Heterodimeric Capsules Research Articles

Moving systems of polar dimeric capsules out of thermal equilibrium by light irradiation.

Heterodimeric capsules self-assembled from tetraurea calix[4]pyrrole and tetraurea calix[4]arene provide unique molecular containers for the organised inclusion of small polar molecules. By inserting stimuli-responsive groups (azobenzene) in the heterocapsule structure, we are able to modify the equilibrium state of the system or the exchange between different host-guest assemblies in a reversible manner.

Formation of Heterodimeric Resorcin[4]arene Capsules on Surfaces: An X-Ray Photoelectron Spectroscopy Investigation

A perfect fit: Hydrogen bond formation of heterodimeric molecular capsules assembled from complementary functionalized resorcinarene cavitands is of considerable interest from the viewpoint of multicomponent molecular assemblies. The formation of hydrogen-bonded heterodimeric capsules AB (see picture) based on a monolayer of tetrapyridyl resorcinarenes B is verified by means of X-ray photoelectron spectroscopy analyzing N 1s signatures.

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

Thiacalix[4]arene 2, calix[4]arene 3a and its tetraether fixed in the cone conformation 3b form homo- and heterodimeric capsules in apolar solvents, which are held together by a seam of NH...O=P hydrogen bonds between carbamoylmethyl phosphine oxide functions attached to their wide rim. Their internal volume of approximately 370 A(3) requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes ((1)H- and (31)P-time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (DeltaG=42.5 and 49.7 kJ mol(-1) for 3a and 3b) than that for similar capsules of tetraurea calix[4]arenes 1. Mixtures of 1 with 2, 3a, or 3b contain only the two homodimers but the heterodimerization occurs with the tetraloop tetraurea 6, which cannot form homodimers. Two dimers with cationic guests (2.(C(5)H(5))(2)Co(+).2 and 3a.Et(3)NH(+).H(2)O.3a) were confirmed by single-crystal X-ray analysis.

Mechanism of Orientational Isomerism of Unsymmetrical Guests in a Heterodimeric Capsule: Analysis by Ab Initio Molecular Orbital Calculations

The geometries and interaction energies of the heterodimeric capsule [tetrakis(4-hydroxyhphenyl)-cavitand 1 and tetra(4-pyridyl)-cavitand 2] complexes with methyl p-acetoxybenzoate 3, methyl p-ethoxybenzeoate 4, and p-ethoxyiodobenzene 5 were studied by ab initio molecular orbital calculations. The optimized structures and charge distributions of the complexes suggest that the electrostatic interactions of oxygen atoms in the guest molecules with the hydrogen atoms of aromatic rings and methylene-bridge rim in the heterodimeric capsule stabilize the complexes. The calculated relative energies of the two orientational isomers of the complexes well reproduce the experimentally observed orientational selectivity of the guest molecules. The calculated stabilization energies for the major orientational isomers of the heterodimeric capsule (1.2) complexes with guest molecules (3, 4, and 5) are -21.6, -19.6, and -19.4 kcal/mol, respectively. Those for the minor orientational isomers are 1.5, 3.5, and 3.7 kcal/mol smaller (less negative), respectively. The magnitude of the calculated energy differences agrees well with the order of the experimental population of the major orientational isomer (3 < 4 approximately 5). The large electron correlation contributions to the attraction (-27.0 to -31.8 kcal/mol) show that the dispersion interactions are the major source of the attraction in the complexes, while the electrostatic interactions (-4.9 to -12.5 kcal/mol) are also an important source of the attraction. Although the electrostatic interactions are weaker than the dispersion interactions, the highly orientation dependent electrostatic interactions mainly determine the orientation of the unsymmetrical guest molecules in the complexes. The electrostatic interactions in the major orientational isomer are 2.6-3.9 kcal/mol larger (more negative) than those in the minor orientational isomer, while the differences of other energy terms are small (less than 1.1 kcal/mol). The interaction energies calculated for model complexes show that the CH/pi interactions are not playing important roles in controlling the orientation of the guest molecules in the complexes.

Efficient Self-Sorting of a Racemic Tetra-Urea Calix[4]Pyrrole into a Single Heterodimeric Capsule

A racemic calix[4]pyrrole self-sorts into a single achiral heterodimeric capsule. This process is induced either by encapsulation of one ditopic or two monotopic N-oxide guests. The influence of the guest structure in the dynamics of the disproportionation process of the two homochiral capsules is reported. The unidirectional sense of rotation of the urea groups assigned to the heterodimeric capsule is explained as the outcome of an induction of chirality from the stereogenic centers.

Single-molecule force spectroscopy of supramolecular heterodimeric capsules

The specific interaction of a supramolecular binding motif was quantitatively evaluated by dynamic single-molecule force spectroscopy (SMFS) using an atomic force microscope (AFM). The supramolecular capsule forms by two different cavitands stitched together by four hydrogen bonds between carboxylic acid and pyridyl groups. The tetra(carboxyl)cavitand is monofunctionalized at the lower rim with a flexible poly(ethylene glycol) linker and attached to the AFM sensor tip. Single-molecule association experiments are accomplished using a diluted self-assembled monolayer (SAM) of the tetra(pyridyl)cavitand on a gold substrate. The measured single-molecule dissociation forces of the heterodimeric capsule represent the mechanical stability of the supramolecular system and allow a quantitative evaluation of the interaction according to the Bell-Evans model yielding dissociation rate constant k(off) = (0.14 +/- 0.14) s(-1), reaction length x(beta) = (0.56 +/- 0.076) nm and an estimated value of DeltaG(0) = -27 kJ mol(-1).

Guest-encapsulation behavior in a self-assembled heterodimeric capsule

Tetra(4-pyridyl)-cavitand 1 and tetrakis(4-hydroxyphenyl)-cavitand 2 self-assemble into a heterodimeric capsule 1· 2 via four PhOH⋯pyridyl hydrogen bonds in CDCl 3, wherein one molecule of 1,4-disubstituted-benzene as a guest is encapsulated to form a ternary complex, guest@( 1· 2). The X-ray crystallographic analysis of (methyl p-ethoxybenzoate)@( 1· 2) confirmed that the methyl ester and ethoxy groups of the encapsulated guest are oriented to the cavity ends of the 1 and 2 units, respectively. The scope and limitation of guest encapsulation in 1· 2, including guest-binding selectivity and orientational isomeric selectivity, are described from the viewpoint of size complementarity and CH–π, CH–halogen, and halogen–π interactions between guest and the cavity of 1· 2.

Multiple catenanes based on tetraloop derivatives of calix[4]arenes

Four novel tetraarylurea calix[4]arenes ( 4a– d) have been synthesized, substituted by ω-alkenyloxy residues in 3,5-positions of the arylurea residues. The eight alkenyl groups were pairwise connected by olefin metathesis and subsequent hydrogenation. The ring-closure reaction was carried out with heterodimers exclusively formed by 4 with a tetratosylurea calix[4]arene 1, which serves as a template in this reaction step. The potential trans-cavity bridging is entirely suppressed in this way. Bis- and tetraloop calix[4]arenes cannot form dimers due to overlapping loops. However, they readily form heterodimers with open-chain tetraureas, as long as their urea residues can pass through the loops. Thus, five heterodimeric capsules 8a– e with bis[3]catenane structure were synthesized using again the olefin metathesis followed by hydrogenation. Two different strategies were compared for this reaction sequence, starting with heterodimers formed either by tetraloop derivatives 5 with tetraalkenyl tetraureas 6 (pathway A) or by bisloop derivatives 7 with octaalkenyl tetraureas 4 (pathway B). A distinct advantage of one of these pathways was not observed; the bis[3]catenanes were obtained with yields of 20–60%. Heterodimers formed by tetraloop derivatives 5b– d and octaalkenyl ureas 4b– d were converted analogous to three novel cyclic [8]catenanes 9a– c in 30–42% yield. The structure of the novel catenanes was unambiguously proved by 1H NMR and ESI MS, and for 8a and 9a additionally by single crystal X-ray analysis.

Electrochemical response of ferrocenium filled calix[4]arene capsules in solution and immobilized on gold

Hydrogen-bonded dimers of tetra-urea calix[4]arenes are able to include ferrocenium ions as a guest. Heterodimeric capsules are exclusively formed in 1:1 mixtures of tetra-arylurea calix[4]arene 1 with tetra-tosylurea calix[4]arene 2. Sulfide groups attached via spacers on the urea rim of 1 allow their binding to metal surfaces rendering simultaneously their dissociation more difficult. Thus, the electrochemical response of encapsulated ferrocenium could be studied in a self-assembled monolayer (SAM) in addition to the solution electrochemistry with cyclic voltammetry. The stability of the electrochemically active monolayers was tested after a heat treatment (225 °C for 30 min in N 2 atmosphere) and multiple cycling (up to 1200 cycles), which could be required for a possible application as molecular based information storage.

Heterodimeric capsules formed by tetratosyl and tetratolyl urea calix[4]arenes

Predictions made by MD simulations for size, shape and guest inclusion of a heterodimer formed by a tetratosyl and a tetratolyl urea calix[4]arene and for its hydrogen bonding system have been entirely confirmed by a single crystal X-ray structure.

Self-Assembled Polymers Based on bis-Tetra-Urea Calix[4]arenes Connected via the Wide Rim

Six double calixarenes were synthesised in which two tetra-urea calix[4]arenes are linked by a rigid spacer between the urea functions at their wide rim. The dimerisation of their tetra-urea parts leads to hydrogen-bonded polymeric assemblies in apolar solvents. The addition of the stoichiometric amount of a tetra-tosylurea calix[4]arene disrupts the polymeric structures due to the preferred formation of heterodimeric capsules between tetra-aryl and tetra-tosylurea calix[4]arenes. The existence of polymeric assemblies was further established by AFM studies on spin-coated samples.

Ion Pair-Driven Heterodimeric Capsule Based on Boronate Esterification: Construction and the Dynamic Behavior

We describe the ion pair-driven heterodimeric capsule formation of a cyclotricatechylene 1 and a boronic acid-appended hexahomotrioxacalix[3]arene 2. Although 1 does not interact with 2 in a protic solution, in the presence of Et4NAcO quantitative formation of a heterodimeric capsule via boronate esterification was observed in the NMR, a direct result of anion-induced boronate ester formation and the Et4N+ template. Reversible boronate esterification allowed us to selectively control capsule assembly using pH switching.

Orientational Isomerism Controlled by the Difference in Electronic Environments of a Self-Assembling Heterodimeric Capsule

Tetrakis(4-hydroxyphenyl)-cavitand 1 and tetra(4-pyridyl)-cavitand 2 self-assemble into a heterodimeric capsule 1.2 via four ArOH...pyridyl hydrogen bonds in CDCl3. The 1.2 expresses the orientational isomerism of an encapsulated unsymmetrical guest with high orientational selectivity because the electronic environment of the 1 unit is different from that of the 2 unit. For p-ethoxyiodobenzene and 2-iodo-6-methoxynaphthalene encapsulated in 1.2, the iodo group is specifically oriented to the cavity of the 2 unit. The orientational isomeric selectivity for methyl p-acetoxybenzoate and methyl p-ethoxybenzoate within 1.2 is 1:0.11 and 1:<0.05, respectively, wherein the methyl ester group is preferentially oriented to the cavity of the 2 unit. The delicate balance among electrostatic potential repulsion, CH-pi interaction, or CH-halogen (halogen-pi) interaction, in 1.2-guest assembly influences the orientational isomeric selectivity of unsymmetrical guests within 1.2.

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.

Reasons for the exclusive formation of heterodimeric capsules between tetra-tolyl and tetra-tosylurea calix[4]arenes

The selective heterodimerization of tetra-tolyl () and tetra-tosylurea () calixarenes, serendipitously found by Rebek et al. (R. K. Castellano, B. H. Kim and J. Rebek, Jr., J. Am. Chem. Soc., 1997, 119, 12671-12672), has been used for the construction of highly sophisticated macrocycles and well-defined supramolecular assemblies. Regrettably, hitherto, neither the exact structure of these heterodimers nor the reason for their exclusive formation is known. We present molecular dynamics simulations using the AMBER force field in explicit chloroform solvent for the two homodimers, the heterodimer and the two uncomplexed tetra-urea calixarenes. The rigid rotation about the C-S-N-C bond of the tosylurea group has been calculated for a model compound (N-mesylformamide) at the RHF/6-31G* level of theory. The calculations suggest that the heterodimer . is energetically favored over the homodimers by a sterically relaxed conformation of the tosylurea hemisphere in ., by a moderate degree of reorganization of the hemispheres from the uncomplexed to the complexed state and by favorable interactions between the hemispheres. The tosylurea S=O groups are involved in the hydrogen bonding system which results in different sizes of the three capsules in increasing order . < . < .. To prove the computational predictions, 1H NMR experiments have been carried out with solvents/guests differing in shape and size. The largest capsule . prefers the larger guests toluene and p-xylene while the latter is not encapsulated in the smallest capsule ..

C-Pentyltetra(3-pyridyl)cavitand: A Versatile Building Block for the Directed Assembly of Hydrogen-Bonded Heterodimeric Capsules

Hydrogen-bond-directed assembly of heterodimeric cavitand-based capsules is of considerable interest. Herein, we report the synthesis and single-crystal X-ray structure determination of a pyridyl-functionalized cavitand that contains suitable hydrogen-bond acceptor moieties for the construction of asymmetric cavitand-based capsules. [structure: see text]

A pyridyl-functionalized cavitand: Starting point for hydrogen-bond driven assembly of heterodimeric capsules

The directed assembly of derivatized cavitands into nano-sized supramolecular hosts is of considerable interest. This manuscript describes the synthesis and structural characterization of a pyridyl-functionalized cavitand that, in principle, can act as one half of a large number of hydrogen-bonded heterodimeric capsules when matched with a variety of suitably functionalized cavitands.

Orientational Isomerism and Binding Ability of Nonsymmetrical Guests Encapsulated in a Self‐Assembling Heterodimeric Capsule

The ability of a guest to induce the assembly of tetracarboxyl-cavitand 1 and tetra(3-pyridyl)-cavitand 2 into a heterodimeric capsule 12, and the orientational isomerism of nonsymmetrical p-disubstituted-benzene guests encapsulated in 12, are described. For example, the ability of a guest to induce the assembly of guest subset(12) increases in the order p-iodoaniline< or =p-chloroanisole < p-bromoanisole < N-methyl-p-iodoaniline < p-iodoanisole. For these five guests encapsulated in 12, the halogen atoms are specifically oriented with respect to the cavity of the 2 unit. By contrast, the orientational isomeric selectivities of p-chloroiodobenzene, p-bromoiodobenzene, and p-methylanisole encapsulated in 12 are quite low, in the range of 1:1.7 to 1:1. The ortho-fluoro derivatives of these three guests, however, are encapsulated in 12 with a highly selective orientation, in which the substituent next to the fluorine atom greatly prefers the cavity of the 2 unit to that of the 1 unit.

Guest-induced assembly of tetracarboxyl-cavitand and tetra(3-pyridyl)-cavitand into a heterodimeric capsule via hydrogen bonds and CH-halogen and/or CH-pi interaction: control of the orientation of the encapsulated guest.

The guest- or solvent-induced assembly of a tetracarboxyl-cavitand 1 and a tetra(3-pyridyl)-cavitand 2 into a heterodimeric capsule 1.2 in a rim-to-rim fashion via four intermolecular CO(2)H.N hydrogen bonds has been investigated both in solution and in the solid state. In the (1)H NMR study, a 1:1 mixture of1a and 2a (R = (CH(2))(6)CH(3)) in CDCl(3) gave a mixture of various complicated aggregates, whereas this mixture in CDCl(2)CDCl(2) or p-xylene-d(10) exclusively produced the heterodimeric capsule 1a.2a. It was found that an appropriate 1,4-disubstituted-benzene is a suitable guest for inducing the exclusive formation of 1a.2a in CDCl(3). The ability of a guest to induce the formation of guest-encapsulating heterodimeric capsule, guest@(1a.2a), increased in the order p-ethyltoluene < 1-ethyl-4-methoxybenzene < or = 1-ethyl-4-iodobenzene < or = 1,4-dibromobenzene < 1-iodo-4-methoxybenzene < or= 1,4-dimethoxybenzene < or = 1,4-diiodobenzene. The (1)H NMR study revealed that a CH-halogen interaction between the inner protons of the methylene-bridge rims (-O-H(out)CH(in)-O-) of the 1a and 2a units and the halogen atoms of 1,4-dihalobenzenes and a CH-pi interaction between the methoxy protons of 1,4-dimethoxybenzene and the aromatic cavities of the 1a and 2a units play important roles in the formation of 1,4-dihalobenzene@(1a.2a) and 1,4-dimethoxybenzene@(1a.2a), respectively. A preliminary single-crystal X-ray diffraction analysis of guest@(1b.2b) (R = (CH(2))(2)Ph; guest = 1-iodo-4-methoxybenzene or p-xylene) confirmed that the guest encapsulated in 1b.2b is oriented with the long axis of the guest along the long axis of 1b.2b and that the iodo and the methoxy groups of the encapsulated 1-iodo-4-methoxybenzene are specifically oriented with respect to the cavities of the 2b and 1b units, respectively.

"Flexiball" toolkit: a modular approach to self-assembling capsules.

We report the synthesis and characterization of new, self-assembling molecular capsules. The modular strategy makes use of glycoluril building blocks available in multigram amounts combined with aromatic spacer elements. The lengthy syntheses encountered with earlier generations of capsules are avoided, and several capsules of nanometer dimensions are now accessible. Single bond attachments between spacers and glycoluril modules result in monomers as dimeric capsules that are less rigid than their earlier counterparts. The host-guest properties of the homo- and heterodimeric capsules were studied using a combination of NMR and ESI-mass spectrometry. They show a less pronounced selectivity for guests of different sizes, and their increased flexibility prevents self-assembly when no rigidifying elements are present on the central spacer unit. Some of the new capsules bear inwardly directed, secondary amide N-H protons. These can be further functionalized, as shown by their methylation to give tertiary analogues. The structures hold broader implications for the placement of functional groups on concave molecular surfaces.