calixarenes and resorcinarene

We review here the use of container molecules known as cavitands for performing organic reactions in water. Central to these endeavors are binding forces found in water, and among the strongest of these is the hydrophobic effect. We describe how the hydrophobic effect can be used to drive organic molecule guests into the confined space of cavitand hosts. Other forces participating in guest binding include cation-π interactions, chalcogen bonding and even hydrogen bonding to water involved in the host structure. The reactions of guests take advantage of their contortions in the limited space of the cavitands which enhance macrocyclic and site-selective processes. The cavitands are applied to the removal of organic pollutants from water and to the separation of isomeric guests. Progress is described on maneuvering the containers from stoichiometric participation to roles as catalysts.

Topics: Calixarenes; Ethers, Cyclic; Models, Molecular; Phenylalanine; Resorcinols; Water

Calixarenes and related macrocycles have been shown to have antimicrobial effects since the 1950s. This review highlights the antimicrobial properties of almost 200 calixarenes, resorcinarenes, and pillararenes acting as prodrugs, drug delivery agents, and inhibitors of biofilm formation. A particularly important development in recent years has been the use of macrocycles with substituents terminating in sugars as biofilm inhibitors through their interactions with lectins. Although many examples exist where calixarenes encapsulate, or incorporate, antimicrobial drugs, one of the main factors to emerge is the ability of functionalized macrocycles to engage in multivalent interactions with proteins, and thus inhibit cellular aggregation.

Topics: Amino Acid Motifs; Animals; Anti-Infective Agents; Biofilms; Calixarenes; Drug Delivery Systems; Glycosylation; Humans; Lectins; Metals; Nanoparticles; Oxazoles; Phenylalanine; Prodrugs; Solubility; Sulfonamides; Thiadiazoles; Thiazoles; Vancomycin; Water

Post-translational modifications (PTMs) describe the chemical alteration of proteins after their biosynthesis in ribosomes. PTMs play important roles in cell biology, including the regulation of gene expression, cell-cell interactions and the development of different diseases. A prominent class of PTMs is the side-chain methylation of lysine. For the analysis and discrimination of differently methylated lysines, antibodies are widely used, although methylated peptide and protein targets are known to be particularly difficult to differentiate by antibody-based affinity reagents; an additional challenge can be batch-to-batch reproducibility. The application of mass spectrometry techniques for methyllysine discrimination requires a complex sample preparation procedure and is not suited for working in cells. The desire to overcome the above-mentioned challenges has promoted the development of synthetic receptor molecules that recognise and bind methyllysines. Such "artificial antibodies" are of interest for a number of applications, for example, as reagents in biochemical assays, for the isolation and purification of post-translationally methylated proteins and for the tracking of signalling pathways. Moreover, they offer new approaches in diagnostics and therapy. This review delivers an overview of the broad field of methyllysine binding and covers a wide range of synthetic receptors used for the recognition of methylated lysines, including calixarenes, resorcinarenes, pillararenes, disulfide cyclophanes, cucurbiturils and acyclic receptors.

Topics: Antibodies; Calixarenes; Lysine; Macrocyclic Compounds; Methylation; Phenylalanine; Protein Binding; Protein Processing, Post-Translational; Proteins; Receptors, Artificial; Reproducibility of Results

A short introduction to the fundamental features and recent developments of supramolecular chemistry is presented besides defining scope and limitation of this review article. A brief overview about calix[n]arenes and especially resorcin[4]arenes and their conformationally rigid cavitands is given. Selected examples are presented to demonstrate the dependence of self-assembly of cavitands exhibiting different flexibility either due to their basic macrocycle or due to flexible receptor units commonly located at the o,o'-position of the resorcinarene ring. In addition, the process of self-assembly is also controlled by metal coordination geometry as shown by one example. The receptor units may also be connected at the methylene group of the cavitand as shown by one example. Examples of supramolecular architectures are presented utilizing the special features of 2,2':6',2″-terpyridine (terpy) metal-binding ligand. The synthesis and characterization of a metallo-supramolecular Zn-coordination cage with a diameter of 4-5 nm based on a cavitand-terpy building block is presented in detail.

Topics: Calixarenes; Ethers, Cyclic; Models, Molecular; Molecular Structure; Organometallic Compounds; Phenylalanine; Pyridines; Resorcinols

Noncovalent diastereomeric ion-molecule complexes are produced in the gas phase and are ideal for the study of chiral recognition in the absence of complicating solvent and counterion effects. This review article describes the state-of-art in this field with special emphasis on the most recent mass spectrometric studies of the structure, dynamics, and reactivity of diastereomeric ion/molecule aggregates.

Topics: Amides; beta-Cyclodextrins; Calixarenes; Gases; Phenylalanine; Stereoisomerism; Substrate Specificity

The design of phosphorus-containing cavity architectures that are of interest for biomimetics and other interdisciplinary sciences is among the most high-priority lines of research in modern organophosphorus chemistry. This Account acquaints the readers with methods for the design of rigid phosphomacrocyclic systems based on resorcinarenes, which differ in the nature of the phosphorus functions on the upper rim of the molecular bowl and have fixed dimensions of the molecular cavity. The authors demonstrate the possibility of attaining stereoselectivity in the synthesis of phospho(III)cavitands and their various transformations.

Topics: Calixarenes; Cyclization; Ethers, Cyclic; Molecular Structure; Organophosphorus Compounds; Phenylalanine; Phosphorylation; Resorcinols

Container-shaped molecules provide structured environments that impart geometric bounds on the motions and conformations of smaller molecular occupants. Moreover, they provide "solvation" that is constrained in time and space. When inwardly directed functional groups are present, they can interact chemically with the occupants. Additionally, the potential for reactivity and catalysis is greatly enhanced. Deep cavitands, derived from resorcinarenes, nearly surround smaller molecules and have been one of the most successful platforms for elaboration with functional groups. Derivatives bearing organic and metal-binding functional groups have been shown to affect recognition properties and selectively accelerate diverse reactions. In this review, we examine recent examples of these systems with an emphasis on how and why ordered nanoenvironments impart changes in the properties and reactivity of their occupants.

Topics: Binding Sites; Calixarenes; Drug Design; Models, Molecular; Molecular Conformation; Molecular Structure; Nanotechnology; Phenylalanine; Thermodynamics

Kynurenic acid is a by-product of tryptophan metabolism in humans, with abnormal levels indicative of disease. There is a need for water-soluble receptors that selectively bind kynurenic acid, allowing for detection and quantification. We report here the high-affinity binding of kynurenic acid in aqueous media to a resorcinarene salt receptor decorated with four flexible naphthalene groups at the upper rim. Experimental results from

Topics: Calixarenes; Humans; Kynurenic Acid; Naphthalenes; Phenylalanine; Tryptophan; Water

The hexameric undecyl-resorcin[4]arene capsule (

Topics: Calixarenes; Phenylalanine

The synthesis of phenyl-resorcinarenes and pyrogallolarenes is known to produce a conformational mixture of cone and chair isomers. Depending on the synthesis conditions the composition of the conformational mixture is variable; however, the cone conformer is the greatest proportion of phenyl-resorcin[4]arenes and chair conformer of pyrogallol[4]arenes. The experimental evidence suggests that phenyl-substituted resorcinarene and pyrogallolarene exist as a dynamic boat in solution.

Topics: Calixarenes; Magnetic Resonance Spectroscopy; Models, Molecular; Phenylalanine; Pyrogallol

The first example of conjugation of open-resorcinarenes with chlorambucil, ibuprofen, naproxen and indomethacin are presented. The cytotoxic properties of the obtained conjugates were tested against the cancer cell lines U-251, PC-3, K-562, HCT-15, MCF-7 and SKLU-1. It was found that the conjugate with chlorambucil, naproxen or indomethacin (having 8 moieties) was toxic towards cancer cell lines U-251 and K-562, with no activity against non-cancerous COS-7 cells. The conjugates with naproxen and indomethacin showed high selectivity towards U-251 tumor cells.

Topics: Animals; Antineoplastic Agents; Calixarenes; Cell Line, Tumor; Cell Proliferation; Chlorocebus aethiops; COS Cells; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Phenylalanine; Structure-Activity Relationship

Disinfection byproducts such as trihalomethanes are commonly found in drinking water. Trihalomethanes are formed upon chlorination of natural organic matter found in many drinking water sources. Inspired by molecular CHCl

Topics: Adsorption; Calixarenes; Dioxanes; Drinking Water; Phenylalanine; Polymers; Porosity; Trihalomethanes; Water Pollutants, Chemical; Water Purification

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 (>5 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 5 mM glucose, the nanocarrier is stable, and the insulin release does not exceed 10 %. Increasing the glucose concentration to 7.5-10 mM results in a 40-100 % insulin release. p(6SRA-5B) is thus a promising insulin nanocarrier for the treatment of type 1 diabetes.

Topics: Boronic Acids; Calixarenes; Diabetes Mellitus, Type 1; Drug Carriers; Drug Delivery Systems; Drug Liberation; Glucose; Humans; Insulin; Phenylalanine; Polymers; Sulfonic Acids

A possible way of improving the activity and selectivity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules. Thus, four resorcinarene-PAMAM-dendrimer conjugates of chlorambucil with different groups in the lower part of the macrocycle and different length dendritic arms showed a good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the resorcinarene-PAMAM-dendrimer-chlorambucil conjugate employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) demonstrated that the conjugate was more potent as an antiproliferative agent than chlorambucil.

Topics: Antineoplastic Agents; Calixarenes; Chlorambucil; Dendrimers; Drug Carriers; Drug Screening Assays, Antitumor; Humans; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Phenylalanine

Two calix[4]resorcinarenes, which differ in the length of the alkyl chain on the methylene bridge between the aromatic rings, have been embedded in unilamellar liposomes prepared from 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine in three host/guest ratios, following two different procedures. The effect of the insertion of the guests has been evaluated through the measurements of the viscosity and the kinetic stability of the liposomal systems by means of the fluorescent probes pyrene and 5(6)-carboxyfluorescein. The presence of the guests reduces the viscosity of the liposomes, suggesting a modification of the bilayer structure. However, this does not affect liposome stability. A calix[4]resorcinarene cavitand with a more rigid conformation compared to the parent resorcinarene, has been also synthetized and embedded in liposomes. The free energy of the insertion of the substrates in the lipid bilayer has been evaluated through Molecular Dynamics simulations.

Topics: Calixarenes; Kinetics; Lipid Bilayers; Liposomes; Molecular Dynamics Simulation; Phenols; Phenylalanine; Viscosity

A new supramolecular system based on halogen-bonded macromolecular substances is presented. Binding and complex formation between a halogen bond acceptor N-benzyl ammonium resorcinarene bromide and a library of polymeric halogen bond donors based on iodotetrafluorophenoxy functionality is shown. The complex formation was confirmed in liquid state by dynamic light scattering and transmission electron microscopy. Spectroscopic measurements in the solid state verify the halogen bonding. In particular, the study shows that both homopolymers and polyethylene glycol block copolymers act as effective halogen bond donors leading to polymer-architecture-dependent complex morphologies.

Topics: Calixarenes; Halogens; Macromolecular Substances; Magnetic Resonance Spectroscopy; Molecular Structure; Phenylalanine; Polymers

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

Topics: Anti-Bacterial Agents; Calixarenes; Cell Death; Diffusion; Electric Conductivity; Humans; Macrocyclic Compounds; Particle Size; Phenylalanine; Static Electricity; Surface Tension

Resorcinarenes are macrocyclic molecules that can bind different molecules in a supramolecular fashion. There are some sulfonated water-soluble derivatives that have been investigated to bind proteins avoiding fibrillation. The interaction with enzymes such as catalase (CAT) allows the interpretation of the possible effects of the use of resorcinarenes on human health or environmental applications. The interaction of five sulfonated resorcinarenes with different chemical structures was investigated by using different biophysical methods. The results of the spectroscopic experiments (fluorescence, synchronous fluorescence, and Uv-vis spectrophotometry) show different degrees of structural change, indicating that the binding of the macrocycles that were studied causes alterations on the conformation of CAT. The resorcinarenes reduce the activity of CAT in different extent, two macrocycles (named Na

Topics: Animals; Calixarenes; Catalase; Cattle; Liver; Molecular Docking Simulation; Phenylalanine; Protein Binding; Protein Conformation; Solubility; Sulfonic Acids; Water

The synthesis of conjugates of flutamide with resorcinarene-PAMAM-dendrimers as well as alkyl and ethyl phenyl chains in the lower part of the macrocycle as a nucleus and diethylenetriamines in the dendritic branches gives the opportunity to obtain conjugates in one step of synthesis with 16 and 64 flutamide moieties in the structure.. The in vitro anticancer studies showed that the conjugates of flutamide are more active than the free flutamide and the flutamide derivatives, thus diminishing the amount of flutamide used. The resorcinarenedendrimer- flutamide conjugates with a high drug payload improve the activity of the drug.. This is important in delivering a sufficient amount of flutamide and suggests that the dendrimer facilitates more of the drug being introduced into cells. It was also observed that the new conjugates are less toxic than the anti-androgens.

Topics: Antineoplastic Agents; Apoptosis; Calixarenes; Cell Line, Tumor; Cell Proliferation; Dendrimers; Drug Carriers; Flutamide; Humans; Models, Molecular; Neoplasms; Phenylalanine

The thermodynamics of the retention mechanism of resorcinarene-based cavitands in RPLC as well as the nature of the binding sites have been studied recently. In the present study, the influence of pressure on the retention of the cyclic tetramers on alkylsilyl and polar-embedded C

Topics: Calixarenes; Chemistry Techniques, Analytical; Chromatography, Liquid; Ethers, Cyclic; Methanol; Phenylalanine; Pressure; Resorcinols; Silicon Dioxide; Thermodynamics; Water

Substituted 2,4- and 4,6-dihydroxyisophthalaldehydes were condensed with optically pure and racemic trans-1,2-diaminocyclohexane to form resorcinarene-like polyimine macrocycles (resorcinsalens), the structure and stoichiometry of which were controlled by the choice of the reaction medium. Particularly, the cyclocondensation reactions were driven by the solubility, tautomerization, or by social self-sorting. The resorcinsalens crystallized as inclusion compounds, in which the guest molecules were situated either in channels or in voids. In the highly hydrated crystals of one of the [2+2] macrocycles and chloroform-solvated crystals of a [4+4] product the channels were interconnected, as in zeolites, enabling possible migration of loosely bound solvent molecules in three dimensions. The association mode depended on the structural modification of the host molecule and the type of included solvent molecule(s).

Topics: Calixarenes; Cyclohexylamines; Models, Molecular; Molecular Structure; Phenylalanine; Phthalic Acids; Solvents; Stereoisomerism

Plant phenolic compounds and catecholamines have been widely used to obtain substrate-independent precursor nanocoatings and adhesives. Nevertheless, there are downsides in using such phenolic compounds for surface modification such as formation of nonuniform coatings, need for multistep modification, and restricted possibilities for postfunctionalization. In this study, inspired by a strong binding ability of natural polyphenols found in plants, we used three different macrocyclic polyphenols, known as resorcin[4]arenes, to modify the surface of different substrates by simple dip-coating into the dilute solution of these compounds. Eight hydroxyl groups on the large rim of these resorcin[4]arenes provide multiple anchoring points to the surface, whereas the lower rim decorated with different appending groups introduces the desired chemical and physical functionalities to the substrate's surface. Deposition of a uniform and transparent resorcinarene layer on the surface was confirmed by several surface characterization techniques. Incubation of the modified substrates in different environments indicated that the stability of the resorcinarene layer was dependent on the type of substrate and the pH value. The most stable resorcinarene layer was formed on amine-functionalized substrates. The surface was modified with alkenyl functional groups in one step using a resorcinarene compound possessing four alkenyl appending groups on its small rim. Thiol-ene photoclick chemistry was used to site-selectively postfunctionalize the surface with hydrophilic and hydrophobic micropatterns, which was confirmed by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Thus, we demonstrate that resorcin[4]arenes extend the scope of applications of plant polyphenol and mussel-inspired precursors to tailor-made multifunctional nanocoatings, suitable for a variety of potential applications in biotechnology, biology, and material science.

Topics: Biomimetic Materials; Calixarenes; Phenylalanine; Photochemistry; Surface Properties; Wettability

Two synthetic protocols for the introduction of fluorine atoms into resorcinarene-based cavitands, at the lower and upper rim, respectively, are reported. Cavitand

Topics: Calixarenes; Cations; Ethers, Cyclic; Fluorine; Halogenation; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Structure; Organophosphonates; Phenylalanine; Resorcinols; Sarcosine

The tail-to-head terpene cyclization is arguably one of the most complex reactions found in nature. The hydrogen-bond-based resorcinarene capsule represents the first man-made enzyme-like catalyst that is capable of catalyzing this reaction. Based on noncovalent interactions between the capsule and the substrate, the product selectivity can be tuned by using different leaving groups. A detailed mechanistic investigation was performed to elucidate the reaction mechanism. For the cyclization of geranyl acetate, it was found that the cleavage of the leaving group is the rate-determining step. Furthermore, the studies revealed that trace amounts of acid are required as cocatalyst. A series of control experiments demonstrate that a synergistic interplay between the supramolecular capsule and the acid traces is required for catalytic activity.

Topics: Acetates; Acyclic Monoterpenes; Calixarenes; Catalysis; Cyclization; Hydrogen Bonding; Models, Molecular; Phenylalanine; Terpenes

Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were carried out with pure conformers, and it was observed that the reaction between tetra(4-hydroxyphenyl)calix[4]resorcinarene fixed in the chair conformation does not occur, while for the molecule fixed in the crown conformation only one tetraalkylated derivative was obtained. The obtained product was characterized using IR, ¹H-NMR,

Topics: Alkylation; Calixarenes; Crown Ethers; Phenylalanine

Different tail-engineered resorcinarenes have been examined for insulin fibrillation by experimental and computational studies. The resorcinarene showed a promising effect on the inhibition of insulin fibrillation, studied using a ThT assay, circular dichroism spectroscopy, and atomic force microscopy. Both the ThT assay and computational results indicate the tail from the resorcinarene has an impact on insulin fibrillation by either inhibition or promotion because of the resident position on insulin. These observations have significant biological implications in the design of drug molecules as well as the development of potential therapeutic strategies.

Topics: Calixarenes; Circular Dichroism; Dynamic Light Scattering; Humans; Insulin; Kinetics; Microscopy, Atomic Force; Molecular Dynamics Simulation; Phenylalanine; Spectrometry, Fluorescence; Water

Efficient enantiodiscrimination of some alanine-containing di- and tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide.

Topics: Alanine; Calixarenes; Diamide; Kinetics; Molecular Conformation; Peptides; Phenylalanine; Protons; Quantum Theory; Stereoisomerism

As a membrane-mimetic system, detergent micelles are popularly used to extract membrane proteins from lipid environments and to maintain their solubility and stability in an aqueous medium. However, many membrane proteins encapsulated in conventional detergents tend to undergo structural degradation during extraction and purification, thus necessitating the development of new agents with enhanced properties. In the current study, two classes of new amphiphiles are introduced, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), for which the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional detergent. The relatively high water solubility and micellar stability of the RGAs compared to the RMAs, along with their generally favourable behaviours for membrane protein stabilisation described here, are likely to be, at least in part, a result of the high conformational flexibility of these glucosides. This study suggests that flexibility could be an important factor in determining the suitability of new detergents for membrane protein studies.

Topics: Aspergillus nidulans; Bacterial Proteins; Calixarenes; Coumarins; Detergents; Fungal Proteins; Glycosides; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Membrane Transport Proteins; Phenylalanine; Protein Denaturation; Protein Stability; Salmonella typhimurium; Symporters

Trace levels of pharmaceuticals have been detected in surface water and may pose a health risk to humans and other organisms. New chromatographic materials will help identify and quantify these contaminants. We introduce a new ion chromatographic (IC) material designed to separate cationic pharmaceuticals and report its ability to separate a group of guanidine compounds. Guanidine moieties are strongly basic and protonated under acid conditions, and therefore can potentially be separated on the newly designed stationary phase and detected by ion exchange chromatography. The new column packing material is based on glutamic acids bonded to resorcinarene moieties that in turn are bound to divinylbenzene macroporous resin. Detection limits in the range of 5-30 μg L(-1) were achieved using integrated pulsed amperometric detection (IPAD) for guanidine (G), methylguanidine (MG), 1,1-dimethylbiguanide (DMG), agmatine (AGM), guanidinobenzoic acid (GBA) and cimetidine (CIM). Suppressed conductivity (CD) and UV-vis detection resulted in limits of detection similar to IPAD, in the range of 2-66 μg L(-1), but were not able to detect all of the analytes. Three water sources, river, lake, and marsh, were analyzed and despite matrix effects, sensitivity for guanidine compounds was in the 100 μg L(-1) range and apparent recoveries were 80-96%. The peak area precision was 0.01-2.89% for IPAD, CD and UV-vis detection.

Topics: Calixarenes; Chromatography, Ion Exchange; Glutamic Acid; Guanidine; Lakes; Limit of Detection; Mesylates; Phenylalanine; Reproducibility of Results; Rivers; Water; Water Pollutants, Chemical

The synthesis of N-benzyl- and N-cyclohexylammonium resorcinarene trifluoroacetate (TFA) and triflate (OTf) salt receptors was investigated. Solid-state analysis by single-crystal X-ray diffraction revealed that the N-alkylammonium resorcinarene salts (NARSs) with different upper substituents had different cavity sizes and different affinities for anions. Anion-exchange experiments by mixing equimolar amounts of N-benzylammonium resorcinarene trifluoroacetate and N-cyclohexylammonium resorcinarene triflate, as well as N-benzylammonium resorcinarene triflate and N-cyclohexylammonium resorcinarene trifluoroacetate showed that the NARS with flexible benzyl groups preferred the larger OTf anion, whereas the rigid cyclohexyl groups preferred the smaller TFA anions. The anion-exchange processes were confirmed in the solid state by single-crystal and powder X-ray diffraction experiments and in the gas phase by electrospray ionization mass spectrometry.

Topics: Anions; Benzylammonium Compounds; Calixarenes; Crystallography, X-Ray; Dioxanes; Mesylates; Models, Molecular; Phenylalanine; Salts; Trifluoroacetic Acid

Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen-bond-based self-assembly. The dynamic character of the linkers and the preference of the peptides towards self-assembly into β-barrel-type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 Å(3) and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self-sorting and chiral self-assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70 , is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70 , and the X-ray structures provide unique information on the modes of peptide-fullerene interactions.

Topics: Calixarenes; Fullerenes; Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Peptides; Phenylalanine; Stereoisomerism

The synthesis of novel spatially directional multivalent resorcin[4]arene cavitand glycoconjugates (RCGs) and their ability to catalyze organic reactions is reported. The β-d-glucopyranoside moieties on the upper rim of the "bowl"-shaped resorcin[4]arene cavitand core are capable of multiple hydrogen-bond interactions resulting in a pseudo-cavity, which has been investigated for organic transformations in aqueous media. The RCGs have been demonstrated to catalyze thiazole formation, thiocyanation, copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), and Mannich reactions; they impart stereoselectivity in the three-component Mannich reaction. Thermodynamic values obtained from (1) H diffusion-ordered spectroscopy (DOSY) experiments suggest that the upper saccharide cavity of the RCG and not the resorcin[4]arene cavity is the site of the complexation event.

Topics: Alkynes; Azides; Calixarenes; Catalysis; Copper; Cycloaddition Reaction; Glycoconjugates; Phenylalanine; Thermodynamics

Cavitands are cavity-shaped cyclic oligomers and they can create host-guest interactions with various analytes, therefore they have applications in supramolecular chemistry, nanoscale reactions, chromatographic separations, drug encapsulation and delivery, biochemistry. The investigation of the chromatographic behavior of large molecules, such as resorcinarenes and cavitands is meager up to now. To understand the retention of resorcinarenes and cavitands in liquid chromatography, we studied their retention mechanism by the thermodynamic parameters calculated from the van't Hoff equation and by generation of an adsorption isotherm, which can describe the adsorption of the solute on the stationary phase surface. We compared the thermodynamics of the retention for cyclic oligomers in acetonitrile:water and methanol:water mobile phases. Furthermore, we determined the equilibrium adsorption isotherm by inverse method and we made an error analysis of the estimation obtained with the inverse method to ascertain the validity of the obtained isotherm parameters over a broader concentration range.

Topics: Acetonitriles; Adsorption; Algorithms; Calixarenes; Chromatography, Liquid; Ethers, Cyclic; Methanol; Phenylalanine; Resorcinols; Solvents; Thermodynamics; Water

A key challenge in chemical biology is to identify small molecule regulators for every single protein. However, protein surfaces are notoriously difficult to recognise with synthetic molecules, often having large flat surfaces that are poorly matched to traditional small molecules. In the surface mimetic approach, a supramolecular scaffold is used to project recognition groups in such a manner as to make multivalent non-covalent contacts over a large area of protein surface. Metal based supramolecular scaffolds offer unique advantages over conventional organic molecules for protein binding, including greater stereochemical and geometrical diversity conferred through the metal centre and the potential for direct assessment of binding properties and even visualisation in cells without recourse to further functionalisation. This feature article will highlight the current state of the art in protein surface recognition using metal complexes as surface mimetics.

Topics: Animals; Biomimetics; Calixarenes; Coordination Complexes; Dendrimers; Humans; Models, Molecular; Phenylalanine; Porphyrins; Protein Binding; Proteins

Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 10(9) M(-1) cm(-1) and 1.5 × 10(8) M(-1) cm(-1) respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

Topics: Animals; Calixarenes; Ethers, Cyclic; Mice; Nanocapsules; Phenylalanine; Resorcinols; Tissue Distribution

Self-assembled resorcin[4]arene hexamer catalyzes the intramolecular hydroalkoxylation of unsaturated alcohols to the corresponding cyclic ethers under mild conditions. The mode of catalysis and encapsulation-based substrate selectivity of the host efficiently mimic the basic principle of operation observed in enzymes.

Topics: Alcohols; Alkenes; Biomimetic Materials; Calixarenes; Catalysis; Enzymes; Phenylalanine; Polymerization; Substrate Specificity

Encapsulation of a cationic carbodiimide condensing agent within a self-assembled hexameric capsule made of resorcin[4]arene units provides a nano-environment that efficiently steers the substrate selectivity in the amide synthesis reaction between carboxylic acids and primary amines. While in solution pairs of acids react similarly with a given amine, in the presence of the capsule the formation of the shorter amide is greatly favored.

Topics: Amides; Calixarenes; Capsules; Carbodiimides; Models, Molecular; Phenylalanine; Substrate Specificity

People with chronic kidney disease suffer from uremic toxins which accumulate in their bodies. Detection and quantification of uremic toxins help diagnose kidney problems and start patient care. The aim of this research was to seek a new method to assist this diagnosis by trace level detection and separation of guanidine containing uremic toxins in water and urine. To detect and quantify the uremic toxins, new stationary phases for ion chromatography (IC) columns based on glutamic acid functionalized resorcinarenes bound to divinylbenzene macroporous resin were prepared. The new column packing material afforded separation of the five compounds: guanidinoacetic acid, guanidine, methylguanidine, creatinine, and guanidinobenzoic acid in 30min. Peak resolutions ranged from 7.6 to 1.3. Gradient elutions at ambient temperature with methanesulfonic acid (MSA) solution as eluent resulted in detection levels in water from 10 to 47ppb and in synthetic urine from 28 to 180ppb. Limits of quantification for the analytes using pulsed amperometric detection were 30-160ppb in water and 93-590ppb in urine. Trace levels of creatinine (1ppm) were detected in the urine of a healthy individual using the columns.

Topics: Calixarenes; Chromatography, Ion Exchange; Creatinine; Glutamic Acid; Guanidines; Humans; Indicators and Reagents; Phenylalanine; Water

Two sulfonated resorcinarenes were synthesized by reacting C-tetra(butyl) resorcinarene or C-tetra(2-(methylthio)ethyl)resorcinarene with formaldehyde in the presence of sodium sulfite. Their structures were determined via FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. Thermal gravimetric analyses of the derivatives were also carried out and revealed the presence of water molecules in the solid state. The sulfonated product of C-tetra(butyl)resorcinarene was characterized by an X-ray crystal structure determination. The asymmetric unit contains eight molecules of water and two of acetone, and analysis indicated that sulfonated resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the crystal array, classical hydrogen bond interactions O-H···O and intermolecular contacts were observed. In the crystal packing, a linear array of capsules of sulfonated resorcinarenes was generated for a chain of sodium atoms and sulfonate groups.

Topics: Acetone; Alkanesulfonates; Calixarenes; Crystallography, X-Ray; Formaldehyde; Hydrogen Bonding; Molecular Conformation; Phenylalanine; Solubility; Sulfites; Water

The understanding of the retention behavior of large molecules is an area of interest in liquid chromatography. Resorcinarene-based cavitands are cavity-shaped cyclic oligomers that can create host-guest interactions. We have investigated the chromatographic behavior of two types of cyclic tetramers as analytes in high-performance liquid chromatography. The experiments were performed at four different temperatures (15, 25, 35, 45°C) on two types of reversed stationary phases (C8 and C18 ) from two different manufacturers. We have found a huge difference between the retention of resorcinarenes and cavitands. In some cases, the retention factor of cavitands was even a hundred times larger than the retention factor of resorcinarenes. The retention of methylated derivates was two to four times larger compared to that of demethylated compounds on every column. The opposite retention behavior of the resorcinarenes and cavitands on the two types of stationary phases showed well the difference of the selectivity of the XTerra and BDS Hypersil columns. The retention mechanism was studied by the thermodynamic parameters calculated from the van't Hoff equation.

Topics: Calixarenes; Chromatography, High Pressure Liquid; Chromatography, Liquid; Ethers, Cyclic; Phenylalanine; Resorcinols; Temperature; Thermodynamics

An unexpected and previously unknown resorcinarene mono-crown with a fused benzofuran moiety in its macrocyclic core was obtained as a byproduct from a bridging reaction of tetramethoxy resorcinarene with tetraethylene glycol ditosylate. The formation of the fused benzofuran moiety in the resorcinarene macrocycle resulted in a unique rigid and puckered boat conformation, as shown by XRD studies in the solid state. Modification of the macrocycle was also observed to affect the photophysical properties in solution by enhancing the fluorescence brightness compared with a conventional resorcinarene macrocycle. The fluorescent properties enabled unique detection of structural features, that is, the rigid boat conformation with the conjugated benzofuran system and the more flexible crown bridge part, in solution.

Topics: Benzofurans; Calixarenes; Chemistry Techniques, Synthetic; Crystallography, X-Ray; Fluorescence; Molecular Conformation; Molecular Structure; Phenylalanine; Spectrometry, Fluorescence; Structure-Activity Relationship

A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this particular derivative has an efficient antioxidant activity and a negligible cytotoxic effect, making it a potential target for further biological investigations.

Topics: Animals; Antioxidants; Benzaldehydes; Calixarenes; Humans; Phenylalanine; Plant Extracts; Toxoplasma; Toxoplasmosis

We report the synthesis, structural characterization, and binding properties of a series of unprecedented cavitands based on a meso-dodecyl-calix[4]pyrrole-resorcin[4]arene hybrid scaffold. The reported structural and conformational features of the prepared cavitands are derived from results obtained in solution, solid state, and molecular modeling studies. In the solid state, these cavitands are exclusively observed in the kite C4 structure and as a racemic mixture of two cyclochiral conformers, which are interconverting fast on the (1)H NMR time scale, according to solution studies. In agreement, molecular modeling studies assign an energy preference for the kite conformer of the cavitands. The polar interior of the synthesized containers allows for the inclusion of a series of pyridine N-oxide derivatives. This results in the formation of 1:1 complexes that are kinetically and thermodynamically highly stable. The putative switching process between the vase and kite forms of these cavitands is investigated in solution by means of variable temperature (1)H NMR experiments. N-Oxide guests that are size and shape complementary to the volume of the cavity of the vase form are also employed to facilitate its emergence. All of the results obtained indicate the existence of a remarkable preference toward the kite conformation both in free and bound calix[4]pyrrole-based cavitands.

Topics: Calixarenes; Ethers, Cyclic; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Phenylalanine; Pyridines; Resorcinols

Modeling the mononuclear site of copper enzymes is important for a better understanding of the factors controlling the reactivity of the metal center. A major difficulty stems from the difficult control of the nuclearity while maintaining free sites open to coordination of exogenous ligands. A supramolecular approach consists in associating a hydrophobic cavity to a tripodal ligand that will define the coordination spheres as well as access to the metal ion. Here, we describe the synthesis of a bowl Cu(II) complex based on the resorcinarene scaffold. This study supplements a previous work on Cu(I) coordination. It provides a complete picture of the cavity-copper system in its two oxidation states. The first XRD structure of such a bowl complex was obtained, evidencing a 5-coordinate Cu(II) ion with the three imidazole donors bound to the metal (two in the base of the pyramid, one in the apical position) and with an acetate anion, completing the base of the pyramid, and deeply included in the bowl. Solution studies conducted by EPR and UV-vis absorption spectroscopies as well as cyclic voltammetry highlighted interaction with coordinating solvents, various carboxylates that can sit either in the endo or in the exo position depending on their size as well as possible stabilization of hydroxo species in a mononuclear state. A comparison of the binding and redox properties of the bowl complex with funnel complexes based on the calix[6]arene core further highlights the importance of supramolecular features defining the first, second, and third coordination sphere for control of the metal ion.

Topics: Biocatalysis; Biomimetics; Calixarenes; Coordination Complexes; Copper; Crystallography, X-Ray; Models, Molecular; Oxidation-Reduction; Phenols; Phenylalanine

Topics: Calixarenes; Catalysis; Ethanol; Furans; Hydrochloric Acid; Phenylalanine; Reproducibility of Results; Resorcinols; Water

The conformation of resorcin[4]arene cavitand system 1 was controlled by DMSO through a hydrogen bonding network between benzodiazaborole NHs of the cavitand flaps and DMSO molecules to stabilize the vase form. Subsequently, a guest-binding cavity of 1 was formed to accommodate tetraalkylammonium guest 3, permitting the monitoring of the guest by the unaided eye as a result of a CH-π interaction between the benzodiazaborole π-donor group and the guest.

Topics: Aza Compounds; Boron Compounds; Calixarenes; Fluorescence; Hydrogen Bonding; Molecular Structure; Phenylalanine; Solvents

The recently dramatic increase in the available choices of reversed-phase columns could be an advantage of this mode of separation. However, due to the insufficiency of available information in terms of the exact functionality of these phases and the similarities and differences between these newly introduced and conventional reversed-phase columns, it is now somehow problematic to determine which could be the best column for a given analytical problem. There is no single column that will give us a good separation for all applications. As a result, there have been several attempts to develop testing strategies to characterize column chemistries. In this study three of the most widely used and acceptable approaches for the characterization of reversed-phase columns, which are Tanaka, United States Pharmacopeia (USP), and Snyder-Dolan, are systemically applied to investigate the chromatographic properties of calixarene- and resorcinarene-bonded stationary phases, polar-embedded and polar-endcapped stationary phases, phenyl and ether-linked phenyl with the presence of conventional alkyl-bonded phases (octyl- and octadecylsilane). Although all column classification systems aim to evaluate "more or less" the same characteristics, each system uses different test mixtures in different chromatographic conditions. It is therefore very important to evaluate the similarities and differences in the resulted "column parameters" and the possible interchangeability of them. The results of this comparative study show that the used parameters of Tanaka and of Snyder-Dolan have in many cases a good to very good correlation. The USP approach, which is based on single run, is related to Tanaka and Snyder-Dolan only in terms of hydrophobic characters, and no relation could establish in the other parameters. The hydrophobic-subtraction model could be extended to describe the ligand-solute interactions of calixarene- and resorcinarene-bonded stationary phases, which are belonging to reversed phase material. However they show, depending on the analytes, some additional interactions, since their steric, polar and ionic properties are different compared to those of conventional alkyl-bonded phases.

Topics: Calixarenes; Chromatography, High Pressure Liquid; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Models, Theoretical; Phenylalanine

The facile synthesis of a resorcin[4]arene-based imino-cavitand with benzamido moieties and its self-assembly into molecular capsules are reported. Benzamido-iminocavitand efficiently self-assembled into thermally inert molecular capsules in the presence of suitable guests via the eight intermolecular N-H···O=C hydrogen bonds.

Topics: Benzamides; Calixarenes; Ethers, Cyclic; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Conformation; Phenylalanine

Resorc[4]arenes 1 and 2, which previously proved to entrap NO(+) cation within their cavities under conditions of host-to-guest excess, were treated with a 10-fold excess of NOBF4 salt in chloroform. Kinetic and spectral UV-visible analyses revealed the formation of isomeric 1:2 complexes as a direct evolution of the previously observed event. Accordingly, three-body 1-(NO(+))2 and 2-(NO(+))2 adducts were built by MM and fully optimized by DFT calculations at the B3LYP/6-31G(d) level of theory. Notably, covalent nitration products 4, 5 and 6, 7 were obtained by reaction of NOBF4 salt with host 1 and 2, respectively, involving macrocycle ring-opening and insertion of a nitro group in one of the four aromatic rings. In particular, compounds 4 and 6, both containing a trans-double bond in the place of the methine bridge, were oxidized to aldehydes 5 and 7, respectively, after addition of water to the reaction mixture. Calculation of the charge and frontier orbitals of the aromatic donor (HOMO) and the NO(+) acceptor (LUMO) clearly suggests an ipso electrophilic attack by a first NO(+) unit on the resorcinol ring, mediated by the second NO(+) unit.

Topics: Calixarenes; Cations; Macromolecular Substances; Molecular Structure; Nitric Oxide; Phenylalanine; Quantum Theory

Bis(diamido)-bridged basket resorcin[4]arene (all-S)-1 and its (all-R)-1 enantiomer proved able to interact with 2'-deoxycytidine (2) and pyrimidine nucleoside analogs in dimethyl sulfoxide (DMSO) solution. In such a solvent, the resorcinarene hosts adopt a preferential 1,3-alternate-like conformation, with a larger cavity delimited by two syn 3,5-dimethoxyphenyl moieties, and two external pockets, each delimited by the other 3,5-dimethoxyphenyl group and its diamido arm (the wing). Complexation phenomena were investigated by nuclear magnetic resonance (NMR) methods, including (1)H NMR DOSY and 1D ROESY experiments, and molecular modeling. Heteroassociation constants of [(all-S)-1·2] and [(all-R)-1·2] diastereoisomeric complexes were obtained from diffusion data by single point measurements, and from nonlinear fitting of 1H NMR chemical shifts. Selective proton relaxation rate measurements allowed us to significantly discriminate the two complexes by identifying two different interaction sites of the guest in the resorcin[4]arene host, depending on its configuration.

Topics: Calixarenes; Deoxycytidine; Magnetic Resonance Spectroscopy; Models, Molecular; Phenylalanine; Stereoisomerism

Calixresorcinarenes have proved to be unique molecules for molecular recognition via hydrogen bonding, hydrophobic and ionic interactions with suitable substrates such as cations. The study of the interactions involved in the complexation of different cations with calixresorcinarenes in solvent mixtures is important for a better understanding of the mechanism of biological transport, molecular recognition, and other analytical applications. This article summarizes different aspects of the complexes of the Ti(3+) metal cation with c-methylcalix[4]resorcinarene (CMCR) as studied by conductometry in acetonitrile (AN)-water (H₂O) binary mixtures at different temperatures. Conductance data show that the metal cation/ligand (ML) stoichiometry of the complexes in solution is 1:1 in all cases. Non-linear behaviour was observed for the variation of logKf of the complexes vs. the composition of the binary solvent mixtures. Selectivity of CMCR for the Ti(3+) cation is sensitive to solvent composition; in some cases and at certain compositions of the mixed solvent systems, the selectivity order is changed. Values of thermodynamic parameters (ΔH(c)(0), ΔS(c)(0)) for formation of the CMCR-Ti(3+) complexes in AN-H₂O binary systems were obtained from the temperature dependence of stability constants, and the results show that the thermodynamics of complexation reactions are affected by the nature and composition of the mixed solvents.

Topics: Acetonitriles; Calixarenes; Coordination Complexes; Electric Conductivity; Phenylalanine; Solutions; Solvents; Thermodynamics; Titanium; Water

Molecular capsules have attracted interest as simple enzyme mimetics and several examples of catalytic transformations in water-soluble metal-ligand based systems have been reported. This is not the case for hydrogen-bond based molecular capsules, which in contrast can be employed in organic solvents. We describe herein our investigations of such a system: The resorcin[4]arene hexamer is one of the largest hydrogen bond-based self-assembled capsules and has been studied intensively due to its ready availability. We present evidence that the capsule acts as a reasonably strong Brønsted acid (pKa approximately 5.5-6). This finding explains the capsule's high affinity toward tertiary amines that are protonated and therefore encounter cation-π interactions inside the cavity. We were able to translate this finding into a first synthetic application: A highly substrate-selective Wittig reaction. We also report that this property renders the capsule an efficient enzyme-like catalyst for substrate selective diethyl acetal hydrolysis.

Topics: Acetals; Ammonium Compounds; Calixarenes; Catalysis; Crystallography, X-Ray; Electron Spin Resonance Spectroscopy; Hydrogen Bonding; Hydrogen-Ion Concentration; Hydrolysis; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Molecular Conformation; Phenylalanine; Protons

C-5-bromo-2-hydroxyphenylcalix[4]-2-methylresorcinarene (I) was synthesized by cyclocondensation of 5-bromo-2-hydroxybenzaldehyde and 2-methylresorcinol in the presence of concentrated HCl. Compound I was characterized by infrared and nuclear magnetic resonance spectroscopic data. X-ray analysis showed that this compound crystallized in a triclinic system with space group of Pī, a = 15.9592(16)Å, b = 16.9417(17)Å, c = 17.0974(17)Å, α = 68.656(3)°, β = 85.689(3)°, γ = 81.631(3)°, Z = 2 and V = 4258.6(7)Å3. The molecule adopts a chair (C2h) conformation. The thermal properties and antioxidant activity were also investigated. It was strongly antiviral against HSV-1 and weakly antibacterial against Gram-positive bacteria. Cytotoxicity testing on Vero cells showed that it is non-toxic, with a CC50 of more than 0.4 mg/mL.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Antiviral Agents; Calixarenes; Chlorocebus aethiops; Crystallography, X-Ray; Herpesvirus 1, Human; Molecular Structure; Phenylalanine; Thermogravimetry; Vero Cells

Electrospray ionisation mass spectrometry (ESI-MS) has been used to study the relative gas-phase proton and alkali metal (Li, Na, K and Cs) binding affinities of three different resorcin[4]arenes using the kinetic method. Collision-induced dissociation (CID) was used to study the fragmentation of resorcin[4]arene heterodimer sandwich complexes, allowing the relative binding affinity order to be established. All the alkali metal cations have the same gas-phase binding affinity order with the resorcin[4]arene host molecules. At collision energies of > or = 13eV, one of the [resorcin[4]arene+Metal]+, (Metal = Li, Na, K) ions fragmented through break-up of the resorcin[4]arene, whilst the other host resorcin[4]arene remained intact, causing an apparent change in binding affinity at high collision energy. This effect was not observed with caesium, since all complex ions dissociated readily under CID by displacement of the caesium cation. The binding affinity for the protonated resorcin[4]arenes was found to be different from the alkali metal cation binding affinity because of the higher proton affinity of the nitrogen-containing resorcin[4]arenes. It is shown that resorcin[4]arenes containing an oxazine ring can be converted into a ring-opened derivative via an Eschweiler-CLarke reaction in the presence of formic acid. A second ring-opening process also occurs, including a hydrolysis reaction that results in apparent Losses of 12 mass units from the intact resorcin[4]arene. Both these reactions occur in solution before mass spectrometric investigation and cannot be achieved by CID. This observation was confirmed by inducing the Eschweiter-CLarke reaction in a model benzoxazine compound.

Topics: Binding Sites; Calixarenes; Coordination Complexes; Gases; Kinetics; Metals, Alkali; Oxazines; Oxidation-Reduction; Phenylalanine; Protons; Solutions; Spectrometry, Mass, Electrospray Ionization

In this work, a cationic star polymer [poly(2-dimethylamino)ethyl methacrylate (PDMAEMA)] was prepared via atom transfer radical polymerization (ATRP), using brominated calix[4]resorcinarene as an initiator. Hydrophobic moieties, methyl methacrylate (MMA) and butyl acrylate (BA), were further incorporated via "one-pot" method. Well-defined eight-armed star block copolymers bearing hydrophilic blocks inside and hydrophobic blocks outside were synthesized. The molecular weight, particle size, electrophoretic mobility and apparent charge density were determined by gel permeation chromatography (GPC), dynamic light scattering (DLS), phase analysis light scattering (PALS) and colloidal titration, respectively. The zeta potentials and apparent charge densities of the products exhibited the characteristics of polyelectrolyte. The incorporation of hydrophobic moieties generated electrostatic screening effect. The as-synthesized amphiphilic star copolymer is promising as a thermo-sensitive gene carrier for gene therapy.

Topics: Calixarenes; Chromatography, Gel; Electrophoresis; Kinetics; Methacrylates; Methylmethacrylate; Nylons; Particle Size; Phenylalanine; Polymerization; Proton Magnetic Resonance Spectroscopy; Static Electricity

A resorcinarene-based macrocyclic ligand functionalized with alanine and undecyl groups (AUA) was synthesized and applied to ion chromatographic separations. The selectivity and separation of transition metal ions on a column packed with AUA adsorbed onto 55% cross-linked styrene-divinylbenzene resin are presented. The upper and lower rims of the resorcinarene were modified with amino acids and -C(11)H(23) alkyl chains, respectively. The four carboxylic acid groups on the upper rim act as cation-exchangers while the four -C(11)H(23) alkyl chains serve to anchor the ligand to the resin surface by the hydrophobic effect. A systematic study of the effect of different eluent components including non-metal-chelating (HNO(3)) and chelating acids (oxalic acid, succinic acid, dipicolinic acid, and citric acid) on the retention of transition metal ions was investigated. Six metal ions (Mn(2+), Co(2+), Ni(2+), Cd(2+), Cu(2+), and Zn(2+)) were separated on the AUA column within a reasonable time with a single eluent gradient using oxalic acid. The separation is compared to that obtained using a commercial column containing carboxylic acid functional groups. The AUA column containing four preorganized carboxylic acid groups showed selectivity for Cu(2+) when no chelating eluent was present, a selectivity which was not observed with the comparison column.

Topics: Alanine; Amino Acids; Calixarenes; Carboxylic Acids; Cations, Divalent; Chelating Agents; Chromatography, Ion Exchange; Macrocyclic Compounds; Metals; Phenylalanine; Sensitivity and Specificity; Transition Elements

Eleven resorcinarene cavitands bearing either one, two or four (3-R-1-imidazolylium)-methyl substituents (R = (n)Bu, Ph, Mes, (i)Pr(2)C(6)H(3)) anchored at resorcinolic "ortho" positions have been synthesised from the appropriate bromomethylated precursor. Combining the imidazolium salts with palladium acetate and Cs(2)CO(3) gave active Suzuki-Miyaura cross coupling catalysts. The highest activities were observed with the doubly functionalised cavitands, which all have the imidazolylium groups attached to proximal resorcinol units.

Topics: Calixarenes; Catalysis; Hydrocarbons, Aromatic; Imidazoles; Ligands; Models, Molecular; Molecular Conformation; Phenylalanine; Salts

A series of resorcinaren-PAMAM dendrimers with benzodiazepines in the periphery were synthesized and their anticancer properties studied. The synthesized dendrimers showed potential anticancer activities, which were enhanced in the presence of a chloro-substituent in the second ring of the 5-aryl-1,4-benzodiazepine. The dendrimers were characterized by IR, (1)H and (13)C NMR, UV-vis absorption, electrospray (ES) and/or MALDI-TOF mass spectrometries.

Topics: Antineoplastic Agents; Benzodiazepines; Calixarenes; Cell Line, Tumor; Crystallography, X-Ray; Dendrimers; Drug Screening Assays, Antitumor; Humans; Molecular Conformation; Phenylalanine

The effect of cyclochirality of rccc-2,8,14,20-tetra-n-decyl-4,10,16,22-tetra-O-methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano-electrospray ionization (nano-ESI)-Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton-bound [C·H·G](+) complexes by nano-ESI of solutions containing an equimolar amount of quasi-enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision-induced dissociation experiments on some of the relevant [C(2) ·H·G](+) three-body species and Density functional theory (DFT) calculations performed on the most selective systems.

Topics: Calixarenes; Fourier Analysis; Gases; Kinetics; Macrocyclic Compounds; Models, Molecular; Phenylalanine; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism

Silver complexes of a cation binding supramolecular host, resorcinarene bis-crown (CNBC5) with propyl, nonyl, decyl and undecyl alkyl chains were investigated by NMR titration, picrate extraction and single crystal X-ray diffraction. Binding studies showed that both 1 : 1 and 1 : 2 (host-Ag(+)) complexes are present in solution with only a slight effect of the lower rim alkyl chain length on the binding constants (log K 4.0-4.2 for 1 : 2 complexes). Solid state complexes of the resorcinarene bis-crowns bearing either C(3) or C(11) chains were obtained. Single crystal X-ray analyses showed that both derivatives bind silver ions by metal-arene and Ag···O coordination from the crown ether bridges and from the solvent, and pack in layered or bilayered fashion. Furthermore, the amphiphilic nature of C11BC5 was demonstrated using the Langmuir balance technique. Langmuir-Blodgett films of the amphiphilic C11BC5-Ag complex were transferred onto a substrate and shown to possess antibacterial activity against E. coli.

Topics: Anti-Bacterial Agents; Calixarenes; Coordination Complexes; Crystallography, X-Ray; Escherichia coli; Escherichia coli Infections; Molecular Structure; Phenylalanine; Silver

Nano- and micrometer-scale crystals of a self-assembled hexamer have been synthesized via sonochemistry. The application of ultrasonic irradiation afforded hollow rhombic-dodecahedral crystals of the C-methylcalix[4]resorcinarene hexamer. The formation of the hollow crystals is attributed to a reversed crystal growth mechanism heretofore described only in the synthesis of inorganic-based materials.

Topics: Calixarenes; Models, Molecular; Nanoparticles; Particle Size; Phenylalanine; Porosity; Surface Properties; Ultrasonics

The non-covalent interactions of different upper-rim-substituted C(2)-resorcinarenes with tetramethylammonium salts were analyzed in the gas phase in an Electrospray Ionization Fourier-transform ion-cyclotron-resonance (ESI-FTICR) mass spectrometer and by (1)H NMR titrations. The order of binding strengths of the hosts towards the tetramethylammonium cation in the gas phase reflects the electronic nature of the substituents on the upper rim of the resorcinarene. In solution, however, a different trend with particularly high binding constants for halogenated resorcinarenes has been observed. This trend can be explained by a synergetic effect originating from the interaction of the halogenated resorcinarenes with the counter anions through hydrogen bonding. This study highlights the importance of weak interactions in recognition processes and points out the benefits of comparing the gas-phase data with results obtained from solution experiments.

Topics: Calixarenes; Halogenation; Hydrogen Bonding; Ions; Magnetic Resonance Spectroscopy; Models, Molecular; Phenylalanine; Quaternary Ammonium Compounds; Salts; Spectrometry, Mass, Electrospray Ionization

The selectivity and separation of transition metal ions on two columns packed with cyclen-based macrocycles adsorbed onto 55% cross-linked styrene-divinylbenzene resin are presented. The N-cyclen and cyclen-resorcinarene stationary phases were made by adsorbing hydrophobically substituted N-cyclen or a cyclen-resorcinarene derivative (cyclenbowl) on the resin, respectively. The stability constants of cyclen with transition metal ions demonstrate that cyclen has selectivity for Cu²⁺ over other transition metal ions. Mn²⁺, Co²⁺, Ni²⁺, Cd²⁺, and Zn²⁺ ions were separated from Cu²⁺ using HNO₃ eluent with the cyclenbowl column. The preconcentration of Cu²⁺ in parts per billion level from a high concentration matrix of Mn²⁺, Co²⁺, Ni²⁺, Cd²⁺, and Zn²⁺ ions was achieved in the cyclenbowl column using a nitric acid eluent gradient. Recovery of Cu²⁺ at >98% was obtained based on direct interaction of metal ion and cyclen. Although Mn²⁺, Co²⁺, Ni²⁺, Cd²⁺, and Zn²⁺ were not separated by HNO₃ eluent, addition of oxalic acid yielded a very good separation. A retention mechanism is proposed for the latter system in which the protonated cyclen units attract negatively charged HC₂O₄⁻ ions that cooperate with cyclen sites in retaining transition metal ions.

Topics: Calixarenes; Cations; Chromatography, Liquid; Cyclams; Heterocyclic Compounds; Phenylalanine

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (AMA), alanine undecyl resorcinarene acid (AUA) and glycine undecyl resorcinarene acid (GUA), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of AMA, AUA, and GUA with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary L-tartaric acid and the monoacid phthalyl alanine (PA). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary L-tartaric acid only binds one amine guest strongly. The simple compound PA, which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of AUA with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.

Topics: Amines; Amino Acids; Calixarenes; Ethers, Cyclic; Molecular Structure; Phenylalanine; Resorcinols; Stereoisomerism

Diquinone-based resorcin[4]arene cavitands that open to a kite and close to a vase form upon changing their redox state, thereby releasing and binding guests, have been prepared and studied. The switching mechanism is based on intramolecular H-bonding interactions that stabilize the vase form and are only present in the reduced hydroquinone state. The intramolecular H-bonds were characterized using X-ray, IR, and NMR spectroscopies. Guests were bound in the closed, reduced state and fully released in the open, oxidized state.

Topics: Calixarenes; Ethers, Cyclic; Models, Molecular; Molecular Structure; Oxidation-Reduction; Phenylalanine; Resorcinols

Reversible encapsulation of [Ru(bpy)(3)](2+) within a self-assembled hexameric resorcin[4]arene capsule turns off the photocatalytic aerobic oxidation of an aliphatic sulfide. Upon addition of a competitive cationic guest, the Ru(II) catalyst is released into solution where its catalytic activity is restored.

Topics: Calixarenes; Catalysis; Light; Organometallic Compounds; Oxidation-Reduction; Phenylalanine

The gas-phase encounters between 2-aminobutane and proton-bound chiral resorcin[4]arene/nucleoside complexes behave in the gas phase as supramolecular "chiroselective logic gates" by releasing the nucleoside depending on the resorcin[4]arene and the 2-aminobutane configurations.

Topics: Amines; Butanes; Calixarenes; Gases; Hydrophobic and Hydrophilic Interactions; Macrocyclic Compounds; Molecular Conformation; Phenylalanine; Stereoisomerism

The encapsulation of a Au(I) catalyst within a self-assembled, hydrogen bonded, hexameric capsule dramatically changes its catalytic activity, leading to unusual products due to the steric requirements of the host's cavity.

Topics: Calixarenes; Catalysis; Gold; Hydrogen Bonding; Models, Molecular; Phenylalanine; Solvents; Stereoisomerism

The synthesis of a cavitand featuring thiourea hydrogen bonding sites and its dimerization in the presence of suitable guests are reported. Dimerization creates a capsule host wider than the corresponding urea or imide structures, and longer alkanes can be accommodated. Specifically, n-C(15)H(32) is encapsulated, but this guest appears folded inside as deduced from NMR studies. Apparently, the plasticity of hydrogen bonds between thiourea groups allows a stable encapsulation complex to persist in solution even though the guest is contorted.

Topics: Alkanes; Calixarenes; Capsules; Models, Molecular; Molecular Conformation; Phenylalanine; Thiourea

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties.

Topics: Calixarenes; Cations; Conductometry; Magnetic Resonance Spectroscopy; Phenylalanine; Piperazines; Potentiometry; Solubility; Sulfonic Acids; Surface-Active Agents

Synthetic multivalent glycoclusters show promise as anti-adhesives for the treatment of bacterial infections. Here we report the synthesis of a family of tetravalent galactose and lactose functionalised macrocycles based on the resorcin[4]arene core. The development of diastereoselective synthetic routes for the formation of lower-rim propargylated resorcin[4]arenes and their functionalistion via Cu-catalyzed azide-alkyne click chemistry is described. ELLA binding studies confirm that galactose sugar clusters are effective ligands for the PA-IL bacterial lectin of Pseudomonas aeruginosa while poor binding for the lactose-based monovalent probe and no binding could be measured for the multivalent glycoclusters was observed for the human galectin-1.

Topics: Alkynes; Azides; Calixarenes; Catalysis; Chemistry Techniques, Synthetic; Click Chemistry; Copper; Crystallography, X-Ray; Galactose; Galectin 1; Humans; Lactose; Lectins; Ligands; Models, Molecular; Molecular Structure; Phenylalanine; Pseudomonas aeruginosa; Stereoisomerism; Structure-Activity Relationship

Two new types of methylcalix[4]resorcinarene-bonded stationary phases, (3-(C-methylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MCR-HPS) and bromoacetate-substituted MCR-HPS particles (BAMCR-HPS), have been synthesized and used as chiral stationary phases for high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phases are characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. The chromatographic behavior of MCR-HPS and BAMCR-HPS was studied with several disubstituted benzenes and some chiral drug compounds under both normal phase and reversed-phase conditions. The results show that MCR-HPS has excellent selectivity for the separation of aromatic positional isomers and BAMCR-HPS exhibits excellent performance for separation of enantiomers of chiral compounds.

Topics: Acetates; Benzene; Calixarenes; Chemistry, Pharmaceutical; Chromatography; Chromatography, High Pressure Liquid; Hydrogen Bonding; Isomerism; Models, Chemical; Molecular Conformation; Pharmaceutical Preparations; Phenylalanine; Resorcinols; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared; Stereoisomerism

Selectively functionalized resorcinarenes were obtained by weak-base-promoted O-alkylation of C-undecylresorcin[4]arene 1. Tetrasubstituted derivatives with C(4)-1,3,5,7, C(2v)-1,2,5,6, C(s)-1,2,4,7, and C(i)-1,2,4,6 pattern were obtained in workable yields by using K(2)CO(3) as the base in acetone at reflux. The good regioselectivity with respect to the statistical distribution was explained in terms of preferential formation of H-bonded monoanions. Heptaaroylated resorcin[4]arenes were also easily obtained by reaction of 1 with aroyl chlorides in pyridine.

Topics: Calixarenes; Models, Molecular; Molecular Structure; Phenylalanine; Stereoisomerism

Resorcinarene-based cavitands functionalized with acetamido groups capable of self-complementary hydrogen-bond interactions, were synthesized in order to construct supramolecular capsules. The 1,3-bifunctionalized cavitand produced a polymeric assembly, whereas the tetra-functionalized analogue yielded a discrete capsule held together via N-H···O hydrogen bonds. The ethynyl species attached to the rim of these host molecules deepen each cavitand and expands the volume of the resulting capsule.

Topics: Aminopyridines; Calixarenes; Ethers, Cyclic; Hydrogen Bonding; Molecular Conformation; Molecular Structure; Phenylalanine; Resorcinols

The host-guest properties of a water-soluble resorcinarene cavitand bearing four guanidines at the feet were investigated in water and dodecylphosphocholine (DPC) micelles by NMR spectroscopy. While the binding of different guests in water was generally modest, the formation of the caviplexes was significantly enhanced in the presence of micelles and reached affinities typically observed for organic solvents. The increase in binding free energies of up to 3.2 kcal mol(-1) was determined to be enthalpic in origin and was attributed to the disruption of velcrand dimers and subsequent conformational reorganization of the receptor induced by the micelles that acted as hosts for the cavitand. In agreement with the NMR data, molecular dynamics simulations reproduced the spontaneous incorporation of the cavitand into the micelle and provided a detailed picture of the positioning of the receptor at the DPC-water interface.

Topics: Calixarenes; Magnetic Resonance Spectroscopy; Micelles; Models, Molecular; Molecular Conformation; Phenylalanine; Phosphorylcholine; Solubility; Water

Herein we present the synthesis and the photochemical behavior of several new hemicarcerands containing anthracene units as photoactive species. By means of NMR investigations of compounds 9 and 11 the dimerization mode was revealed as a 9,10-9',10'-dimerization, classically known from anthracene. Nevertheless only compound 11 could be converted to the opened form upon irradiation with 300 nm. Reopening of compounds 9 and 10 could not be achieved so far either by heating or by irradiation.

Topics: Anthracenes; Calixarenes; Capsules; Dimerization; Molecular Structure; Phenylalanine; Photochemical Processes; Stereoisomerism

The complexation properties of two novel C5-substituted adamantanediazirines within the resorcin[4]arene-based cavitand 4 were investigated in DMSO-d(6), revealing that binding is up to 1.4 kcal/mol stronger for halogenated adamantanediazirines when compared with the unsubstituted species. The thermal behavior of 5-bromo-2-aziadamantane (3) was investigated by DSC analysis as the first representative of the adamantanediazirine family in the neat solid state, as well as encapsulated within the aromatic cavity of cavitand 4. In the solid phase, the reactions of photolytically or thermolytically generated 5-bromo-2-adamantanylidene (11) can be controlled by complexation within cavitand 4.

Topics: Adamantane; Calixarenes; Molecular Conformation; Phenylalanine; Stereoisomerism; Temperature

The one-pot Mannich condensation of resorcinarenes with piperazine and an excess of formaldehyde under high dilution conditions results in a helical cage, namely, a covalently linked dimer of two resorcinarenes connected via four piperazine bridges in yields ranging from 20 to 40%. The compounds were analyzed by NMR spectroscopy, ESI mass spectrometry, and single crystal X-ray diffraction. The helical cages can encapsulate small guest molecules by adapting the cavity volume by changing the helical pitch according to the guest size.

Topics: Calixarenes; Crystallography, X-Ray; Models, Molecular; Molecular Conformation; Phenylalanine; Piperazine; Piperazines; Stereoisomerism

The condensation of a Kemp's triacid derivative with a diamino resorcinarene yielded a cavitand with the deepest cavity prepared to date featuring an inwardly-directed carboxylic acid. The extended 6,7-diaminoquinoxaline wall bearing the acid allowed accommodation of large amines, such as 1-adamantanemethylamine, as well as smaller amines such as triethylamine. Adamantyl and cyclohexyl isocyanides are also bound in the deep cavitand in a way that positions the isonitrile function near the carboxylic acid group. Reaction occurs inside the cavity at ambient temperature to form the respective N-acylformamides. Low concentrations of the transient O-acyl isoamide intermediate were detected by (1)H NMR and IR spectroscopy.

Topics: Amines; Calixarenes; Carboxylic Acids; Ethers, Cyclic; Magnetic Resonance Spectroscopy; Phenylalanine; Resorcinols; Spectrophotometry, Infrared; Temperature

Resorcin[4]arene cavitand 1 with 1,3,2-benzodiazaborolyl walls was newly synthesized. It showed a large blue shift in the fluorescence spectra upon selective complexation with alkyltrimethylammonium salts in CH(2)Cl(2)-DMSO (9 : 1 v/v); this shift was detectable with the naked eye.

Topics: Boron Compounds; Calixarenes; Cations; Fluorescent Dyes; Molecular Structure; Phenylalanine; Quaternary Ammonium Compounds; Stereoisomerism

Solid C-methylcalix[4]resorcinarene solvated by acetonitrile and water (CAL-Me) and then modified by slow solvent evaporation (CAL-Me*) was studied using single-crystal and powder X-ray diffraction, FT-IR, and (13)C CP/MAS NMR. The CAL-Me solvate crystallizes in the monoclinic P2(1)/n space group with three CH(3)CN and two H(2)O molecules in the asymmetric part of the unit cell. The CAL-Me molecules adopt a typical crown conformation with all of the hydroxyl groups of the aryl rings oriented up and all of the methyl groups disposed down (the rccc isomeric form). The crystalline network is formed by resorcinarene, CH(3)CN, and H(2)O molecules and assembled by intermolecular hydrogen bonds and weak C-H...A or C-H...pi interactions. The desolvated CAL-Me* loses its crystalline character and becomes partly amorphous. It is devoid of CH(3)CN and deficient in water. However, the resorcinarene molecules still remain in the crown conformation supported by intramolecular hydrogen bonds, while intermolecular hydrogen bonds are considerably disintegrated. The work directs general attention to the problem of stability and polymorphism of resorcinarene solvates. It shows that the joint use of diffractometric and spectroscopic methods is advantageous in the structural studies of complex crystalline macromolecular systems. On the other hand, the solid-state IR and NMR spectroscopic analyses applied in tandem have been found highly beneficial to elucidate the disordered structure of poorly crystalline, desolvated resorcinarene.

Topics: Acetonitriles; Calixarenes; Crystallography, X-Ray; Hydrogen Bonding; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phenylalanine; Solvents; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

Topics: Calixarenes; Drug Design; Molecular Structure; Nanoparticles; Phenylalanine; Surface-Active Agents

Water-soluble calix[4]resorcinarenes with proline, 3-hydroxyproline, and 4-hydroxyproline substituent groups are evaluated as chiral NMR solvating agents on a series of bicyclic aromatic compounds with naphthyl, indole, dihydroindole, and indane rings. The substrates interact with the calixresorcinarene through insertion of the aromatic ring into the cavity. Most of the substrates are analyzed as cationic species, although one anionic species is analyzed. All of the substrates exhibit enantiomeric discrimination in the 1H-NMR spectrum with one or more of the calixresorcinarenes. In most cases, the hydroxyproline derivatives are more effective at causing enantiodifferentiation than the corresponding proline derivative. Presumably, the hydroxyl group on the proline moieties is involved in interactions with the substituent groups of the substrate that are important in creating chiral recognition. The enantiomeric discrimination in the 1H-NMR spectrum is large enough for many resonances to permit the analysis of enantiomeric purity.

Topics: Bridged Bicyclo Compounds; Calixarenes; Hydroxyproline; Magnetic Resonance Spectroscopy; Molecular Structure; Phenylalanine; Solubility; Solvents; Stereoisomerism; Water

The formation of capsule-like dynamic assemblies which do not rely on attractions between host subunits was achieved via specific interactions with fluorinated guests. Characterization of these three component assemblies was accomplished by applications of (19)F NMR spectroscopy.

Topics: Adamantane; Alkynes; Calixarenes; Ethers, Cyclic; Fluorine; Hydrocarbons, Fluorinated; Iodobenzenes; Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine; Resorcinols

Resorcinarene oxazines bearing four TEMPO fragments at the wide rim of the macrocycle were prepared through the aminomethylation of resorcinarene octols with 4-amino-TEMPO and formaldehyde. Tetra-TEMPO resorcinarenes are efficient scavengers of 1,1-diphenyl-2-picrylhydrazyl radicals. The model studies revealed that macrocyclic structure and intramolecular hydrogen bonding make considerable contribution to antiradical activity of these compounds. Tetra-TEMPO resorcinarenes show also superoxide dismutase-like activity and efficiently inhibit ABAP-induced peroxidation of linoleic acid.

Topics: Antioxidants; Binding, Competitive; Calixarenes; Free Radical Scavengers; Free Radicals; Nitrogen Oxides; Phenylalanine; Superoxides

Highly crystalline directional poly(epsilon-caprolactone) based on a tetrahydroxymethyl resorcin[4]arene initiator core was synthesized by a "core first" method via ring-opening polymerization catalyzed by Sn(Oct)(2) in bulk at 120 degrees C.

Topics: Calixarenes; Caprylates; Catalysis; Ethers, Cyclic; Phenylalanine; Polyesters; Resorcinols

Phenylalanine substituted resorcinarenes form self-complementary dimeric homo- or heterochiral capsules based on deeply buried electrostatic interactions (salt bridges) with numerous polar and non-polar functionalities in their interiors available for interactions with encapsulated polar molecules, as proved by X-ray analysis and diffusion NMR spectroscopy.

Topics: Calixarenes; Crystallography, X-Ray; Dimerization; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Structure; Phenylalanine

The stereoselectivity of the reaction between (R)-(-)-2-butylamine and the diastereomeric proton-bound complexes of (+)-catharanthine (C) or (-)-vindoline (V) with some chiral amido[4]resorcinarenes has been investigated in the gas phase by ESI-FT-ICR-MS. The reaction stereoselectivity (0.56 < k(homo)/k(hetero) < 16.9) is found to depend critically on the functional groups present in the chiral pendants of the hosts. Rationalisation of the kinetic results is based on careful computational and spectroscopic studies of the most stable conformations of (+)-catharanthine and its protonated form in the isolated state and in water, as well as in a representative host structure. The emerging picture points to the relevant diastereomeric proton-bound complexes as quasi-degenerate, thus suggesting that their stereoselectivity in the guest exchange reaction is mostly due to kinetic factors. The results of this study may represent a starting point for a deeper comprehension of the intrinsic factors that endow these molecules, and their dimeric forms, with their biochemical properties.

Topics: Amines; Calixarenes; Carbon; Hydrocarbons; Kinetics; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Molecular Structure; Phenylalanine; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Vinca Alkaloids

Self-assembled, hydrogen-bonded capsules emerge from synthetic resorcinarene-derived cavitands and soluble glycolurils when appropriate guest molecules are present. The assembly consists of 2 cavitands, 4 glycolurils and guest(s), and the arrangement of glycolurils leads to a chiral structure. The capsule features a space of approximately 620 A(3) and accommodates narrow guests such as n-alkanes from C(14) to C(19), or other molecules (e.g., capsaicin) and combinations of molecules of up to approximately 22 A in length (e.g., two p-methylstyrene molecules). Positions of encapsulated nuclei can be predicted from NMR chemical shifts, with intense shielding of deltaDelta = -5 ppm near the resorcinarene ends and mild deshielding of +0.5 to 1 ppm near the glycolurils at the capsule's center. Computational methods using nucleus independent chemical shifts (NICS) were used to map the induced magnetic shielding/deshielding for the inner space of the cavity. The asymmetric arrangement of the spacers creates a chiral steric and magnetic environment in the capsule and the geminal hydrogen atoms of encapsulated alkanes show diastereotopic proton signals. The two enantiomers interconvert (racemize) through an achiral intermediate involving a slight rotation of the spacers and lengthening of the cavity. Accordingly, longer, compressed alkanes accelerate the racemization by applying pressure from the inside on the capsule's ends. Guests that place hydrogen bond donors and acceptors near the glycolurils in the middle (e.g., p-isopropylbenzyl alcohol) also accelerate the racemization by facilitating the rotation of the glycolurils. Slow tumbling of guest on the NMR time scale inside the capsule leads to social isomerism of para-disubstituted benzenes such as p-methylstyrene. Flexible guests such as hexane tumble inside the cavity with an activation barrier of DeltaG(++) =16.2 kcal/mol. The middle of the extended capsule is narrow, but still accommodates phenyl groups such as those presented by p-quaterphenyl and alkylated biphenylcarbonitriles. The aromatic units in these guests report their positions by imparting magnetic anisotropy to the capsule components. Gases such as propane, butane, isobutane, propylene, 2-methylpropene, and 1,3-butadiene even xenon are coencapsulated with other guests and their motions inside are examined.

Topics: Alkenes; Butadienes; Butanes; Calixarenes; Capsaicin; Chemistry, Organic; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Magnetics; Models, Chemical; Molecular Conformation; Phenylalanine; Propane; Stereoisomerism; Thermodynamics

Capsule-shaped molecular receptors are fundamental to the modeling of biological host-guest interactions such as those characteristic of enzymatic processes. Among the more versatile and effective synthetic receptors are the hemicarcerand-type hosts. Herein we report the synthesis of six novel resorcin[4]arene cavitand-capped porphyrin capsules, in a new series of molecular capsules modeled on the classical hemicarcerands initially reported by Cram and co-workers. In the first reported instance of its utilisation in the preparation of supramolecularly-capped porphyrin host molecules, microwave (MW) irradiation was used (in conjunction with Adler conditions) in order to form the porphyrin cap in situ. Additionally, the yields obtained via these conditions exhibited a significant improvement, relative to the traditional refluxing protocol hitherto reported. Capsules 20-25 are indefinitely stable, and we observed that 22 and 25 possess the smallest rigidified cavities yet reported for resorcin[4]arene cavitand-capped porphyrin host molecules.

Topics: Calixarenes; Capsules; Ethers, Cyclic; Hot Temperature; Magnetic Resonance Spectroscopy; Microwaves; Phenylalanine; Porphyrins; Resorcinols

A new method is described for the simultaneous preconcentration of trace metal ions. The method is based on the adsorption of Co(2+), Ni(2+), Cu(2+) and Cd(2+) ions on 2,4,6,8-tetra(2-hydroxyphenyl)-1,3,5,7(1,3)tetrabenzenzcyclooctaphane-14,16,34,36,54, 56,74,76-octol (salicylaldehyde calix[4] resorcinarenes) (new resorcinarenes derivative) modified on Amberlite XAD-16. The adsorbed analyte ions were eluted with 6 mL 3M HCl in acetone solution, which then were determined by atomic absorption spectroscopy. The influences of the analytical parameters including pH, ligand amount and solid phase ingredient, eluting solution conditions and sample volume were investigated. Common coexisting ions did not interfere with the separation and determination. The preconcentration factor is 208. The sorbent exhibited excellent stability and its sorption capacity under optimum conditions has been found to be more than 60 microg of ions per gram of sorbent. The relative standard deviation under optimum conditions is lower than 4.10%. The accuracy of the method was estimated by using different real samples.

Topics: Cadmium; Calixarenes; Cobalt; Copper; Hydrogen-Ion Concentration; Metals, Heavy; Nickel; Phenylalanine; Polymers; Solid Phase Extraction

N-undecyl cyclen and a resorcinarene bowl bearing four cyclen arms have been applied as anion exchangers in ion chromatography by strong adsorption to a reversed-phase column. The column loaded with the resorcinarene bowl cyclen tetramer exhibited significantly better performance in anion separation than that with N-undecyl cyclen monomer in isocratic elution mode. Both columns were tested for polarizable anion preconcentration or removal. By changing the eluent type from sodium bicarbonate to sodium hydroxide, the degree of protonation of the cyclen molecules could be modified, and the column capacity for anion retention adjusted thereby. Capacity gradient elution was successfully applied to removing sample matrix ions in the preconcentration of perchlorate and perrhenate ions as example analytes.

Topics: Anions; Calixarenes; Chromatography, Liquid; Cyclams; Environmental Pollutants; Heterocyclic Compounds; Perchlorates; Phenylalanine; Sodium Pertechnetate Tc 99m

The synthesis and structural properties of tetramethoxy resorcinarene mono-crown-5 (1) are described. The binding characteristics of 1 toward acetylcholine and tetramethylammonium salts were investigated by 1H NMR titration. It was observed that the cavity of 1 provides a better fit to acetylcholine compared to the smaller tetramethylammonium cation, as acetylcholine is able to interact with both the crown ether moiety and the free hydroxyl groups of receptor 1 simultaneously.

Topics: Binding Sites; Calixarenes; Crown Compounds; Hydroxides; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine; Quaternary Ammonium Compounds

Pyrogallol[4]arene macrocycles prepared from pyrogallol and n-dodecanal insert in phospholipid bilayers and form conducting pores that undergo reversible switching over a wide range of potentials.

Topics: Calixarenes; Ion Channels; Lipid Bilayers; Membrane Potentials; Molecular Structure; Phenylalanine; Phospholipids; Porosity; Pyrogallol

Water stabilized, deep cavitands with three walls and an open side are shown to be receptors for amines and ammonium cations bearing bulky aliphatic groups. The missing wall allows the binding of guests not accommodated by the four-walled counterparts.

Topics: Adamantane; Calixarenes; Ethers, Cyclic; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine; Quaternary Ammonium Compounds; Resorcinols; Water

An acid-sensitive semiperfluoroalkyl resorcinarene was synthesized, and its lithographic properties were evaluated. Its solubility in segregated hydrofluoroether solvents enables the patterning of delicate organic electronic materials.

Topics: Calixarenes; Electrochemistry; Electronics; Hydrocarbons, Fluorinated; Phenylalanine

Rotaxane-type receptors, which were composed of anionic cyclophane-based resorcinarene tetramers as the wheel and a 2,6-disubstituted naphthalene derivative having two fluorophore moieties, such as fluorescein and rhodamine residues, as the axle ( and , respectively), were prepared. Rotaxane-type receptors and bound histone, a small basic protein component of eukaryotic chromatins, with binding constants of 2.3 x 10(6) and 9.0 x 10(5) M(-1), respectively. The rotaxane-type receptors showed fluorescence sensing ability with remarkable histone selectivity. Moreover, fluorescence resonance energy transfer (FRET) between the fluorescein residues of and the rhodamine residues of took place in the presence of histone, which was a useful method for the detection of histone.

Topics: Calixarenes; Fluorescein; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Histones; Molecular Structure; Phenylalanine; Rhodamines; Rotaxanes; Spectrometry, Fluorescence

Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

Topics: Bacterial Proteins; Calixarenes; DNA; Microscopy, Atomic Force; Molecular Structure; Phenylalanine; Photochemistry; Protein Engineering; Sinorhizobium meliloti; Spectrum Analysis; Stress, Mechanical; Temperature; Ultraviolet Rays

Water-soluble calix[4]resorcinarenes containing 3- and 4-hydroxyproline, d-nipecotic acid, (S)-2-(methoxymethyl)pyrrolidine, (S)-2-pyrrolidine methanol, and (S,S)-(+)-2,4-bis(methoxymethyl)pyrrolidine substituents are synthesized and evaluated as chiral NMR solvating agents. The derivatives with the hydroxyproline groups are especially effective at causing enantiomeric discrimination in the spectra of water-soluble cationic and anionic compounds with pyridyl, phenyl, and bicyclic aromatic rings. Binding studies show that mono- and ortho-substituted phenyl rings associate within the cavity of the calix[4]resorcinarenes, as do naphthyl rings with mono-, 2,3-, and 1,8-substitution patterns. Anthracene derivatives with an amino or sulfonyl group at the 1-position bind within the cavity, as well. Aromatic resonances of the substrates exhibit substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcinarene. The effectiveness of the reagents at producing chiral recognition in 1H NMR spectra is demonstrated with sodium mandelate, the sodium salt of tryptophan, and doxylamine succinate. While no one reagent is consistently the most effective, the calix[4]resorcinarenes with trans-4-hydroxyproline and trans-3-hydroxyproline moieties generally produce the largest nonequivalence in the 1H NMR spectra of the substrates.

Topics: Calixarenes; Hydroxyproline; Indicators and Reagents; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Phenols; Phenylalanine; Reference Standards; Solubility; Solvents; Stereoisomerism; Water

The complex formation of a tetraammonium C1-resorcinarene (R+4HCl) was studied using electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Although R+4HCl easily loses its counter ions in the ESI process, a neutral self-assembled structure with an intramolecular circular hydrogen-bonded 16-membered -N(+)-H ... X(-) ... H-N(+)- array with ammonium ion as the charge-giving species was observed in the gas phase. In addition to chloride, several other counter ions were also studied. The size and basicity of the counter ion as well as the size of the charge-giving cation strongly affected the gas-phase stability of the self-assembled system. H/D exchange experiments showed that the ammonium substituents in the apical position of R affect the hydrogen-bonding system in the resorcinarene. The complexation of the saturated dicarboxylic acids was found to depend on the length of the carbon chain. The rigidity of the molecular skeleton of the acid improved the complexation considerably. The orientation and position of the carboxylic groups also had an effect on the complexation and consequently enabled stereochemical differentiation of the acids. Mass spectrometric observations were supported by theoretical calculations.

Topics: Benzylamines; Bridged-Ring Compounds; Calixarenes; Cyclotrons; Data Interpretation, Statistical; Dicarboxylic Acids; Indicators and Reagents; Models, Molecular; Phenylalanine; Solvents; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared

The noncovalent complexation of tetraethyl and tetraphenyl resorcinarenes with mono-, di-, and oligosaccharides was studied with negative-polarization electrospray ionization quadrupole ion trap and electrospray ionization Fourier-transform ion cyclotron resonance mass-spectrometric analysis. The saccharides formed 1:1 complexes with deprotonated resorcinarenes, which exhibited clear size and structure selectivity in their complexation. In the case of the monosaccharides, hexoses formed much more abundant and kinetically stable complexes than pentoses or deoxyhexoses. A comparison of the mono-, di-, and oligosaccharides revealed that both the relative abundance and stability of the complexes increase up to biose and triose, but start to decrease after that point, as the length of the oligosaccharide is increased. This behavior was rationalized by comparing the lowest-energy conformations of the complexes formed between the resorcinarene and oligosaccharides. This comparison was achieved by using theoretical calculations and X-ray crystal studies.

Topics: Calixarenes; Carbohydrate Conformation; Carbohydrates; Cellobiose; Crystallography, X-Ray; Gases; Kinetics; Mass Spectrometry; Models, Molecular; Phenylalanine; Substrate Specificity

The spectroscopic properties of a chiral boronic acid based resorcinarene macrocycle employed for chiral analysis were investigated. Specifically, the emission and excitation characteristics of tetraarylboronate resorcinarene macrocycle (TBRM) and its quantum yield were evaluated. The chiral selector TBRM was investigated as a chiral reagent for the enantiomeric discrimination of amino acids using steady-state fluorescence spectroscopy. Chiral recognition of amino acids in the presence of the macrocycle was based on diastereomeric complexes. Results demonstrated that TBRM had better chiral discrimination ability for lysine as compared to the other amino acids. Partial least squares regression modeling (PLS-1) of spectral data for macrocycle-lysine guest-host complexes was used to correlate the changes in the fluorescence emission for a set of calibration samples consisting of TBRM in the presence of varying enantiomeric compositions of lysine. In addition, validation studies were performed using an independently prepared set of samples with different enantiomeric compositions of lysine. The results of multivariate regression modeling indicated good prediction ability of lysine, which was confirmed by a root mean square percent relative error (RMS%RE) of 5.8%.

Topics: Amino Acids; Calixarenes; Models, Molecular; Molecular Conformation; Phenylalanine; Quantum Theory; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet

Topics: Calixarenes; Chloroform; Dimerization; Heterocyclic Compounds, 4 or More Rings; Hydrogen Bonding; Macrocyclic Compounds; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine; Reference Standards; Sensitivity and Specificity; Stereoisomerism

Topics: Calixarenes; Fluorescence Resonance Energy Transfer; Models, Molecular; Molecular Structure; Phenylalanine

Nonylresorcinarene, in contrast to methylresorcinarene and nonylpyrogallene, exists in three isolable phases: a layer structure, a hexamer and an amorphous phase; the three are in thermal equilibrium.

Topics: Amination; Bromides; Calixarenes; Molecular Structure; Phenylalanine

Prolyl-bearing amphiphilic resorcinarenes, e.g. tetrakis(N-methylprolyl)tetraundecylcalix[4]resorcinarene, self-assemble as stable solid lipid nanoparticles; these fully characterized systems could be further functionalized at their surface with proteins, and interact with specific antibodies bound on a sensor surface.

Topics: Calixarenes; Drug Delivery Systems; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Phenylalanine; Serum Albumin, Bovine

The mechanisms of interactions between calix[4]resorcinarene and dopamine in monolayers formed at the air-water interface were studied by analyzing their mechanical, thermodynamic, and electrical properties evaluated from measurements of pressure-area isotherms and Maxwell displacement currents (MDCs). An increased concentration of dopamine in the water subphase resulted in an increase in the area per calix[4]resorcinarene molecule, an increase in the collapse pressure, and a shift in the monolayer phase transitions from the gaseous to the liquid state and from the liquid to the solid state toward higher molecular areas. A contactless method of recording MDCs enabled the monitoring of changes in the charge state of the monolayer-constituting molecules and the determination of a relationship between the phase state of the monolayer and the structural transitions of calix[4]resorcinarene. The changes of the MDC recordings started already in the gaseous state of the monolayer. On the basis of MDC values, we determined the normal component of the dipole moment of calix[4]resorcinarene, as well as that of its complex with dopamine. The dipole moment reached a maximum value of 1040 mD in the region of the phase transition from the liquid to the solid state of the monolayer. The results obtained suggest that the binding of dopamine with calix[4]resorcinarene depends on the orientation of the calixarene molecules in the monolayer. The calix[4]resorcinarene-dopamine interactions were also quantified in terms of the excess of Gibbs free energy, thereby allowing the evaluation of the energy of the calix [4]resorcinarene-dopamine bond, which was in the range from 1.95 to 8.54 kJ/mol depending on the surface pressure. This value implies weak interactions between these molecules.

Topics: Calixarenes; Dopamine; Electrochemistry; Phenols; Phenylalanine; Pressure; Surface Properties; Thermodynamics

A cyclophane-based resorcinarene trimer (3) bearing a dansyl moiety as an environmentally sensitive fluorophore was prepared by stepwise condensation of a tetraaza[6.1.6.1]paracyclophane skeleton with a dansyl moiety and three resorcinarene derivatives having heptacarboxylic acid residues in this sequence. The dansyl-appended cyclophane exhibited the following fluorescence properties regarding solvent polarity dependency and histone surface recognition: With increasing dioxane contents in dioxane/water solvents, the fluorescence intensity originating from the dansyl moiety of 3 increased along with a concomitant blue shift of the fluorescence maximum (lambdaem). The microenvironmentally sensitive fluorescence properties of dansyl fluorophore were maintained, even when the dansyl moiety was covalently attached to a cyclophane. Most interestingly, the cyclophane-based resorcinarene trimer exhibited recognition and fluorescence sensing capabilities toward histone, a small basic protein of eukaryotic chromatins. The fluorescence intensity originating from 3 increased along with a concomitant blue shift of lambdaem upon the addition of histone, reflecting the formation of 3-histone complexes. A relatively large fluorescence polarization (P) value was obtained for the 3-histone complexes (0.15), reflecting highly restricted conformations of 3, and the obtained P value was much larger than that of 3 alone in aqueous medium (0.07). The binding constant (K) of 3 with histone (unit basis) was estimated to be 2.1 x 106 M-1. On the other hand, upon the addition of acetylated histone (Ac-histone) to an aqueous solution containing 3, the extent of change in fluorescence intensity originating from the dansyl group of 3 was almost negligible, indicating that the electrostatic interactions between 3 and Ac-histone were weak. In addition, the fluorescence spectral changes were also small or negligible upon the addition of other proteins such as albumin, ovalbumin, peanut agglutinin, myoglobin, concanavalin A, cytochrome c, and lysozyme, having isoelectric points of 4.7, 4.8, 5.7-6.7, 6.8, 7.1, 9, and 11.0, respectively, to an aqueous solution containing 3.

Topics: Aza Compounds; Calixarenes; Dimerization; Ethers, Cyclic; Fluorescence; Histones; Macrocyclic Compounds; Models, Chemical; Molecular Conformation; Phenylalanine; Sensitivity and Specificity; Surface Properties; Time Factors

Dendron conjugated branches of stilbene and 4-styrylstilbene groups have been attached to resor-cinarene cores. A noticeable effect in solution for all dendrimers was observed in the fluorescence quantum yield. The optical properties do not change with concentration in solution. The optical properties of thin films are identical to those of the solutions indicating the absence of intermolecular interactions. The dendrimers were characterized by 1H, 13C NMR, FTIR, UV-Vis, fluorescence spectroscopy, MALDI-TOF or FAB+ mass spectrometry, and elemental analysis.

Topics: Calixarenes; Crystallization; Dendrimers; Fluorescent Dyes; Macromolecular Substances; Materials Testing; Microscopy, Fluorescence; Molecular Conformation; Nanostructures; Nanotechnology; Particle Size; Phenylalanine; Stilbenes; Surface Properties

The synthesis and X-ray crystal structures of the first resorcin[4]arene cavitands by ring-closing metathesis reaction are described.

Topics: Calixarenes; Crystallization; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine; Spectrometry, Mass, Electrospray Ionization

Citrate-capped gold nanoparticles (NPs) in aqueous solution were transferred directly into the organic solution mesitylene containing C-undecylcalix[4]-resorcinarene (C11-resorcinarene). C11-resorcinarene, which has long hydrophobic tails and phenolic hydroxyl groups, acted as both a phase-transfer and a capping agent. The C11-resorcinarene-capped gold particles could be isolated and dispersed in different organic solvents. Optical absorption spectra corresponding to surface plasmon resonance provided a broad band centered at 534 nm for C11-resorcinarene-capped gold NPs in mesitylene. High-resolution transmission electron micrograph images revealed that the average particle diameter of C11-resorcinarene-capped gold NPs is approximately 12 nm.

Topics: Calixarenes; Gold; Metal Nanoparticles; Particle Size; Phenylalanine; Solvents; Spectrum Analysis; Surface Plasmon Resonance; Water

Three new covalently linked molecular capsules were synthesized from their resorcinarene cavitand precursors in good yields. The capsules undergo reversible conformational switching between the closed "vase" form and the open "kite" form upon temperature or pH variation. The kite conformation obtained via either method in CDCl(3) switches to vase conformation upon addition of polar solvents such as acetone-d(6) or THF-d(8).

Topics: Calixarenes; Capsules; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Molecular Conformation; Phenylalanine; Solvents; Temperature

Topics: Allosteric Site; Calixarenes; Gases; Kinetics; Models, Molecular; Molecular Structure; Phenylalanine; Stereoisomerism; Valine

The assembly of C-methyl resorcinarene into a tubular supramolecular solid-state structure, its thermal stability, and its hosting properties are reported. Careful control of the crystallisation conditions of C-methyl resorcinarene and 1,4-dimethyl-1,4-diazoniabicyclo[2.2.2]octane (1,4-dimethyl DABCO) dibromide leads to a formation of two crystallographically different, but structurally very similar, solid-state nanotube structures. These structures undergo a remarkable variety of supramolecular interactions, which lead to the formation of 0.5 nm diameter nonpolar tubes through the crystal lattice. The formation of these tubes is templated by suitably sized small alcohols, namely, n-propanol, 2-propanol, or n-butanol. The self-assembly involves close pi...pi interactions between the adjacent resorcinarenes, and C--H...pi and cation...pi interactions between the resorcinarenes and the guest 1,4-dimethyl DABCO dications. The crystals of these supramolecular tube structures are thermally very stable and the included solvent alcohol can be removed from the tubes without breaking the single-crystalline structure of the assembly. After removal of the solvent molecules the tubes can be filled with other small, less polar solvent molecules such as dichloromethane.

Topics: Calixarenes; Crystallization; Hot Temperature; Molecular Conformation; Nanotubes; Phenylalanine; Piperazines; Solvents

Self-assembled capsules are hosts that recognize and surround smaller molecule guests of appropriate size, shape, and chemical surfaces. The space available inside is a cage of fixed solvent molecules, many of which are aromatic. These aromatics provide anisotropic shielding to guests, and a map of induced magnetic shielding for the inner space can be obtained through nucleus-independent chemical shift calculations. Experimental values of the magnetic environment can be determined by NMR spectra of the guests inside. We describe here the environment in a cylindrical capsule with tapered ends. A series of terminal acetylenes -- the narrowest of organic structures -- was synthesized and used to probe the magnetic shielding of the capsule's ends. Their NMR spectra showed that the acetylenic hydrogen experiences deshielding as it is forced deeper into the tapered end of the capsule where four benzene rings converge. Modeling and density functional theory calculations provided excellent agreement with the experimental values and established a molecular ruler to explore steric and magnetic environments inside the capsule.

Topics: Acetylene; Calixarenes; Hydrogen; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Phenylalanine

[reaction: see text] This research was undertaken to explore the interior surface of a synthetic receptor 1.1 with arylpyridines as guests. The interior surface differentiates the guests through the recognition of their nitrogen atoms. Experimental and computational analyses revealed that there is a delicate balance of attractions and repulsions between the host and the lone pairs of guests.

Topics: Calixarenes; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Molecular Structure; Nitrogen; Phenylalanine; Pyridines

The host-guest complexes of resorcin[4]arenes with small molecules in organic solutions are examined using modern NMR spectroscopic methods. The complexation of glutaric acid and beta-methyl d-glucopyranoside in chloroform were investigated through 2D COSY, 2D NOESY, 1D NOE, and diffusion-ordered NMR spectroscopy (DOSY) techniques. These methods indicate that the complex is a self-assembled capsule composed of six resorcinarenes that surround six guest molecules of glutaric acid or three molecules of beta-methyl d-glucopyranoside inside. The multiplicity of guest proton signals shows that the capsule provides an asymmetric magnetic environment that persists on the (1)H NMR time scale. The encapsulation of these guests and common solvents suggests that the phenomenon of reversible encapsulation in chemistry may be a century old.

Topics: Calixarenes; Glutarates; Models, Molecular; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phenylalanine; Solvents

We have studied the physical properties of monolayers formed by calix[4]resorcinarene and in mixtures with dipalmitoyl phosphatidylcholine (DPPC) in various molar ratios formed at the air-water interface and at presence of dopamine in water subphase by means of measurements of surface pressure and dipole potential. We showed that both calix[4]resorcinarene as well as its mixture with DPPC form stable monolayers at the water subphase. The presence of dopamine resulted in an increase of the mean molecular area and in a decrease of the compressibility modulus of the monolayers. For mixed monolayers at higher content of calix[4]resorcinarene (> 0.2 molar fraction) a deviation from ideal miscibility took place especially for monolayers in a solid state. This can be connected with formation of aggregates of calix[4] resorcinarene. Lowest miscibility and weakest interaction of dopamine with a monolayer was observed for calix[4]resorcinarene molar fraction of 0.33 in the monolayer.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Adsorption; Air; Calixarenes; Dopamine; Phenols; Phenylalanine; Surface Properties; Water

The host-guest complexes of resorcinarenes are re-examined in solution through modern spectroscopic methods; the assemblies are characterized by 1H NMR and the guest exchange rates are measured by EXSY NMR spectroscopy.

Topics: Calixarenes; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Phenylalanine

The molecular recognition of neurotransmitters, dopamine and acetylcholine with an amphiphilic resorcinarene receptor was investigated in an aqueous sodium dodecylsulfate (SDS) micelle system by 1H NMR measurements. The interaction distances of these neurotransmitters from the hydrophilic cavity of the amphiphilic receptor were estimated based on the calculation of the ring current shift using the atomic coordinates obtained from molecular dynamics calculation.

Topics: Acetylcholine; Calixarenes; Dopamine; Magnetic Resonance Spectroscopy; Micelles; Models, Molecular; Molecular Structure; Phenylalanine; Reference Standards; Sodium Dodecyl Sulfate; Structure-Activity Relationship; Water

Anion binding has been achieved with a resorcinarene substituted with four 2,2'-dipicolylamine moieties on the upper rim. The four dipicolylamine groups reside in proximity on one rim of the cavitand. The dipicolylamine groups were protonated with triflic acid to provide the cationic ammonium sites for anion binding. This anion receptor binds strongly to anions of different geometries, such as H(2)PO(4)(-), Cl(-), F(-), CH(3)CO(2)(-), HSO(4)(-), and NO(3)(-). The association constants for binding these anions are large, on the order of log K = 5 in CD(3)CN, a solvent of intermediate dielectric constant. These values represent significant binding compared to other cavitands with nitrogen pendant groups. Evidence suggests that the cavitand provides two identical receptor sites formed by two dipicolylamine groups, facilitating the simultaneous binding of two anions. Intramolecular binding of anions between two protonated dipicolylamine groups is indicated on the basis of the comparison to a structurally similar monomeric analogue and by semiempirical PM3 molecular modeling. Titrations with the analogue result in much weaker anion association, even at high concentrations, indicating the importance of proximity and preorganization of sites on the cavitand upper rim.

Topics: Algorithms; Anions; Binding Sites; Calixarenes; Ethers, Cyclic; Models, Molecular; Molecular Conformation; Molecular Structure; Phenylalanine; Picolines; Resorcinols

Biosensors based on natural ion channels combine a biological recognition mechanism with a physical transduction technique in a very selective and sensitive manner. This kind of molecular sensor will contribute to drug screening and environmental screening. Key information about channel gating, ion transport, and molecular mechanism is provided by the patch-clamp technique, commonly used for electrophysiological analysis. Here we report the synthesis of light-gated artificial ion channels, necessary constituents for construction of biosensors based on natural ion channels. The artificial gated ion channels described here are based on calix[4]resorcinarene. Opening and closing of the artificial ion channel is achieved by azo groups, which work like a lid. Azo groups alter their conformation on irradiation with light, and are chemically quite stable. Addition of a gate function will enhance the potential of synthetic channels to be used in sensors as molecular switches.

Topics: Azo Compounds; Biosensing Techniques; Calixarenes; Dimerization; Gramicidin; Ion Channel Gating; Ion Channels; Lipid Bilayers; Models, Biological; Phenylalanine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

A versatile, scaleable, one step synthesis of a lower rim mono-functionalized resorcinarene is described.

Topics: Calixarenes; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Phenylalanine

A novel silica-bonded stationary phase containing a functionalized resorcinarene selector was prepared by a straightforward synthesis. The complete modification of all resorcinic hydroxyl groups was achieved by reaction with isopropyl isocyanate. The derivatized resorcinarene selector was subsequently immobilized via the four alkenyl chains containing a terminal double bond by a free radical-induced reaction on mercaptopropyl-functionalized silica. A comprehensive characterization of the resulting bonded stationary phase was carried out by solid state NMR, IR and elemental analysis. The resulting selector is defined as a "polar headed" reversed phase since the highly ordered polar carbamate groups of the new stationary phase are located, compared to conventional polar embedded stationary phases, at a greater distance from the silica surface. Thus a new concept is introduced in the field of polar modified reversed-phase HPLC. The properties of the novel stationary phase are demonstrated by comparison with commercially available reversed phases.

Topics: Anthracenes; Calixarenes; Chromatography, High Pressure Liquid; Isotopes; Naphthalenes; Nuclear Magnetic Resonance, Biomolecular; Phenol; Phenylalanine; Silicon; Silicon Dioxide; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared

A resorcinarene bearing four TEMPO units recognizes small molecules in solutions.

Topics: Calixarenes; Crystallography, X-Ray; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Free Radicals; Hydrogen Bonding; Models, Molecular; Molecular Structure; Phenylalanine; Spin Labels

Resorcinarene 1b forms a hexameric assembly in water-saturated CDCl(3) that encapsulates one tetraalkylammonium salt (2(+)Br(-)). The remaining space is occupied by coencapsulated solvent molecules. A maximum of three and minimum of one CHCl(3) molecule were found inside of capsules with tetrapropyl- and tetraheptylammonium bromide, respectively. The encapsulation of the salt is endothermic and entropically favored by the liberation of the solvent molecules. The stabilities of the encapsulation complexes and the rates of guest exchange decrease for larger cations. The higher activation barriers for in/out exchange of the larger guests suggest tight conformational restraints in the transition state. It is likely that complete dissociation of one resorcinarene molecule is necessary for the exchange of the alkylammonium salts.

Topics: Calixarenes; Chloroform; Crystallography, X-Ray; Kinetics; Molecular Structure; Phenylalanine; Quaternary Ammonium Compounds; Thermodynamics

Topics: Amino Acids, Aromatic; Calixarenes; Kinetics; Models, Chemical; Molecular Conformation; Phenylalanine; Stereoisomerism

Resorcinarenes (resorcinol-aldehyde tetramers) of appropriate structures have been shown to change the hydro- and oleophilicities of a variety of surfaces. The phenomenon results from attachment of the rim of the bowl-like molecules to hydrophilic surfaces. Hydrophobic (alkyl) and oleophobic (perfluoro alkyl) "legs" attached to the bowls then determine the immediate surface property. Amounts required to modify surfaces are only between 2 and 10 mg m(-2) treated, and there is evidence of multilayer formation. Penetration of surfaces by a variety of liquids has been studied and cannot easily be understood as a function of density, viscosity, or surface tension.

Topics: Absorption; Calixarenes; Crystallography, X-Ray; Ethanol; Gold; Hexanes; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Molecular Structure; Oils; Particle Size; Phenylalanine; Surface Properties; Water

The design, chemical synthesis, guest binding, and self-assembly of tureen-shaped container molecules is presented. With a large noncollapsible interior and five external binding sites, each superbowl container host is shown to bind up to nine guest molecules in well-defined locations.

Topics: Calixarenes; Crystallography, X-Ray; Drug Delivery Systems; Ethers, Cyclic; Hydrocarbons, Brominated; Hydrogen Bonding; Models, Molecular; Phenylalanine; Resorcinols

The detection of saccharides in biological media is of great current importance for the monitoring of disease states. We have previously reported that solutions of boronic acid-functionalized macrocycles form acyclic oligomeric materials in situ. The oligomers contain fluorescent xanthene moieties. Current efforts are aimed at modulating the spectroscopic responses of these materials for the analysis of specific sugars. We describe conditions whereby the xanthene boronic acids exhibit high colorimetric fructose selectivity. In contrast, at physiological levels selective glucose monitoring can be achieved via fluorescence. Additionally, we describe a method which exhibits promise for detecting both glucose and fructose at dual wavelengths in the UV-Vis region. Mechanistic rationale for each of these findings is presented.

Topics: Blood Glucose; Boronic Acids; Calixarenes; Fluorescent Dyes; Fructose; Glucose; Humans; Macrocyclic Compounds; Molecular Structure; Monitoring, Physiologic; Phenylalanine; Spectrometry, Fluorescence; Spectrophotometry; Spectrophotometry, Ultraviolet; Xanthenes

Five acidic calix[4]arenes with carboxylic or sulfonic groups at either the upper or lower rim of the cavity and one resorc[4]arene were investigated to separate three thioxanthenes (flupentixol, clopenthixol, chlorprothixene) and a dibenz[b,e]oxepin derivative (doxepin) with cis-/trans-isomerism by nonaqueous capillary electrophoresis (NACE). Partial filling of the capillary with the UV-absorbing selectors led to a low detection limit and an advantageous signal-to-noise ratio (S/N). A sufficient electrophoretic mobility of the calixarenes towards the anode was necessary to outweigh the oppositely directed electroosmotic flow (EOF). This depended from the functional groups, the dissociation and the hydrodynamic radius of the cyclophanes. In contrast, the resorcinarene was useable only by addition of sodium dodecyl sulfate (SDS) because only the complex of the two selectors had an anodic apparent electrophoretic mobility. p-Sulfonyl-calix[4]arene (ss-a1) was the most capable selector for all E/Z-isomers with maximal alpha-values ranging from 1.056 for doxepin to 1.224 for chlorprothixene. This was due to the sufficient migration in reversed direction to the EOF even at low pH* values of 3.0. Otherwise, electrostatic as well as hydrophobic interactions with the positively charged isomers seem to contribute to a superior recognition. Increasing the concentration up to 15 mM ss-a1 and using acidic media (pH* 5.0) led to high separation efficiency. Changing the organic solvent provides a powerful tool to improve selectivity with N,N-dimethylformamide-methanol (DMF-MeOH)-mixtures for thioxanthenes. Further electrophoretic parameters were optimized, such as the concentration of the electrolytes, the addition of SDS, the kind of electrolytes and the voltage. Distinct differences in selectivities were found between the derivatives with thioxanthene and dibenzo[b,e]oxepin ring system, respectively. Further, the different basic side chain was responsible for the different selectivity at higher pH* values. In contrast, the substitution at position 2 of the thioxanthenes played a secondary role. Based on the studies of single parameters a method for a simultaneous separation of the four pairs of isomers within 13 min was developed.

Topics: Calixarenes; Dibenzoxepins; Electrolytes; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Isomerism; Osmolar Concentration; Phenylalanine; Polycyclic Compounds; Sodium Dodecyl Sulfate; Solvents; Thioxanthenes

Both a resorcinarene with pendant L-valine diamide groups (used as hydrogen-bonding selector) and a permethylated beta-cyclodextrin (used as inclusion-type selector) were chemically bonded to poly(hydromethyl)dimethylsiloxane in a one-pot reaction via Pt-catalyzed alkene hydrosilylation. This novel mixed chiral stationary phase (mixCSP) named Chirasil-Calixval-Dex resembles a combination of the known chiral stationary phases (CSPs) Chirasil-Calixval and Chirasil-Dex and it was used successfully in enantioselective gas chromatography toward a unified enantioselective GC separation system. It is demonstrated that Chirasil-Calixval-Dex retains the individual enantioselectivites of the single components. Thus the enantiomers of apolar hydrocarbons as well as polar amino acid derivatives can be separated with the mixed CSP.

Topics: beta-Cyclodextrins; Calixarenes; Chromatography, Gas; Cyclodextrins; Hydrogen Bonding; Phenylalanine; Siloxanes; Stereoisomerism

New HPLC phases with supramolecular selectors on the basis of calixarenes and resorcinarenes were investigated for the first time by means of empirically based test mixtures. The tests, originally developed for common reversed phases, were chosen to evaluate fundamental chromatographic properties of the new materials. In the first part of these studies three descriptors (hydrophobic retention capacity--k'(hyd), hydrophobic selectivity--alpha(hyd), steric selectivity--alpha(ster)) were determined. Except of higher alpha(ster) values and alpha(hyd) values with some methods for the resorcinarene phase the phases with supramolecular selectors were classified as less hydrophobic possessing lower hydrophobic and steric selectivities compared to three RP-C18 phases and a p-tert-butyl phenyl ether phase. The results were confirmed by means of a separation of geometric isomers of thioxanthenes. In contrast, in spite of lower k'(hyd) and alpha(hyd) values calixarene phases were more selective than the Kromasil-C18 phase in the separation of gestagenic and androgenic steroids due to specific interactions with the steroids of similar lipophilicity.

Topics: Calixarenes; Chromatography, High Pressure Liquid; Phenylalanine; Polycyclic Compounds

Topics: Calixarenes; Chromatography, High Pressure Liquid; Indicators and Reagents; Pharmaceutical Preparations; Phenylalanine; Stereoisomerism; Ultrasonics

[structure: see text] NMR diffusion measurements were used to probe the role of water molecules in a resorcinarene capsule in a CDCl(3) solution. It was found that the water/resorcinarene ratio affects both the chemical shift and the diffusion coefficient of the water molecules. From the NMR diffusion measurements we could conclude that the major species in the chloroform solution is the hexamer having eight water molecules that are in fast exchange, on the NMR time scale, with the bulk water.

Topics: Calixarenes; Chlorine Compounds; Diffusion; Logistic Models; Magnetic Resonance Spectroscopy; Molecular Structure; Phenylalanine; Solutions; Solvents; Water

A resorcin[6]arene with an r-trans-cis-trans-cis-trans configuration of the pendant ethyl groups forms tubular crystal structures.

Topics: Calixarenes; Molecular Structure; Phenylalanine

The chromatographic behavior of six calix[n]arene phases (n=4, 6, 8) and one calix[4]resorcinarene phase is described for the separation of cis- and trans-isomers of three thioxanthene (flupentixol, clopenthixol, chlorprothixene) and one benz[b,e]oxepin derivative (doxepin). The influences of two different organic modifiers (MeOH, MeCN) for the separation of the isomers on every column are described. Different selectivities of the stationary phases exist as a function of the ring size of the calixarenes and their substitution at the "upper rim" with p-tert.-butyl groups. Furthermore, the influence of free phenol groups on the resorcinarene phase is discussed. Relations between structural elements of the analytes and the retention behavior on the stationary phases are found. The selectivity of the calixarene and resorcinarene stationary phases is compared with a RP-C18 phase containing the same base silica. Advantages of the resorcinarene as well as of the calixarene columns exist for the separation of cis- and trans-isomers of three compounds dependent from the substitution in position 2 of the thioxanthenes, respectively the kind of the basic side chain of all substances.

Topics: Calixarenes; Chlorprothixene; Chromatography, High Pressure Liquid; Clopenthixol; Dibenzoxepins; Doxepin; Flupenthixol; Hydrogen-Ion Concentration; Indicators and Reagents; Isomerism; Macromolecular Substances; Phenylalanine; Thioxanthenes

Raman signal enhancements in excess of 10(7) can be achieved at near-infrared wavelengths when mid-nanometer sized gold particles self-organize into close-packed planar arrays. These substrates generate stable surface-enhanced Raman scattering which changes dramatically as a function of periodic structure and excitation wavelength.

Topics: Calixarenes; Electromagnetic Fields; Gold; Metal Nanoparticles; Nitrobenzenes; Phenylalanine; Spectrum Analysis, Raman; Temperature

A variety of aromatic guest molecules are co-encapsulated with Bu4SbBr in an assembly of six resorcinarene subunits.

Topics: Antimony; Calixarenes; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Organometallic Compounds; Phenylalanine

A kinetically stable, dimeric capsule is formed by tetrahydroxyresorcinarene in methanol; it encapsulates tropylium and tetramethylammonium cations.

Topics: Calixarenes; Capsules; Crystallography, X-Ray; Hydrogen Bonding; Molecular Structure; Phenylalanine; Solvents; Static Electricity; Water