Fourfold [2]rotaxanes based on calix[4]arenes

Tetraurea calix[4]arenes with four loops form exclusively heterodimers with open-chain urea calix[4]arenes when they are dissolved in aprotic solvents. These assemblies can be considered as pseudorotaxanes. If open-chain tetraureas ending with maleic imide functions are used, their Diels-Alder reaction with 1,4,5,8-tetrapentoxyanthracene leads to tetra[2]rotaxanes which cannot be split into the single calixarene parts by hydrogen bond breaking solvents.     

Encapsulated guest molecules in the dimer of octahydroxypyridine[4]arene

Recently a new type of calix[4]arenes has been synthesized via condensation of 2,6-dihydroxypyridine and a number of aldehydes. This type of pyridine[4]arenes forms capsules consisting of two single pyridine[4]arenes. These capsules can incorporate different guest molecules, like carboxylic acids and amides in this case. We proved that the guest acids really are incorporated inside the cavity of the capsules by electrospray mass spectrometry, NMR spectroscopy, and theoretical calculations.     

Self-sorting dimerization of tetraurea calix[4]arenes

Calix[4]arenes substituted by four urea functions are self-complementary molecules that spontaneously combine in apolar solvents in the presence of an ammonium salt to form dimeric capsules held together by a belt of hydrogen bonds. In the presence of tetraethylammonium salts, the Et4N+ cation is included as a guest. The sorting between dimeric capsules formed in a mixture of calix[4]arenes directly depends on the steric crowding of the substituents grafted on the urea groups whether aromatic derivatives or aliphatic chains linking urea functions in mono-, di-, or tetraloop structures. Simple rules allow one to anticipate which capsules will be exclusively formed when calix[4]arenes are mixed in different proportions. The stabilization of the dimeric structures by hydrogen bonds is thwarted by the overlaps of aliphatic loops and/or by bulky groups that cannot pass through these loops. Despite the structural similarity of the calixarenes, the exclusive formation of dimers of well-defined compositions and clear titration breaks are observed by electrospray mass spectrometry. This technique yields reliable information on stoichiometries and composition despite measurements in the gas phase rather than in solution and it does not suffer from excessive peak overlaps in contrast with NMR.     

Dimeric Capsules Formed by Tetra‐CMPO Derivatives of (Thia)Calix[4]arenes

Thiacalix[4]arene 2 , calix[4]arene 3 a and its tetraether fixed in the cone conformation 3 b form homo‐ and heterodimeric capsules in apolar solvents, which are held together by a seam of NH???O=P hydrogen bonds between carbamoylmethyl phospine oxide functions attached to their wide rim. Their internal volume of ～370 ų requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes (¹H‐ and ³¹P‐time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (ΔG=42.5 and 49.7 kJ mol^?1 for 3 a and 3 b ) than that for similar capsules of tetraurea calix[4]arenes 1 . Mixtures of 1 with 2 , 3 a , or 3 b contain only the two homodimers but the heterodimerization occurs with the tetraloop tetraurea 6 , which cannot form homodimers. Two dimers with cationic guests ( 2? (C₅H₅)₂Co⁺ ?2 and 3 a? Et₃NH⁺ ? H₂O ?3 a ) were confirmed by single‐crystal X‐ray analysis.     

Calix[4]arene-Based Triple-Stranded Metallohelicate in Water

The title complex is a triple-stranded metallohelicate organized by the self-assembly of 5,17-difunctionalized calix[4]arenes and metal cations with octahedral coordination geometry. Due to hydrophilic triethylene glycol chains on the lower rim of the calix[4]arene, the metallohelicate can encapsulate cationic guests in water. NMR and UV-vis titration experiments reveal that the metallohelicate captures a pyridinium guest with an alanine derivative to form a host-guest complex with a host-guest ratio of 1 : 1. CD spectroscopy confirms the bias of the P- and M-helical sense of the metallohelicate by the captured guest. The metallohelicate captures two molecules of dicationic N,N’-dimethyl-DABCO and monocationic N-methyl quinuclidine, exhibiting a positive allosteric effect. ¹H NMR titration experiments indicate that the bound guests are in close proximately to the aromatic rings of the ligands. Molecular mechanics calculations based on the UV-vis and NMR observations suggest that the first guest preorganizes the conformation of the metallohelicate to facilitate access of the second guest to the cavity.     

Wide rim urethanes derived from calix[4]arenes: synthesis and self-assembly

[reaction: see text] Calix[4]arenes 4, substituted at the wide rim by four N-tolyl-urethane groups, were synthesized, as well as derivatives 10a,b bearing two or three tolyl-urea groups beside of one or two urethane group(s). In contrast to tetra-tolyl urea 11, the urethane derivatives do not form hydrogen-bonded, dimeric capsules in CDCl3 or benzene-d6, but the dimerization can be induced for the triurea 10b by tetraethylammonium cations as guests. The quantitative formation of heterodimers is observed for all urethanes 4 and 10a,bin benzene-d6 in mixtures with a "tetra-loop" tetraurea 14, while "bisloop" tetraureas 13 require di- or triurea derivatives 10a,b for a clean heterodimerization.     

Self-assembled dendrimers with uniform structure

Calix[4]arenes substituted at their wide rim by four aryl urea residues (1) form hydrogen-bonded dimers in apolar solvents. Replacement of one urea residue by an acetamido moiety leads to calix[4]arene derivatives (5) which form hydrogen-bonded tetramers under the same conditions. Both self-assembly processes occur independently. Therefore, molecules have been prepared in which a tetra-urea calix[4]arene and a tri-urea mono acetamide derivative are covalently connected between their narrow rims by a long, mainly aliphatic chain [-O-(CH(2))(n)-C(O)-NH-(CH(2))(m)-O-] (7). In the presence of an equimolar amount of tetra-tosyl urea calix[4]arene () they form dendritic assemblies since the well known heterodimerization of tetra-tosyl and tetra-aryl urea calix[4]arenes prevents the formation of a cross-linked structure. Covalent connection of adjacent urea residues leads to tetra-loop derivatives (3) that cannot form homodimers, but instead form heterodimers with tetra-aryl or tetra-tosylureas. Therefore, similar dendrimers should be available using the selective dimerization observed for 3. The formation of a single, structurally uniform dendrimer from eight building blocks is confirmed by (1)H NMR spectra, showing only peaks that are also found for respective model assemblies. Translational diffusion coefficients of the assemblies have been determined using (1)H DOSY NMR.     

Water-soluble molecular capsules: self-assembly and binding properties

The self-assembly and characterization of water-soluble calix[4]arene-based molecular capsules (12) is reported. The assemblies are the result of ionic interactions between negatively charged calix[4]arenes 1 a and 1 b, functionalized at the upper rim with amino acid moieties, and a positively charged tetraamidiniumcalix[4]arene 2. The formation of the molecular capsules is studied by (1)H NMR spectroscopy, ESI mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC). A molecular docking protocol was used to identify potential guest molecules for the self-assembled capsule 1 a2. Experimental guest encapsulation studies indicate that capsule 1 a2 is an effective host for both charged (N-methylquinuclidinium cation) and neutral molecules (6-amino-2-methylquinoline) in water.     

Thermodynamics of sublimation of calix[4]arene complexes with solvent molecules

The inclusion of small neutral organic guests (C₆H₁₄, CH₂Cl₂, CH₃OH) by calix[4]arene receptors was found by ¹H NMR spectroscopy and microanalysis. The studied calix[4]arenes can form stable intramolecular complexes with solvent molecules which keep the stoichiometric composition without changing under conditions of the sublimation experiment. The saturated vapour pressures of calix[4]arenes and complexes of calix[4]arenes with solvent molecules were determinated for the first time by the Knudsen’s effusion method in the wide temperature range. The changing of standard thermodynamic parameters of complexation by transfer process from condensed state to vapour phase was estimated. It was shown that the large flexibility of the calixarene ligand structure corresponds to a strongly negative entropic contribution as well as negative enthalpy term to the Gibbs energy of formation of host–guest complexes in the gas phase.     

Self-assembly of molecular capsules in polar solvents

[structure: see text] We present a novel type of molecular capsule formed by self-organization of calix[4]arenes with several oppositely charged functional groups located at their upper rims. In highly polar solvents, the complementary half-spheres form stable 1:1 complexes with association constants of up to 7 x 10(5) M(-)(1) in methanol. The cavity inside the capsules is large enough for the inclusion of small aliphatic or (hetero)aromatic guest molecules.     

Do pentaurea calix[5]arenes form hydrogen bonded dimeric capsules?

Calix[5]arenes substituted at their wider rim by five urea residues do not form hydrogen bonded dimeric capsules in aprotic, apolar solvents, in contrast to their calix[4]arene analogs, although molecular dynamic simulations predict very similar geometrical parameters for both cases. The reason for this different behavior is most probably the higher energetic cost which must be paid to arrange the calix[5]arene skeleton in the C₅-symmetrical conformation required for the dimerization.     

Water‐Soluble Molecular Capsules: Self‐Assembly and Binding Properties

The self‐assembly and characterization of water‐soluble calix[4]arene‐based molecular capsules ( 1?2 ) is reported. The assemblies are the result of ionic interactions between negatively charged calix[4]arenes 1 a and 1 b , functionalized at the upper rim with amino acid moieties, and a positively charged tetraamidiniumcalix[4]arene 2 . The formation of the molecular capsules is studied by ¹H NMR spectroscopy, ESI mass spectrometry (ESI‐MS), and isothermal titration calorimetry (ITC). A molecular docking protocol was used to identify potential guest molecules for the self‐assembled capsule 1 a?2 . Experimental guest encapsulation studies indicate that capsule 1 a?2 is an effective host for both charged (N‐methylquinuclidinium cation) and neutral molecules (6‐amino‐2‐methylquinoline) in water.     

Capsule-like assemblies in polar solvents

Calix[4]arene derivatives with four anionic groups at their upper rim form discrete 1:1 complexes with complementary calix[4]arene derivatives bearing four cationic groups at their upper rim. Each cation is bound by two anions, and vice versa, in a mutual chelate arrangement, reinforced by a network of ionic hydrogen bonds. These multiple electrostatic interactions lead to the formation of highly stable capsule-like assemblies even in polar protic solvents such as methanol and water. In the capsule interior a cavity is formed that is in principle large enough for the encapsulation of small aliphatic and aromatic guests (170-230 A(3)). Monte Carlo simulations in water reproducibly lead to the same regular opimized structures. These differ mainly by their inner volume and flexibility, as demonstrated by molecular dynamics calculations. Most half-spheres can be synthesized by way of the tetrakis(chloromethyl) or the tetrabromocalix[4]arene intermediate. Oppositely charged calix[6]arenes also form strong complexes, but no indication was found for a lock in the cone conformation. The formation of the ball-shaped complexes from calix[4]arene building blocks was studied with Job plots, NMR titrations, NOESY, and variable-temperature experiments, as well as ESI-MS measurements. Investigations aimed at the inclusion of various guest molecules were carried out with alcohols, sulfoxides, benzene derivatives, and ammonium, as well as pyrazinium guests. Although binding isotherms were generated with cationic guests, these must be considered to be loosely associated around the seam rather than included inside the capsule.     

Exclusive self-assembly of a polar dimeric capsule between tetraurea calix[4]pyrrole and tetraurea calix[4]arene

The exclusive self-sorting observed in the self-assembly process between tetraurea benzyl calix[4]pyrroles and tetraurea tolyl calix[4]arene to afford unprecedented hybrid dimeric capsules with polar interiors is described. The coencapsulation of a solvent molecule with an organic guest yields four particle aggregates in which the guests are confined and restricted into single hemispheres due to the polar requirements of the internal cavity.     

Thermodynamic parameters of sublimation of calix[4]arenes

The temperature dependences of the vapor pressure of calix[4]arenes were determined by the Knudsen effusion method. Some calix[4]arenes can form congruently subliming intramolecular compounds with a solvent. The thermodynamic parameters of the sublimation of the compounds were calculated. Molecules of organic solvents incorporated in the cavity of calix[4]arenes stabilize the crystal lattice, increasing the enthalpy of sublimation. The electrostatic interactions presumably make a significant contribution to stabilization of the crystal lattice of stoichiometric complexes of calix[4]arenes with solvents.     

Guest-enhanced kinetic stability of hydrogen-bonded dimeric capsules of tetraurea Calix

Inclusion complexes of self-assembled molecular dimers composed of two tetratolylurea calix[4]arenes show strongly different kinetic stability for different guests. In cyclohexane-d(12), half-life times for the exchange of a guest against the solvent vary from 2.9 h (chloroform) through 20 h (benzene) and 74 h (fluorobenzene) to 78 days for cyclohexane. This demonstrates that the kinetic stability of such a dimer can be strongly increased by the choice of a suitable guest.     

Binding of inorganic cations by p-sulfonatocalix[4]arene monitored through competitive fluorophore displacement in aqueous solution

A new working principle for detecting inorganic cation binding by water-soluble calix[4]arenes involves the displacement of a fluorescent azoalkane as guest. Fluorescence regeneration is observed for various metal ions, and binding of monovalent cations (alkali and ammonium) to p-sulfonatocalix[4]arene is detected and quantified for the first time.     

Synthesis and self-assembly of thio derivatives of calix[4]arene on noble metal surfaces

Self-assembled monolayers (SAMs) provide a simple route to functionalize electrode surfaces with organic molecules. Herein we use cavity-containing derivatives of calix[4]arenes in SAMs. Bound to noble metal surface, the assembled molecules are candidates to serve as molecular sieves for H 2 molecules and H (+) ions, which could have relevance for fuel cell applications. Tetra- O-alkylated calix[4]arenes with thiolacetate and thiolamide wide-rim anchoring groups in cone and partial-cone conformations were designed, synthesized and self-assembled onto Au, Pt, and Pd surfaces. The resulting SAMs were systematically examined. Single crystal X-ray diffraction of 5,11,17,23-tetrakis(thioacetyl)-25,26,27,28-tetra- i-propoxycalix[4]arene confirmed the cone conformation and revealed the cavity dimensions of the SAMs that were formed by immersing noble metal substrates (Au, Pt and Pd deposited on Si-wafers) in solutions of calix[4]arenes. Surface characterization techniques including ellipsometry, cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) were used, indicating that the metal surface is terminated with a monomolecular layer. Experimental thicknesses obtained from the ellipsometry are consistent with the calculated values. CV results showed 50 to 80% physical passivation against the Fe(CN) 6 (3-/4-) couple, implying an overall relatively low concentration of defects and pinholes in the films. The binding energies of the S2p core level in the XPS were consistent with the literature values and revealed that up to 3.2 out of four anchoring groups were bonded to the noble metal surface.     

Self-assembled dimers with supramolecular chirality

The possibilities to form dimeric capsules with supramolecular chirality from tetraurea calix[4]arenes composed of two different phenolic urea units are discussed in general and demonstrated experimentally for various selected examples.     

Hydrogen bonded homo- and heterodimers of tetra urea derivatives of calix[4]arenes

Calix[4]arene ethers fixed in the cone conformation and substituted at the upper rim by various urea residues have been synthesized by reaction of the amino calix[4]arenes with isocyanates. Their dimerisation in apolar solvents has been established by the formation of mixed dimers consisting of two different urea derivatives.