Cyclic Host Research Articles

Self‐Inclusion Complexation of Electron‐Accepting Guest into Electron‐Donating Cyclic Host by Photoexcitation

AbstractSelf‐inclusion complexes consisting of host‐guest conjugates are one of the unique supramolecular structures because they form in‐state and out‐state depending on the external stimuli. Despite many reports of the stimuli‐responsive self‐inclusion complex formation, study of the structural relaxation from out‐state to in‐state by photoexcitation has been unexplored. Herein, we report that an electron‐donating host and an electron‐accepting guest conjugate exhibits the structural relaxation from out‐state to in‐state by photoexcitation. Formation of the in‐state in the excited state resulted in exciplex emission along with the locally excited emission from the out‐state. Moreover, this structural relaxation by photoexcitation was suppressed not only by temperature, but also by the presence of guest molecules, resulting in changes in the ratio of the dual emission intensities.

Self-Inclusion Complexation of Electron-Accepting Guest into Electron-Donating Cyclic Host by Photoexcitation.

Self-inclusion complexes consisting of host-guest conjugates are one of the unique supramolecular structures because they form in-state and out-state depending on the external stimuli. Despite many reports of the stimuli-responsive self-inclusion complex formation, study of the structural relaxation from out-state to in-state by photoexcitation has been unexplored. Herein, we report that an electron-donating host and an electron-accepting guest conjugate exhibits the structural relaxation from out-state to in-state by photoexcitation. Formation of the in-state in the excited state resulted in exciplex emission along with the locally excited emission from the out-state. Moreover, this structural relaxation by photoexcitation was suppressed not only by temperature, but also by the presence of guest molecules, resulting in changes in the ratio of the dual emission intensities.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

The Dynamic Chemistry of Orthoesters and Trialkoxysilanes: Making Supramolecular Hosts Adaptive, Fluxional, and Degradable.

ConspectusThe encapsulation of ions into macro(bi)cyclic hosts lies at the core of supramolecular chemistry. While chemically inert hosts such as crown ethers (synthesis) and cyclodextrins (Febreze) have enabled real-world applications, there is a wider and accelerating trend toward functional molecules and materials that are stimuli-responsive, degradable, or recyclable. To endow supramolecular hosts with these properties, a deviation from ether C-O bonds is required, and functional groups that engage in equilibrium reactions under relatively mild conditions are needed.In this Account, we describe our group's work on supramolecular hosts that comprise orthoester and trialkoxysilane bridgeheads. In their simplest structural realization, these compounds resemble both Cram's crown ethers (macrocycles with oxygen donor atoms) and Lehn's cryptands (macrobicycles with 3-fold symmetry). It is therefore not surprising that these new hosts were found to have a natural propensity to bind cations relatively strongly. In recent work, we were also able to create anion-binding hosts by placing disubstituted urea motifs at the center of the tripodal architecture. Structural modifications of either the terminal substituents (e.g., H vs CH3 on the bridgehead), the diol (e.g., chiral), or the bridgehead atom itself (Si vs C) were found to have profound implications on the guest-binding properties.What makes orthoester/trialkoxysilane hosts truly unique is their dynamic covalent chemistry. The ability to conduct exchange reactions with alcohols at the bridgehead carbon or silicon atom is first and foremost an opportunity to develop highly efficient syntheses. Indeed, all hosts presented in this Account were prepared via templated self-assembly in yields of up to 90%. This efficiency is remarkable because the macrobicyclic architecture is established in one single step from at least five components. A second opportunity presented by dynamic bridgeheads is that suitable mixtures of orthoester hosts or their subcomponents can be adaptive, i.e. they respond to the presence of guests such that the addition of a certain guest can dictate the formation of a preferred host. In an extreme example of dynamic adaptivity, we found that ammonium ions can fulfill the dual role of catalyst for orthoester exchange and cationic template for efficient host formation, representing an unprecedented example of a fluxional supramolecular complex. The third implication of dynamic bridgeheads is due to the reaction of orthoesters and trialkoxysilanes with water instead of alcohols. We describe in detail how the hydrolysis rate differs strongly between O,O,O-orthoesters, S,S,S-trithioorthoesters, and trialkoxysilanes and how it is tunable by the choice of substituents and pH.We expect that the fundamental insights into exchange and degradation kinetics described in this Account will be useful far beyond supramolecular chemistry.

Responsive pillar[n]arene materials

AbstractIntelligent materials with responsive behaviors toward external stimuli, such as light, temperature, pH, redox, and solvent have been increasingly fascinating. Reversible noncovalent interactions provide an efficient way to construct stimuli‐responsive materials. Macrocyclic compounds, such as cyclodextrins, cucurbit[n]urils, calix[n]arenes, crown ethers, and related macrocycles, are useful skeletons for constructing such materials through host–guest interactions. Pillar[n]arenes are pillar‐shaped macrocyclic hosts developed by our groups in 2008, in which the repeated 1,4‐dialkoxybenzene units are connected by methylene bridges at the para position. The versatile functionality, easy modification, excellent size‐dependent host–guest complexation, and adjustable electron density of the cavity endow pillar[n]arenes with excellent properties compared with other cyclic host molecules. Moreover, the unique planar chirality and chirality inversion generated by unit rotation make pillar[n]arenes ideal platforms for investigating chirality inversion, induction, and transformation. In this review, we describe stimuli‐responsive topological, optical, chiroptical, supramolecular assemblies, and solid‐state materials based on the host–guest complexation and structural regulation of pillar[n]arenes.

Capture and Removal of Iodine by a Fluorinated Leaning Pillar[6]arene with Host–Guest Interactions

AbstractVolatile radioactive pollutants are posing great challenges to global environment. Volatile radioactive iodine, which is one of the primary environmental pollutants from nuclear power plants, spreads rapidly in water and air and increases risk to human health. Therefore, the research for appropriate adsorbents to capture iodine with long‐term storage is crucial. In this study, we report that easily obtained fluorinated leaning pillar[6]areneFP6is a new adsorbent for iodine capture with robust moisture and thermal stability. Crystalline solidFP6solid can capture not only volatile iodine in the air but also iodine dissolved in aqueous solutions with fast adsorption speed and high up‐take capacity. Host–guest interactions betweenFP6and iodine indicates that iodine molecule is threaded into the cavity of the cyclic hostFP6to form a host‐guest complex driven by C−F ⋅⋅⋅ I halogen bonding interactions. Moreover, the regeneration ofFP6is simple and efficient, and it can be regenerated at least five times by simply heating under vacuum at 120 °C for 3 hours without losing iodine capture capacity. The excellent iodine pollutant removal ability demonstrates the promise ofFP6for pollutant treatment.

Efficient Cyclization of Linear Polymer with Pseudopolyrotaxane Assistance

The physical properties of cyclic polymers differ from those of linear polymers. To prepare cyclic polymers, the ends of a linear polymer must intramolecularly react. Cyclic polymers are typically synthesized at low concentration because intermolecular linkage is preferential to intramolecular linkage at high concentrations. Therefore, preparation of cyclic polymers at high concentrations is difficult. This study demonstrates a new approach to obtain cyclic polymers from highly concentrated polymer solutions using pseudo-polyrotaxanes (pPRxs). Cyclic polymers are prepared by penetrating a linear polymer into the cavity of a cyclic host to form pPRx and then the ends of the linear polymer are subsequently connected. Our approach allows the synthesis of cyclic polymers at concentration that do not allow conventional cyclic polymer synthesis. Specifically, although without pPRx, almost no cyclic polymers were obtained (<1%), with pPRx, the cyclic polymer was obtained as the main product (proportion of cyclic PEG 14%).

Cothreading of Unmodified and Monoazidated β-Cyclodextrins in Polyrotaxanes for Orthogonal Modification of Cell-Penetrating Peptides via Click Chemistry

To establish a method for the orthogonal chemical functionalization of β-cyclodextrin (β-CD)-based polyrotaxane (PRX), unmodified and monoazidated β-CDs (N3-β-CDs) were utilized as cyclic host molecules for synthesizing PRXs. PRXs were successfully synthesized by using N3-β-CD, and the molar ratio of unmodified β-CD and N3-β-CD in the resulting PRXs could be regulated by the feed ratio of unmodified β-CD and N3-β-CD. It was revealed that all PRX molecules contained N3-β-CD, indicating that unmodified and monoazidated β-CDs were cothreaded onto a single polymer axis. Physicochemical characterization of β-CD/N3-β-CD cothreaded PRXs suggested that their crystalline structures were unaffected by the molar ratio of N3-β-CD, whereas their thermal stability was slightly improved with increasing molar ratio of N3-β-CD. To facilitate cellular internalization of PRXs, threaded N3-β-CD in PRXs was modified with cell-penetrating octaarginine (R8) peptides via a copper(I)-catalyzed azide–alkyne click reaction. The cellular internalization efficiency of the R8-modified PRXs increased with the number of R8 peptides modified on PRXs. However, PRXs modified with a large number of R8 peptides precipitated in serum solutions and exhibited high cytotoxicity. PRXs modified with the optimal number of R8 peptides did not exhibit precipitation and showed high cellular uptake compared to unmodified PRXs without cytotoxicity. Consequently, PRXs modified with the optimal number of R8 peptides showed superior cholesterol-reducing effects in fibroblasts derived from patients with Niemann–Pick type C disease. As demonstrated here, the number of modified functional molecules plays a crucial role in the treatment effects of PRXs, and β-CD/N3-β-CD cothreaded PRXs can offer potential for orthogonal postmodification. Thus, β-CD/N3-β-CD cothreaded PRXs could introduce benefits that enable the material applications of PRXs.

Fatigue Resistance of Photochromic Diarylethene in the Presence of Cyclodextrins with Different Pore Sizes

Abstract Among the various types of photochromic compounds, diarylethenes have good fatigue resistance, but further improvement is required. In this study, we investigated photochromic reaction behavior and fatigue resistance by inclusion in cyclodextrin (CD), which is a cyclic host molecule with three different pore sizes. A water-soluble diarylethene (DE1) synthesized in this work exhibited reversible photochromism in water. Continuous irradiation with UV light resulted in the formation of its byproduct. The addition of αCD showed no improvement of fatigue resistance. However, the addition of βCD and γCD suppressed a side reaction to result in the improvement of fatigue resistance. Especially, the addition of γCD gave a large improvement. To clarify the relationship between fatigue resistance of DE1 and the pore size of CD, the host-guest interaction between DE1 and CD was investigated using NOESY spectra. The results indicate that the depth of DE1 included in CD shows a large effect on suppression of the side reaction of DE1.

Improved Recovery and Selectivity of Lanthanide-Ion-Binding Cyclic Peptide Hosts by Changing the Position of Acidic Amino Acids

The development of an effective host molecule to separate lanthanide (Ln) ions and a method for predicting its guest recognition/self-assembly behavior based on primary chemical structures are highly sought after in both academia and industry. Herein, we report the improvement of one-pot Ln ion recovery and a performance prediction method for four new cyclic peptide hosts that differ in the position of acidic amino acids. These cyclic peptide hosts could recognize Ln3+ directly through a 1:1 complexation–precipitation process and exhibited high Lu3+ selectivity in spite of similar ion size and electronegativity when the positions of the acidic amino acids were changed. This unpredictable selectivity was explained by considering the dipole moment, lowest unoccupied molecular orbital, and cohesion energy. In addition, a semi-empirical function using these parameters was proposed for screening the sequence and estimating the isolated yields without long-time molecular dynamics calculations. The insights obtained from this study can be employed for the development of high-performance peptides for the selective recovery of Ln and other metal ions, as well as for the construction of diverse supramolecular recognition systems.

Noncovalently bound and mechanically interlocked systems using pillar[n]arenes.

Pillar[n]arenes are pillar-shaped macrocyclic compounds owing to the methylene bridges linking the para-positions of the units. Owing to their unique pillar-shaped structures, these compounds exhibit various excellent properties compared with other cyclic host molecules, such as versatile functionality using various organic synthesis techniques, substituent-dependent solubility, cavity-size-dependent host-guest properties in organic media, and unit rotation along with planar chiral inversion. These advantages have enabled the high-yield synthesis and rational design of pillar[n]arene-based mechanically interlocked molecules (MIMs). In particular, new types of pillar[n]arene-based MIMs that can dynamically convert between interlocked and unlocked states through unit rotation have been produced. The highly symmetrical pillar-shaped structures of pillar[n]arenes result in simple NMR spectra, which are useful for studying the motion of pillar[n]arene wheels in MIMs and creating sophisticated MIMs with higher-order structures. The creation and application of polymeric MIMs based on pillar[n]arenes is also discussed.

Phenol Derivatives as Co-Crystallized Templates to Modulate Trimesic-Acid-Based Hydrogen-Bonded Organic Molecular Frameworks

Five host−guest trimesic-acid-based hydrogen-bonds framework compounds with different guests, namely [(TMA)4·(TMB)3] (1), [(TMA)2·(DMB)1.5] (2), [(TMA)6·(MP)] (3), [(TMA)·(EP)] (4) and [(TMA)·(PP)] (5) (TMA = trimesic acid, TMB = 1,3,5-trimethoxybenzene, DMB = 1,4-dimethoxybenzene, MP = 4-methoxyphenol, EP = 4-ethoxyphenol and PP = 4-propoxyphenol), were obtained through co-crystallization, and were characterized by elemental analysis, infrared spectroscopy analysis, and thermogravimetric analysis. The trimesic acid molecules comprise a hydrogen bonding six-membered cyclic host network that is found in a two-dimensional arrangement in compounds 1 and 2, and in a nine-fold interpenetrated three-dimensional structure in compound 3. In compounds 4 and 5, the trimesic acid and EP/PP molecules form a hydrogen-bonded six-membered cyclic network, resulting in a one-dimensional chain structure through O−H…O hydrogen bonds.

Transmembrane Fluoride Transport by a Cyclic Azapeptide With Two β-Turns.

Diverse classes of anion transporters have been developed, most of which focus on the transmembrane chloride transport due to its significance in living systems. Fluoride transport has, to some extent, been overlooked despite the importance of fluoride channels in bacterial survival. Here, we report the design and synthesis of a cyclic azapeptide (a peptide-based N-amidothiourea, 1), as a transporter for fluoride transportation through a confined cavity that encapsulates fluoride, together with acyclic control compounds, the analogs 2 and 3. Cyclic receptor 1 exhibits more stable β-turn structures than the control compounds 2 and 3 and affords a confined cavity containing multiple inner –NH protons that serve as hydrogen bond donors to bind anions. It is noteworthy that the cyclic receptor 1 shows the capacity to selectively transport fluoride across a lipid bilayer on the basis of the osmotic and fluoride ion-selective electrode (ISE) assays, during which an electrogenic anion transport mechanism is found operative, whereas no transmembrane transport activity was found with 2 and 3, despite the fact that 2 and 3 are also able to bind fluoride via the thiourea moieties. These results demonstrate that the encapsulation of an anionic guest within a cyclic host compound is key to enhancing the anion transport activity and selectivity.

Crown ether-pillararene hybrid macrocyclic systems.

A combination of Nobel macrocycle-crown ether and star macrocycle-pillararenes together in organic synthesis and material science is significant in obtaining hybrid systems, with rigid/flexible structural architecture, induced planar chirality, a negative cooperative effect and multiple fused cyclic hosts. In this review, we will discuss the synthesis/preparation of crown ether-pillararene hybrid macrocyclic systems by covalent bonds, supramolecular interactions and mechanical bonds, leading to hybrid compounds, supramolecular assemblies and mechanically interlocked molecules. The practical applications of crown ether-containing pillararenes will also be discussed in diverse areas, such as molecular recognition via fused multiple macrocycles and ion channels as well as external stimuli-responsive smart materials. We also call the attention of related researchers towards academic and technical issues about topological structures and applied functions in this fresh new fused macrocyclic field.

The Green Box: An Electronically Versatile Perylene Diimide Macrocyclic Host for Fullerenes.

The powerful electron accepting ability of fullerenes makes them ubiquitous components in biomimetic donor-acceptor systems that model the intermolecular electron transfer processes of Nature's photosynthetic center. Exploiting perylene diimides (PDIs) as components in cyclic host systems for the noncovalent recognition of fullerenes is unprecedented, in part because archetypal PDIs are also electron deficient, making dyad assembly formation electronically unfavorable. To address this, we report the strategic design and synthesis of a novel large, macrocyclic receptor composed of two covalently strapped electron-rich bis-pyrrolidine PDI panels, nicknamed the "Green Box" due to its color. Through the principle of electronic complementarity, the Green Box exhibits strong recognition of pristine fullerenes (C60/70), with the noncovalent ground and excited state interactions that occur upon fullerene guest encapsulation characterized by a range of techniques including electronic absorption, fluorescence emission, NMR and time-resolved EPR spectroscopies, cyclic voltammetry, mass spectrometry, and DFT calculations. While relatively low polarity solvents result in partial charge transfer in the host donor-guest acceptor complex, increasing the polarity of the solvent medium facilitates rare, thermally allowed full electron transfer from the Green Box to fullerene in the ground state. The ensuing charge separated radical ion paired complex is spectroscopically characterized, with thermodynamic reversibility and kinetic stability also demonstrated. Importantly, the Green Box represents a seminal type of C60/70 host where electron-rich PDI motifs are utilized as recognition motifs for fullerenes, facilitating novel intermolecular, solvent tunable ground state electronic communication with these guests. The ability to switch between extremes of the charge transfer energy continuum is without precedent in synthetic fullerene-based dyads.

Functionalization of Cyclodextrin Derivatives to Create Supramolecular Pharmaceutical Materials

Molecular recognition is useful in creating functional supramolecular materials. Non-covalent bond formations, such as host-guest interactions, hydrogen bonding, and electrostatic interaction, are effective tools for introducing various functions and properties into materials. This review focuses on such macroscopic functions as selective molecular adhesion, self-healing, toughness, and the actuation of supramolecular polymeric materials-materials which have potential in pharmaceutical development. These functions have been achieved using reversible bonding between cyclodextrins (CDs; cyclic host molecules) and guest molecules. For example, macroscopic adhesions between host-modified hydrogels and guest-modified hydrogels have been investigated. CD-modified hydrogels were found to show selective adhesion to a guest hydrogel with an appropriate molecular size for the CD cavity, indicating that the host-guest complex formation between the gels led to the adhesive behavior. Surprisingly, polymeric materials having host-guest cross-linking points show both high toughness and flexibility, unlike conventional covalently cross-linked materials. These materials also exhibited self-healing properties, capable of repairing damage to the materials. Furthermore, the supramolecular materials demonstrated macroscopic rapid expansion and contraction driven by external stimuli under wet or semi-dry conditions, in which the supramolecular gels vary the cross-linking density between the polymers accordingly. Different topological gels are able to vary the length of the polymer chain between cross-linking points to show large deformation. Both types of actuators were found to exhibit externally stimulated flexing behaviors. This review summarizes recent advancements in the development of these supramolecular materials, which appear to be promising new components in pharmaceutical science.

Unbiased Rotational Motions of an Ellipsoidal Guest in a Tight Yet Pliable Host

AbstractIn the design of machinery such as steel bearings, a fundamental understanding of material characteristics provides an indispensable basis for the design. Although hydrocarbon cycloarylenes have started to be used for providing unique supramolecular bearings with anomalous dynamic behaviors, their fundamental understanding is immature. A unique property of the cycloarylene host is now reported: the cyclic host is so pliable that it tracks the orientational changes of the ellipsoidal guest, that is, C70 fullerene. Unique structures of the complex were revealed by spectroscopic and crystallographic analyses, and additional theoretical investigations deepened our understanding by revealing the structural changes associated with unbiased rotational motions.

Host-Guest Binding Hierarchy within Redox- and Luminescence-Responsive Supramolecular Self-Assembly Based on Chalcogenide Clusters and γ-Cyclodextrin.

Water-soluble salts of anionic [Re6 Q8 (CN)6 ]4- (Q=S, Se, Te) chalcogenide octahedral rhenium clusters react with γ-cyclodextrin (γ-CD) producing a new type of inclusion compounds. Crystal structures determined through single-crystal X-ray diffraction analysis revealed supramolecular host-guest assemblies resulting from close encapsulations of the octahedral cluster within two γ-CDs. Interestingly, nature of the inner Q ligands influences strongly the host-guest conformation. The cluster [Re6 S8 (CN)6 ]4- interacts preferentially with the primary faces of the γ-CD while the bulkier clusters [Re6 Se8 (CN)6 ]4- and [Re6 Te8 (CN)6 ]4- exhibit specific interactions with the secondary faces of the cyclic host. Furthermore, analysis of the crystal packing reveals additional supramolecular interactions that lead to 2D infinite arrangements with [Re6 S8 (CN)6 ]4- or to 1D "bamboo-like" columns with [Re6 Se8 (CN)6 ]4- and [Re6 Te8 (CN)6 ]4- species. Solution studies, using multinuclear NMR methods, ESI-MS and Isothermal titration calorimetry (ITC) corroborates nicely the solid-state investigations showing that supramolecular pre-organization is retained in aqueous solution even in diluted conditions. Furthermore, ITC analysis showed that host-guest stability increases significantly ongoing from S to Te. At last, we report herein that deep inclusion alters significantly the intrinsic physical-chemical properties of the octahedral clusters, allowing redox tuning and near IR luminescence enhancement.

Dynamic materials fabricated from water soluble pillar[n]arenes bearing triethylene oxide groups

Pillar[n]arenes are a new kind of supramolecular macrocyclic hosts which have developed rapidly due to their unique topology and high functionality, giving rise to many applications in the construction of interesting and functional materials. Among them, water-soluble pillar[n]arenes bearing triethylene oxide (TEO) chains have drawn increasing research interest due to their advantageous properties. In this review, we summarized the recent progress of dynamic materials fabricated from water soluble pillar[n]arenes bearing TEO groups, including thermoresponsive materials with lower critical solution temperature (LCST) behavior, cyclic host liquids, and smart windows. It is anticipated that more and more ‘smart’ supramolecular materials based on modified pillar[n]arenes will be developed in this burgeoning area of research.

Evidences for Inclusion and Encapsulation of an Ionic liquid with β-CD and 18-C-6 in Aqueous Environments by Physicochemical Investigation.

The interface between pyrrolidinium-based ionic liquid, i.e., 1-ethyl-1-methylpyrrolidinium bromide, with β-cyclodextrin and 18-crown-6 solution have been compared and explored by means of density, viscosity, refractive index, electrical conductance and surface tension, FTIR, 1H nuclear magnetic resonance, 2D ROESY NMR, and high resolution mass spectroscopy studies. Limiting apparent molar volumes (ϕV0), experimental slopes (SV*) interpreted in terms of inclusion and interaction (ion-solvent, ion-ion). Establishment of binding affinity were discussed in molecular terms supported this inclusion complexation and encapsulation interaction process. The result shows that the stability of the resulting complexes of β-cyclodextrin:[EMPyrr]+ and 18-crown-6:[EMPyrr]+ is based on the geometrical and spectrometric data. Host guest chemistry of the five-membered nitrogen containing cation with two different macro cyclic hosts is supported by studying NMR. HRMS has been used to support the complexation process with the proper stoichiometry ratio. The solid complex formations were established by Fourier transform infrared study.