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.     

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.     

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.     

New molecular topologies by fourfold metathesis reactions within a hydrogen-bonded calix[4]arene dimer

A calix[4]arene tetrapentyl ether in the cone conformation substituted at its wide rim by four m-(omega-octenyloxy)phenyl urea groups forms hydrogen-bonded dimeric capsules in dichloromethane/benzene (95:5). Metathesis reaction with Grubbs' catalyst under high-dilution conditions (1.1 x 10(-4) M) followed by hydrogenation leads to a covalent connection of all the urea groups within a dimer. Three topologically different products may be expected in such a reaction: a bis[2]catenane, a doubly bridged monocatenane and a tetrabridged capsule. All three possible reaction products could be isolated in an overall yield up to 60 % for the separated and purified compounds. Their identification was based on the NMR patterns which reflect the characteristic symmetry properties of the isomeric products especially in the region of the hydrogen-bonded NH protons and were further confirmed by MALDI-TOF mass spectra. Further structural support for the bis[2]catenane comes from a single-crystal X-ray structure, although severe disorder prevents the localization of all atoms in the aliphatic chains connecting the two calix[4]arenes. Kinetic studies for the guest release/exchange (cyclohexane against the solvent [D(6)]benzene) do not show remarkable differences between the starting dimer and the additionally linked dimers, while the mobility of an included tetraethylammonium cation is obviously more restricted.     

Hydrogen-bonded dimers of tetra-urea calix[4]arenes stable in THF

[structure: see text]. Whereas tetra-urea derivatives of tetra-alkoxy calix[4]arenes 1 exist as single molecules in THF, dimeric hydrogen-bonded capsules are exclusively found for the corresponding calix[4]arene derivatives 3 and 2 with two or four free hydroxyl groups. Comparison with the rigidified tetra-urea 5 suggests that this increased stability of the dimers is due to the stabilization of their four-fold symmetry by intramolecular hydrogen bonds between the phenolic hydroxyl groups.     

Highly selective synthesis of a 1,3,5-tris-protected calix[6]arene-type molecular platform through coordination and host-guest chemistry

An elegant methodology based on the synergistic combination of coordination and host-guest chemistry led to the highly efficient synthesis of a unique C(3v)-symmetrical, calix[6]arene-based molecular platform with three protected amino arms in alternating positions. The key step involves the formation of a stable supramolecular host-guest Zn(II) complex from a C(6v)-symmetrical calix[6]hexaamine. Indeed, in the presence of a polar neutral guest and a strong donor that acts as an exogenous ligand, three alternating amino groups of this calix[6]hexaamine are selectively coordinated to the Zn(II) ion while the three others remain free and are thus much more reactive toward chemical reagents. In addition to this protective role, the metal centre preorganises the C(3v)-symmetrical complex in such a way that the uncoordinated NH(2) groups are directed toward the outside of the cavity; they are then accessible for a chemical transformation. Hence, reaction of these alternating free amino groups with a protective reagent (i.e., Boc(2)O) followed by zinc decoordination quantitatively and selectively yielded the 1,3,5-tris-Boc-protected calixarene derivative on a gram scale. It was shown that the presence of all the partners of the key intermediate Zn complex (i.e., the metal centre, the exogenous ligand and the included guest) is crucial for a high selectivity. Finally, a two step sequence that led to a C(3v)-symmetrical 1,3,5-tris-acetylated calix[6]hexaamine through the removal of the Boc groups illustrates that the 1,3,5-tris-protected calix[6]hexaamine is a promising molecular platform. Examples of such readily available C(3v)-symmetrical calixarene-based building blocks are extremely rare in the literature.     

Tetraurea calix[4]arenes with sulfur functions: synthesis, dimerization to capsules, and self-assembly on gold

Various calix[4]arene derivatives, fixed in the cone conformation by decylether groups and functionalized at their wide rim by urea residues, were synthesized. In two compounds (,) sulfur functions were attached to the urea groups via different spacers in order to allow binding to metal surfaces. While they exist as single molecules in polar solvents, tetraurea calix[4]arenes of this type () combine to form dimeric capsules in aprotic, apolar solvents. A solvent molecule is usually included in such a capsule, if no guest with a higher affinity is present. In the presence of an equimolar amount of the tetratosylurea, the exclusive formation of heterodimers, consisting of one molecule of and, is observed. The homo- and heterodimerization of the newly prepared derivatives, were studied by 1H NMR to establish the conditions under which they exhibit the desired dimerization behaviour. Self-assembled monolayers (SAMs) were formed using the single calix[4]arenes, and the heterodimeric capsules. Chloroform, dichloromethane and ferrocenium cations were used as guests in these immobilized heterodimeric capsules. The particular supramolecular architecture of the heterodimers should ensure that, after the immobilization on the metal surface, decomposition of the capsules and release or exchange of the guest is impossible or at least hindered. The self-assembly process and the stability of SAMs formed by capsules filled with ferrocenium cations in electrolyte solutions were tested with surface plasmon spectroscopy. The inclusion of guests, such as dichloromethane or ferrocenium, in the immobilized capsules were confirmed by classical surface plasmon spectroscopy, by gold nanoparticle absorption spectroscopy and by time-of flight secondary ion mass spectrometry (ToF-SIMS). The film stability and quality was tested by cyclic voltammetry.     

Formation of ionic associates from oppositely charged calix[4]resorcinarene host molecules in the presence of guest molecules

The conditions for the formation and existence of capsular dimeric associates in a solution were studied. The associates are formed by the oppositely charged resorcinarene derivatives (tetrakis(dimethylaminomethyl)calix[4]resorcinarene hydrochloride and tetrakis(sulfonato- methyl)calix[4]resorcinarene). Possibilities of formation of a capsule in the presence of the molecules giving inclusion complexes with one of the macrocycles were considered. Switching between two states “capsular associate—mixture of original macrocycless” is achieved by controlling the ionic strength of the solution. The interaction of the host—guest complexes with complementary resorcinarene leads to capsular associate closure with the synchronous displacement of the guest molecules into the aqueous solution bulk.     

Compensation of steric demand by cation-pi interactions,cobaltocenium cations as guests in tetraurea calix[4]arene dimers

The affinities of ferrocene (2) and the cobaltocenium cation (3+), which have roughly the same size and differ in their charge, towards the inner cavity of the dimeric capsule formed by tetraurea calix[4]arene (1) were studied in C2D4Cl2 solutions. While 3+, which occupies more than 75% of the internal volume of the dimer, is readily encapsulated this is not the case for 2. This is probably due to cation-pi interactions, which operate only between 3+ and the aromatic rings of the calix[4]arene dimer. We found that the affinity of the cobaltocenium cation is higher than that of the tropylium cation (4+) and is only 2-3 times less than that of the tetraethylammoniun cation (5+). From the variable temperature 1H NMR spectra of this capsule, the free energy of activation at 298 K (deltaGdouble dagger(298K)) for the reorientation of the hydrogen bonded belt between the two parts of the dimer could be determined by total line shape analysis for the aromatic protons of the calixarene. The value of 14.3 +/- 0.2 kcal mol(-1) for the dimeric capsules of 3+ PF6- is very similar to the free activation energy found for dimeric capsules of 1 with 4+ PF6- and 5+ PF6- in C2D4Cl2. It becomes significantly lower, if PF6- is replaced by BF4-. We also found that ten times more DMSO is needed to disrupt the capsule 1 x 3+ x 1 than the corresponding 1 x 1 dimer containing benzene as guest. This demonstrates again the importance of the cation-pi interactions for the stability of such hydrogen-bonded dimeric capsules.     

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.     

Guest exchange in dimeric capsules of a tetraurea calix[4]arene in the solid state

A solid powder of hydrogen bonded dimers of a tetraurea calix[4]arene is able to exchange the encapsulated guest in contact with the vapor of a second guest. The molecules of a guest-free powder obtained from a polar solvent cannot rearrange in the solid phase to form new guest-filled capsules under these conditions.     

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.     

Hydrogen-bonded dimers of a thiacalixarene substituted by carbamoylmethylphosphineoxide groups at the wide rim

A thiacalix[4]arene derivative bearing four carbamoylmethylphosphineoxide groups at the wide rim forms hydrogen-bonded, dimeric capsules with S8 symmetry in the crystalline state and in apolar solvents, where the inclusion of cationic guests could be proved by 1H NMR and ESI mass spectra.     

Recognition of amides by new rigid Calix

The synthesis of new hosts specifically designed for the recognition of amides, characterized by two binding regions: a rigid calix[4]arene cavity and a sidearm, inserted at its rim, able to form strong hydrogen bonds, is described. The binding abilities of the new receptors toward amides of general structure R(1)CONR(2)R(3) have been investigated in CDCl(3) solution by (1)H NMR spectroscopy. When the additional binding site is the N-phenylureido group spaced by a methylene unit from the apolar cavity, binding constants up to 756 M(-)(1) were measured. Neither the two separate potential binding sites, nor the model host, where the calix[4]arene skeleton is flexible show detectable binding ability toward the series of guests examined. The rigidity of the calix[4]arene apolar cavity is the key control element in determining the efficiency of these molecular recognition processes. The presence of NH groups in the guest controls the efficiency and selectivity of binding.     

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.     

Calix[4]arene-based bis[2]catenanes: synthesis and chiral resolution

The exclusive formation of hydrogen-bonded dimers between tetraaryl and tetratosylurea calix[4]arenes has been used to prepare a series of ten "bisloop" tetraurea calix[4]arenes 3, in which adjacent phenylurea groups are covalently linked through alpha,omega-dioxyalkane chains. This dimerization with tetratosylurea 2 as template preorganizes the alkenyl residues of tetra(m-alkenyloxyphenyl) ureas 1 and enables their selective connection in high yield (up to 95 %) by olefin metathesis followed by hydrogenation. The "bisloop" calixarenes 3 also exclusively form heterodimers with 1. Thus, in a separated metathesis/hydrogenation sequence, a series of 14 cyclic bis[2]catenanes 4, in which two calix[4]arenes are connected through their wide rims by two pairs of interlocked rings (total size 29 to 41 atoms), were prepared in yields of up to 97 %. Optical resolution of these chiral bis[2]catenanes was studied by HPLC on chiral stationary phases. The single-crystal X-ray structure of one example (4(P,10)) confirmed the interlocking rings and revealed that the hydrogen-bonded dimeric capsule of the calix[4]arene can be "completely" opened.     

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.     

Linear all-ortho oligomers of phenol–formaldehyde resins. I. Preparations,characterizations, and solution properties

Three kinds of all-ortho methylene-linked phenolic oligomers, i.e., 4-tert-butylphenol (BP), phenol (AO), and O-methylated BP (BPM), were prepared with good yields and their dilute solution properties were studied. In acetone, all of these oligomers are highly solvated and molecularly dispersed. In chloroform, however, AO and BP molecules strongly form hydrogen bonds among themselves. By intramolecular and intermolecular hydrogen-bondings, a large portion of the dimers and the trimers of AO and BP associate to form bimolecular aggregates in chloroform, assuming pseudo-cyclic conformations analogous to calix [4] arene and calix [6] arene, respectively. By intramolecular hydrogen-bonding, the tetramers and the hexamers also form pseudo-cyclic conformations by themselves in chloroform. © 1993 John Wiley & Sons, Inc.     

Fourfold tetraurea calix[4]arenes--potential cores for the formation of self-assembled dendrimers

Wide rim tetraurea calix[4]arenes monofunctionalized at the narrow rim by COOH or NH2 have been synthesized in five steps from t-butylcalix[4]arene tripropylether. Their covalent linkage via the narrow rim to a central calix[4]arene fixed in the 1,3-alternate conformation led to pentacalix[4]arenes 9 bearing four tetraurea derivatives in the cone conformation in a flexible tetrahedral arrangement. Their self-assembly via the formation of hydrogen bonded dimeric capsules has been studied under different conditions. A fourfold heterodimerisation of tetrakis-tetraurea derivatives of type 9 with tetratosylurea 10 has been confirmed by 1H NMR-spectroscopy and dynamic light scattering.     

Dimeric molecular capsules under redox control

A new tetraferrocenylurea calix[4]arene was prepared in order to investigate its dimerization properties. 1H NMR spectroscopic data clearly established that this calixarene forms stable dimeric molecular capsules in chloroform solution. The dimeric capsules are stabilized by the formation of multiple hydrogen bonds between the urea functional groups on the calixarene upper rims. In the dimer, eight ferrocene groups are held in proximity to the "seam" of hydrogen bonds. Upon oxidation of the ferrocene residues, electrochemical, PGSE NMR, and IR spectroscopic data revealed that the hydrogen bonds are broken, leading to the dissociation of the dimeric molecular capsule.