths. It was showed that the affinity of the calixarene for the monolayer depends on the structure of the phosphatidylglycerols side chains. This observation may be of interest for a further development of new antibiotics.

A review on the determination heavy metals ions using calixarene-based electrochemical sensors

In aquatic environment, the presence of heavy metal in excess than permissible limits set by the World Health Organization (WHO) can cause problems to human being and aquatic life. Hence, various analytical methods have been developed to monitor the water quality by tracing different heavy metal ions in water samples. The present review summarizes the body of work (143 studies) on heavy metal determination in the past 20 years using electrochemical sensors and calixarene derivatives. The potential of calixarene derivatives to sense heavy metal ions using different electrochemical techniques were discussed. The review begins with the introduction of various electrochemical methods including potentiometry, amperometry, voltammetry and electrochemical impedance spectroscopy along with the general setup. This review provides an overview of the mechanism, main parameters of studies and application of calixarene derivatives in selective and sensitive detection. The detection of various target analytes, concentration range, and detection limit using calixarene derivative-based sensors, with different electrochemical techniques, are presented. The strengths and weaknesses of different electrochemical techniques based on calixarene derivatives are also discussed. The review shows that calixarene derivatives have great potential in sensing technology applications, specifically in heavy metal ion determination. In the end, present challenges and future prospects for translating developed sensors into portable sensing in commercial purposes is highlighted. © 2021 Elsevier Ltd. All rights reserved.

Synthesized Two New Water‐Soluble Fluorescents Calix[4]arene 4‐sulfo‐1,8‐naphthalimide Derivatives Inhibit Proliferation of Human Colorectal Carcinoma Cells

AbstractSynthesis of 1,8‐naphthalimide derivatives and biochemical studies using them as anti‐cancer and cellular imaging agents have attracted significant attention in recent years. This study aimed to synthesize two new fluorescent narrow rim‐functionalized 4‐sulfo‐1,8‐naphthalimide derivatives of calix[4]arenes (4 and 7) and examination of their cytotoxic properties for cancerous cells. For this purpose, p‐tert‐butylcalix[4]arene bearing dihydrazide (3) or diaminopropyl (6) units on its narrow rim were reacted with 4‐sulfo‐1,8‐naphthalic anhydrate. The structure of these synthesized compounds has been characterized using 1H‐NMR, 13C‐NMR, and FTIR techniques. To investigate the anti‐cancer properties, compounds 4, 7, and N,N‐dimethylaminoethyl‐1,8‐naphthalimide (8) were tested on the human colorectal cancer cell line (DLD‐1) as well as healthy colon epithelial cell line (CCD‐18Co). The IC50 values of 4 and 7 were determined as 12.95 μM and 16.13 μM, respectively, on DLD‐1 cells. Furthermore, following the treatment of CCD‐18Co cells with 4 and 7, the IC50 values were determined as 508 μM and 269 μM, respectively. However, it was observed that compound 8 had no cytotoxic effect on both DLD‐1 cells and CCD‐18Co cells. Furthermore, the fluorescence imaging of human colorectal cancer cells treated with the synthesized compounds (4, 7, and 8) was performed on living cells.

The supramolecularly complexes of calix[4]arene derivatives toward favipiravir antiviral drug (used to treatment of COVID-19): a DFT study on the geometry optimization, electronic structure and infrared spectroscopy of adsorption and sensing.

While the world is in search of a vaccine that can cure COVID-19 disease, favipiravir is the most commonly used antiviral drug in the treatment of patients during the pandemic process. In this study, we investigated the host–guest interaction between the popular supramolecule calix[4]arene derivatives and the favipiravir drug by using the DFT (Density Functional Theory) method. The B3LYP hybrid method and 6-31G (d,p) basis set were utilized to determine the optimized structures of the host and guest molecules and their complexes. The negative adsorption energy (∆E) and adsorption enthalpy (∆H) calculated for the complexes formed between calix[4]arene compounds and favipiravir drug molecule mentioned that adsorption of favipiravir molecule was an exothermic process on calix[4]arene structures. On the other hand, among the calixarene derivatives in the study, Gibbs free energy change (∆G) value for the adsorption was only negative on calix[4]arene4 molecule. The infrared spectroscopy (IR) calculations were performed by examining the C=O, O–H and NH2 vibrational frequencies to see the adsorption behavior in the favipiravir-calix[4]arene complex. After adsorption of the favipiravir molecule, HOMO–LUMO gap values decreased significantly for the structures and therefore electrical conductivity increased proportionally. In addition, sensor response factors, Fermi energy levels and workfunction changes of calix[4]arene derivatives were calculated and examined. Charge transfer between the four calix[4]arene compounds and the favipiravir molecule has occurred after adsorption. This attributes that calix[4]arene derivatives can be used as a well-suited favipiravir sensor (electronic and workfunction) and adsorbent at room temperature. Based on the calculations made to see the solvent effect on the adsorption of favipiravir it was determined that it did not affect the interaction between the drug molecule and the calix[4]arene compound too much and the adsorption energy turned into a slightly less negative value.

Supramolecular interactions in the heteroarylimine-substituted calix[4]arenes: the formation of cyclic dodecanuclear palladium aggregates

ABSTRACT Two new derivatives of calix[4]arene bearing on the upper rim 2-thiopenyl (Thicalix) or 2-pyridyl (Pycalix) Schiff-base substituents have been synthesised and characterised by IR, NMR, MS, and single crystal X-ray diffraction techniques. It was shown that the interaction of Thicalix with the copper(II) and palladium(II) ions is accompanied by hydrolysis of the azomethine bonds with subsequent oxidation of the aminophenolic fragment to diquinone Diquin, while the reaction of potassium tetrachloropalladate(II) with Pycalix results in the formation of metallocompex with 1:2 calix[4]arene/Pd(II) ratio. The single crystal X-ray diffraction analysis of Thicalix (1), the complex [(PdCl2)2(Pycalix)] (2) and Diquin (3) revealed that all compounds form molecular crystals as a result of numerous supramolecular interactions involving C − H···O, C − H···Cl, and C − H···π contacts. For 1 and 3 such interactions result in formation of dimers, while in 2 the dodecanuclear palladium aggregates composed of six calix[4]arene moieties are formed.

Review of adsorbents incorporating calixarene derivatives used for metals recovery and hazardous ions removal: the concept of adsorbent design and classification of adsorbents

Macrocyclic calixarene compounds exhibit versatile properties, which have been employed for the complexation, extraction, and transport of various metal ions. However, the potential applications of calixarenes are not straightforward. This review includes the “structural effects” of calixarene derivatives and the concept of adsorbent design incorporating calixarene derivatives after a brief introduction on the molecular design of calixarene derivatives used as extraction reagents. The adsorbents incorporating calixarene moieties are classified into four types and examples of metal adsorption using a variety of adsorbents are also introduced.

Calixarene-Embedded Nanoparticles for Interference-Free Gene-Drug Combination Cancer Therapy.

Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene-embedded nanoparticle (CENP) is developed to co-deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference-free gene-drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid-responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia-responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host-guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA-based CRISPR interference system that targets miR-21, CENP exhibits the significantly enhanced anti-tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference-free gene-drug combination cancer therapy.

Antibacterial, thermal decomposition and in vitro time release studies of chloramphenicol from novel PLA and PVA nanofiber mats

The present investigation is the first report containing design and synthesis of novel calixarene derivatives (6–8) and their inclusion complexes (IC6–IC8) with Chloramphenicol (CAM). After synthesis, the antibiotic CAM, calixarene derivatives (6–8) and their inclusion complexes (IC6–IC8) were successfully incorporated into biodegradable PVA and/or PLA nanofiber skeleton by electrospinning. The obtained electrospun nanofibers were tested and compared for inhibition of bacterial growth towards multiple bacterial species (Escherichia coli, and Bacillus subtilis). Moreover, we evaluated thermal decomposition and release profile of CAM by spectrophotometric methods. The results suggested that CAM can be successfully encapsulated in nanofiber webs by inclusion complexation, and these fibers could be used as a part of new controlled release packaging system for food preservation.