Theoretical Study on the Conformational Conversion of 1,3-Dioxane Inside a Capsular Host

The mechanism for the conformational conversion of 1,3-dioxane guest encapsulated inside a capsular host was theoretically investigated using semiempirical PM3 method and DFT methods. The free-state process of the conformational conversion of 1,3-dioxane was also investigated to make a comparison between the two different states using the same theory. The influences of the inner phase of the capsule on the conformational conversion of guest molecule were discussed via analyzing the comparative results. It was found that the capsular host could accommodate 1,3-dioxane within its cavity by the weak attractive interactions between host and guest, and it responds to the conformational conversion of guest by the deformation of hydrogen-bonding seam at the middle of the capsule. When entrapped in the capsule, the guest molecule undergoes the conformational conversion from chair form to twist-boat form slower than that under the free condition. The deformation of the capsule is favorable to maximize the attractive interactions between host and guest.     

Restricted motion of guests confined in carceplexes and capsules

Guest orientation within carceplexes and capsules was determined qualitatively from NMR data, and the molecular mobility of guests was determined via coalescence of (1)H NMR signals. Both are highly dependent on guest size and shape, as is interconversion of twistomers. Incarceration of 1,4-thioxane results in a large (1.8 kcal/mol) constraint on thioxane's conformational mobility (chair-to-chair interconversion). Similar conformational constraints (1.6 kcal/mol) were determined for 1,4-dioxane both when incarcerated in carceplex 1b and when encapsulated reversibly in capsule 3b. Encapsulation-induced conformational constraints of this magnitude are unprecedented, and are particularly striking for the noncovalently linked capsules.     

Structural alteration of hybrid supramolecular capsule induced by guest encapsulation

Heterofunctionalized C(2v) symmetrical cavitand 1 with 4-pyridylethynyl and 3-carbamoylphenyl groups in alternating arrangement was designed and synthesized. A 1:1 mixture of the cavitand 1 and a cis-coordinated palladium(II) or platinum(II) complex self-assembled into a hybrid supramolecular capsule via both metal-ligand coordination bonds and hydrogen bonds. Formation of the capsular assembly was confirmed by NMR spectroscopy and mass spectrometry. The hybrid capsule encapsulated the appropriate guest, the molecular sizes of which fit the size of the capsular cavity. Structural alteration of the hybrid capsule was induced by the guest encapsulation. A C(2h) structure for the encapsulation complex was assigned by 2D NMR spectra analysis. Thermodynamic and kinetic properties of the guest encapsulation were investigated. The kinetics of in/out guest exchange was strongly influenced by hydrogen bonding in the hybrid capsule.     

Supramolecular self-assembly of water-soluble cavitands: investigated by molecular dynamics simulation

In this study, we have examined supramolecular self-assembly process of a hydrophobic guest with a water-soluble host known by the trivial name octa acid (OA). Two octa acids form a capsular assembly only in presence of a nonpolar guest(s). Size and shape of the guest control the stoichiometry of the capsular complex. Here, all atom molecular dynamics simulation has been utilized to investigate complex formation mechanisms of a nonpolar guest (nonylbenzene) with two OA cavitands. Nonylbenzene was encapsulated into the nonpolar cavity of OA capsule owing to solvophobic interactions. Upon encapsulation it was twisted and bent due to lack of free space within the capsule. These unusual forms obtained from the simulation study were in accord with experimental findings. The post-complexation attributes of the guest were regulated by the available free space within the OA and favorable non-covalent interactions between the guest and the walls of the OA capsule. In the identical simulation condition two OA cavitands did not form a capsule without a guest, thus indicating requirement of a guest during the self-assembly of OA cavitands.     

Transformation of a C-methylcalix[4]resorcinarene-based host-guest complex from a wave-like to a novel triangular brick-wall architecture

A novel 2D triangular brick-wall framework based on CMCR and bpe with included ruthenocene guest molecules is formed with time by conversion of a 1D wave-like polymer structure with an accompanying bowl-to-boat conformational change of the CMCR molecules.     

A PM3 Molecular Orbital Study on the Conformational Equilibrium of Cyclohexane upon α-Cyclodextrin Inclusion Complexation

The effect ofα-cyclodextrin (α-CD) inclusion complexation on the conformational equilibrium of cyclo- hexane wasstudied with thesemiempirical PM3 molecularorbital calculations. The calculation results indicated that the chair form of cyclohexane is 18.5 kJ·mol-1lower than that of boat one in energy, however, theα-cyclodextrin inclusion complex of boat cycl ohexane is 4.4 kJ·mol-1more stable than the complex of chair form. It demon-strated that the conformational equilibrium of cyclohexane was influenced by theα-CD inclusion complexation. Hence, caution should be given when extrapolating the conformational behaviors of the guest compounds in the supramolecular systems totheir free forms, since the interactionsbetween the host and guest significantly affect the conformation of the guest compounds.     

ITC and NMR analysis of the encapsulation of fatty acids within a water-soluble cavitand and its dimeric capsule

We report here NMR and Isothermal Titration Calorimetry studies of the binding of ionisable guests (carboxylate acids) to a deep-cavity cavitand. These studies reveal that the shortest guests favoured 1:1 complex formation, but the longer the alkyl chain the more the 2:1 host-guest capsule is favoured. For intermediate-sized guests, the equilibrium between these two states is controlled by pH; at low values the capsule containing the carboxylic acid guest is favoured, whereas as the pH is raised deprotonation of the guest favours the 1:1 complex. Interestingly, for one host–guest pair the energy required to decap the 2:1 capsular complex and form the 1:1 complex is sufficient to shift the pK_a of the guest by ~3–4 orders of magnitude (4.1–5.4 kcal mol^?1). The two largest guests examined form stable 2:1 capsules, with in both cases the guest adopting a relatively high energy J-shaped motif. Furthermore, these 2:1 complexes are sufficiently stable that at high pH guest deprotonation occurs without decapping of the capsule.     

Templation of the excited-state chemistry of alpha-(n-alkyl) dibenzyl ketones: how guest packing within a nanoscale supramolecular capsule influences photochemistry

Excited-state behavior of eight alpha-alkyl dibenzyl ketones (alkyl = CH3 through n-C8H17) that are capable of undergoing type II and/or type I photoreactions has been explored in isotropic solution and within a water-soluble capsule. The study consisted of two parts: photochemistry that explored the excited-state chemistry and an NMR analysis that revealed the packing of each guest within the capsule. The NMR data (COSY, NOESY, and TOCSY experiments) revealed that ternary complexes between alpha-alkyl dibenzyl ketones and the capsule formed by two cavitands are kinetically stable, and the guests fall into three packing motifs modulated by the length of the alpha-alkyl chain. In essence, the host is acting as an external template to promote the formation of distinct guest conformers. The major products from all eight guests upon irradiation either in hexane or in buffer solution resulted from the well-known Norrish type I reaction. However, within the capsule the excited-state chemistry of the eight ketones was dependent on the alkyl chain length. The first group consisted of alpha-hexyl, alpha-heptyl, and alpha-octyl dibenzyl ketones that yielded large amounts of Norrish type II products within the host, while in solution the major products were from Norrish type I reaction. The second group consists of alpha-butyl and alpha-pentyl dibenzyl ketones that yield equimolar amounts of two rearranged starting ketones within the capsule (combined yield of ca 60%), while in solution no such products were formed. The third group consisted of alpha-methyl, alpha-ethyl, and alpha-propyl dibenzyl ketones that within the capsule yielded only one (not two) rearranged starting ketone in larger amounts (21-35%) while in solution no rearrangement product was obtained. Variation in the photochemistry of the guest within the capsule, with respect to the alpha-alkyl chain length of the guest, highlights the importance of how a small variation in supramolecular structure can influence the selectivity within a confined nanoscale reactor.     

Highly selective recognition of diols by a self-regulating fine-tunable methylazacalix[4]pyridine cavity: guest-dependent formation of molecular-sandwich and molecular-capsule complexes in solution and the solid state

The molecular recognition of methylazacalix[4]pyridine (MACP-4; 1) towards various diols was investigated by using (1)H NMR spectroscopic and X-ray diffraction analysis. As a unique macrocyclic host molecule that undergoes conformational inversions very rapidly in solution, MACP-4 has been shown to self-regulate its conformation, through the formation of different conjugations of the four bridging nitrogen atoms with their adjacent pyridine rings, to form a cavity that best fits the guest species through intermolecular hydrogen-bond, C-H...pi, and pi-pi interactions between the host and guest. As a consequence, depending upon the diol structure and geometry, MACP-4 forms a 1:1 molecular sandwich, 2:1 molecular capsule, and 1:2 butterfly-layered complex with the guests. As a result of favorable enthalpy and entropy effects, MACP-4 exhibits excellent selectivity in the recognition of resorcinol, thus resulting in a very stable 1:1 sandwich complex with resorcinol with a binding constant of 6000 (M-1). The dynamic (1)H NMR spectroscopic study demonstrated that the 1,3-alternate conformation of the macrocyclic ring of the MACP-4resorcinol complex (13) is stable at low temperature (T<243 K), and its conformational inversion requires a larger activation energy (DeltaG++=(45.5+/-2.2) kJ mol(-1)). In the presence of an excess amount of resorcinol, however, the conformational inversion of the MACP-4resorcinol complex proceeds more readily with a decreased activation energy (DeltaG++=(33.5+/-1.5) kJ mol(-1)) owing most probably to the favorable enthalpy effect of the [3...1...3]++transition state.     

Hydrogen-bonded encapsulation complexes in protic solvents

We describe here the behavior of the hydrogen-bonded capsule 1.1 and its complexes in protic solvents. The kinetics and thermodynamics of the encapsulation process were determined through conventional (1)H NMR methods. The enthalpies and entropies of encapsulation are both positive, indicating a process that liberates solvent molecules. The rates of dissociation-association of the capsule were comparable to the rates for the in-out exchange of large guests, which suggests that guest exchange occurs by complete dissociation of the capsule in protic solvents. The stability of the hydrogen-bonded capsule 1.1 toward protic solvents depends strongly on the guests, with the best guest being dimethylstilbene 8. The results establish guidelines for the properties of capsules that could be accessed in water.     

Templated xerogels as platforms for biomolecule-less biomolecule sensors

We designed and synthesized new armed 12-oxacrown-3s bearing oxygen donor arms and forming encapsulated complexes with metal ions. The ISEs based on the single armed 12-oxacrown-3s exhibited Na⁺ ion selectivity, while the ISE based on the double armed 12-oxacrown-3 exhibited Li⁺ ion selectivity. The conformational analysis was performed on the free armed 12-oxaciown-3s and the non-encapsulated and the encapsulated armed 12-oxacrown-3 complexes using a semi-empirical method. The conformational analysis indicated that all armed 12-oxacrown-3s structurally prefer the Na⁺ ion rather than the Li⁺ ion. Further, it became apparent that the single armed 12-oxacrown-3s without a guest cation have the C_3v 12-oxaciown-3 ring and the double armed 12-oxacrown-3 without a guest cation has the bent 12-oxacrown-3 ring. The oxygens except carbonyl oxygens were directed toward the cation center in the structures of the complexes. It was clear that the ether and ester oxygens participate in the sidearm coordination.     

Restricted guest tumbling in phosphorylated self-assembled capsules

ABii diphosphonatocavitands self-assemble in chloroform solution to form dimeric molecular capsules. The molecular capsules can incarcerate an N-methylpyridinium or N-methylpicolinium guest. We have demonstrated that the supramolecular assembly acts as a molecular rotor as a result of the restricted motion of the guest inside the molecular cavity. In the solid state, X-ray diffraction analysis of the free host showed that two cavitands interact through strong hydrogen bonds to give the supramolecular self-assembled capsule. The solid-state structure of the N-methylpicolinium complex is comparable to that of the free host and indicates that the guest is not a prerequisite for the formation of the capsule. DOSY NMR studies provided a definitive argument for the formation of the free and complexed supramolecular capsule in CDCl(3) solution. In solution, the tumbling of the N-methylpyridinium and N-methylpicolinium guests about the equatorial axes of the host can be frozen and differs by the respective energy barriers, with the larger picolinium substrate having a larger value (ΔG(++) = 69.7 kJ mol(-1)) than the shorter pyridinium guest (ΔG(++) = 44.8 kJ mol(-1)). This behavior corresponds to the restricted rotation of a rotator in a supramolecular rotor.     

Chiral Encapsulation by Directional Interactions

The complexation of chiral guests in the cavity of dimeric self‐assembled chiral capsule 1 ₂ was studied by using NMR spectroscopy and X‐ray crystallography. Capsule 1 ₂ has walls composed of amino acid backbones forming numerous directional binding sites that are arranged in a chiral manner. The polar character of the interior dictates the encapsulation preferences towards hydrophilic guests and the ability of the capsule to extract guests from water into an organic phase. Chiral discrimination towards hydroxy acids was evaluated by using association constants and competition experiments, and moderate de values were observed (up to 59 %). Complexes with one or two guest molecules in the cavity were formed. For 1:1 complexes, solvent molecules are coencapsulated; this influences guest dynamics and makes the chiral recognition solvent dependent. Reversal of the preferences can be induced by coencapsulation of a nonchiral solvent in the chiral internal environment. For complexes with two guests, filling of the capsule’s internal space can be very effective and packing coefficients of up to 70 % can be reached. The X‐ray crystal structure of complex 1 ₂?((S) ‐6 )₂ with well‐resolved guest molecules reveals a recognition motif that is based on an extensive system of hydrogen bonds. The optimal arrangement of interactions with the alternating positively and negatively charged groups of the capsule’s walls is fulfilled by the guest carboxylic groups acting simultaneously as hydrogen‐bond donors and acceptors. An additional guest molecule interacting externally with the capsule reveals a possible entrance mechanism involving a polar gate. In solution, the structural features and dynamic behavior of the D₄‐symmetric homochiral capsule were analyzed by variable‐temperature NMR spectroscopy and the results were compared with those for the S₈‐symmetric heterochiral capsule.     

An NMR study of the rates of single-molecule exchange in a cylindrical host capsule

Self-assembled cylindrical capsule 1 is reversibly formed from dimerization of two tetraimide resorcinarenes. Studies of guest exchange involving host capsule 1 reveal a mechanistic continuum for exchange that depends on the structure of the guest. Kinetic and dynamic NMR measurements demonstrate the direct displacement of one guest by another. Surprisingly, in the case of benzene exchange in the pairwise encapsulation of benzene and p-xylene, the incoming benzene occupies the same half of the capsule as the outgoing benzene. As the size of the guests increases, solvent-bridged intermediates determine the rates; empty volumes on the molecular scale need not be invoked.     

Host–guest complexes between cryptophane‐C and chloromethanes revisited

Cryptophane‐C is composed of two nonequivalent cyclotribenzylene caps, one of which contains methoxy group substituents on the phenyl rings. The two caps are connected by three OCH₂CH₂O linkers in an anti arrangement. Host–guest complexes of cryptophane‐C with dichloromethane and chloroform in solution were investigated in detail by nuclear magnetic resonance techniques and density functional theory (DFT) calculations. Variable temperature proton and carbon‐13 spectra show a variety of dynamic processes, such as guest exchange and host conformational transitions. The guest exchange was studied quantitatively by exchange spectroscopy measurements or by line‐shape analysis. The conformational preferences of the guest‐containing host were interpreted through cross‐relaxation measurements, providing evidence of the gauche+2 and gauche?2 conformations of the linkers. In addition, the mobility of the chloroform guest inside the cavity was studied by carbon‐13 relaxation experiments. Combining different types of evidence led to a detailed picture of molecular recognition, interpreted in terms of conformational selection. Copyright © 2012 John Wiley & Sons, Ltd.     

Metallohosts with a heart of carbon

Single-crystal X-ray diffraction studies have confirmed that Ni(3)S(3)-based molecular bowls prepared in one-pot reactions capture either CH(2)Cl(2) or C(60). The nature of the pendant substituents (naphthalen-2-ylmethyl, benzyl, or ethyl) around the rim of the bowl dictates the formation of a 1:1 (bowl host-C(60) guest) or 2:1 (capsule host-C(60) guest) architecture. In CDCl(3), the trimeric complexes were found to be in equilibrium with dimeric analogues. For the naphthalen-2-ylmethyl-substituted host, NMR spectroscopic titration data confirmed a 1:1 host-C(60) guest complex in 1,2-Cl(2)C(6)D(4) solution.     

Guest encapsulation and self-assembly of a cavitand-based coordination capsule

The synthesis and spectroscopic characterization of a cavitand-based coordination capsule 14 BF4 of nanometer dimensions is described. Encapsulation studies of large aromatic guests as well as aliphatic guests were performed by using 1H NMR spectroscopy in [D1]chloroform. In addition to the computational analysis of the shape and geometry of the capsule, an experimental approach to estimate the interior size of the cavity is discussed. The cavity provides a highly rigid binding space in which molecules with lengths of approximately 14 A can be selectively accommodated. The rigid cavity distinguished slight structural differences in the flexible alkyl-chain guests as well as the rigid aromatic guests. The detailed thermodynamic studies revealed that not only CH-pi interactions between the methyl groups on the guest termini and the aromatic cavity walls, but also desolvation of the inner cavity play a key role in the guest encapsulation. The cavity preferentially selected the hydrogen-bonded heterodimers of a mixture of two or three carboxylic acids 18-20. The chiral capsule encapsulated a chiral guest to show diastereoselection.     

EPR Studies of the Binding Properties,Guest Dynamics,and Inner‐Space Dimensions of a Water‐Soluble Resorcinarene Capsule

Nitroxide free radicals have been used to study the inner space of one of Rebek’s water‐soluble capsules. EPR and ¹H NMR spectroscopy, ESI‐MS, and DFT calculations showed a preference for the formation of 1:2 complexes. EPR titrations allowed us to determine binding constants (K_a) in the order of 10⁷ M ^?2. EPR spectral‐shape analysis provided information on the guest rotational dynamics within the capsule. The interplay between optimum hydrogen bonding upon capsule formation and steric strain for guest accommodation highlights some degree of flexibility for guest inclusion, particularly at the center of the capsule where the hydrogen bond seam can be barely distorted or slightly disturbed.     

Structural characterization of modular supramolecular architectures in solution

Structures of modular supramolecular architectures consisting of a hexameric, diphenylethyne-linked porphyrin macrocyclic array and the corresponding host-guest complex formed by inclusion of a tripyridyl guest molecule were characterized in solution using high-angle X-ray scattering. Scattering measurements made to 6 A resolution coupled with pair distance function (PDF) analyses demonstrated that (1) the porphyrin architectures are not rigid but are distributed across a conformational ensemble with a mean diameter that is 1.5 A shorter than the diameter of a symmetric, energy-minimized model structure, (2) the conformational envelope has limits of 3 A positional dispersion and full rotational freedom for all six porphyrin groups, and (3) insertion of the tripyridyl guest molecule expands the diameter of the host conformer by 0.6 A and decreases the configurational dispersion by approximately 2-fold. These results validate the molecular design, provide a new measure of conformational ensembles in solution that cannot be obtained by other techniques, and establish a structural basis for understanding the photophysical and guest-hosting functions of the hexameric porphyrin architectures in liquids.     

Tunable capsule space: self-assembly of hemispherical cavitands with hydrogen-bonding linkers

Fine and/or drastic tuning of capsule space has been attained by alteration of the hydrogen-bonding linker and/or hemispherical cavitand, respectively. Two molecules of tetracarboxyl-cavitand 1 or tetrakis(4-carboxyphenyl)-cavitand 2 as a hemisphere and four molecules of 2-aminopyrimidine (2-AP) or tetrahydro-2-pyrimidinone (THP) as an equatorial hydrogen-bonding linker self-assemble into a capsule [(1)2.(2-AP)4] (3), [(1)2.(THP)4] (4), [(2)2.(2-AP)4] (5), or [(2)2.(THP)4] (6), respectively, via 16 hydrogen bonds. These capsules provide isolated nanospace and can encapsulate one guest molecule (7-13) in solution. Each capsule has a different cavity size and shows particular guest selectivity on the competitive encapsulation experiments.