Recent Applications of Pillararene-Inspired Water-Soluble Hosts.

Pillararenes and their derivatives have emerged in supramolecular chemistry as unique macrocycles for applications in host-guest chemistry, materials science and biomimetics. Many variations have been conceived and synthesized in recent years and in this review, we relate progress in water-soluble versions: leaning towerarenes, extended-pillararenes, biphenarenes, helicarenes and octopusarenes. These are applied in targeted drug delivery, selective uptake and release of aromatic guests, fabrication of gold/silver and mesoporous silica nanoparticles, cell imaging, pollutant separation, biomedicine (e.

Recent progress using novel tetraphenylethylene-based macrocyclic hosts in water.

Macrocyclic structures are popular in supramolecular chemistry and have enjoyed considerable success as platforms for elaboration to container compounds and new materials. Host/guest studies in organic media have relied heavily on structures derived from crown ethers, calixarenes, cucurbiturils, resorcinarenes and pillararenes over the past decades. More recently, their water-soluble versions have been developed for potential applications in biology.

Modeling Amine Methylation in Methyl Ester Cavitand.

Methylation of amines inside an introverted resorcinarene-based deep methyl ester cavitand is investigated by means of molecular dynamics simulations and quantum chemical calculations. Experimentally, the cavitand has been shown to bind a number of amines and accelerate the methylation reaction by more than four orders of magnitude for some of them. Eight different amines are considered in the present study, and the geometries and energies of their binding to the cavitand are first characterized and analyzed.

Control of reactivity and selectivity in isomerization and rearrangement reactions inside confined spaces.

In the confined space of supramolecular systems, the substrate can be forced into a reactive conformation and labile intermediates may be stabilized while isolated from the bulk solution. In this highlight, unusual processes mediated by supramolecular hosts are described. These include unfavourable conformational equilibria, unusual product selectivities in bond and ring-chain isomerizations, accelerated rearrangement reactions through labile intermediates, and encapsulated oxidations.

Selective Binding and Isomerization of Oximes in a Self-Assembled Capsule.

A series of straight-chain (C7-C13) alkyl--methyl aldoximes (R-C(H)═NOMe) were synthesized with various functional groups at the remote ends (alkenes, halogen, -COOH, and NH). Their isomers about the C═N bond showed ∼60-40% -ratio in organic solutions. Surprisingly, their confinement in a water-soluble capsule with benzoselenodiazole walls shows high selectivity for the -/-isomer.

Recent Advances in the Applications of Water-soluble Resorcinarene-based Deep Cavitands.

We review here the use of container molecules known as cavitands for performing organic reactions in water. Central to these endeavors are binding forces found in water, and among the strongest of these is the hydrophobic effect. We describe how the hydrophobic effect can be used to drive organic molecule guests into the confined space of cavitand hosts.

Role of Rim Functions in Recognition and Selectivity of Small-Molecule Guests in Water-Soluble Cavitand Hosts.

Groups on the upper rim of cavitands can play major roles in the recognition of small molecules. Water-soluble deep cavitands 1, 2 or 3 bearing the walls upper rim of imidazole, urea, and methyl urea, respectively, were synthesized and characterized as hosts of small-molecule guests. The vase forms of 1 or 2 are stabilized through H-bonding to solvent water molecules between adjacent walls.

Binding and Assembly of a Benzotriazole Cavitand in Water.

A water-soluble cavitand bearing a benzotriazole upper rim was prepared and characterized. It exists as a dimeric velcraplex in D O, but forms host-guest complexes with hydrophobic and amphiphilic guests. Alkanes (C5 to C10), cyclic ketones (C6-C10), cyclic alcohols (C6-C8) and various amphiphilic guests form 1 : 1 cavitand complexes.

Organic radical reactions confined to containers in supramolecular systems.

Radical chemistry and host-guest chemistry have each developed rapidly over the past decades and their intersection offers an attractive opportunity for modern applications. Radicals can be introduced into the frameworks of supramolecular hosts or radicals can be guests, generated in and confined to host containers. In this highlight we outline research achievements in both approaches, photoinduced and external reagent-initiated radicals in the host.

Rigidified Cavitand Hosts in Water: Bent Guests, Shape Selectivity, and Encapsulation.

We report the synthesis and characterization of two water-soluble container compounds (cavitand hosts) with rigidified open ends. One cavitand uses four (CH)'s as spacers to bridge the adjacent walls, while another cavitand uses four CHCHOCHCH's bridges and features a wider open end. The spacers preorganize the deep cavitands into vase-like, receptive shapes and prevent their unfolding to the unreceptive kite-like conformation.

The role of electric field, peripheral chains, and magnetic effects on significant H upfield shifts of the encapsulated molecules in chalcogen-bonded capsules.

The chalcogen-bonded homo-cavitand and hetero-cavitand AY+AY' capsules (Y, Y' = Se, Te), as well as their encapsulated complexes with one or two guest molecules have been studied theoretically density functional theory (DFT), while the H NMR spectra of the homo-cavitand encapsulated complexes (in ASe+ASe) have been measured experimentally. There is excellent agreement between theoretical and experimental spectra. In all cases, we found significant H upfield shifts which are more intense in the ASe+ASe cage compared to the ATe+ATe and ASe+ATe cages.

Water and the Cation-π Interaction.

The cation-π interaction and the hydrophobic effect are important intermolecular forces in chemistry and play major roles in controlling recognition in biological systems. We compared their relative contributions to the binding of molecular "dumbbell" guests in synthetic container hosts in water. The guests offered direct, intramolecular competition between trimethylammonium groups, -N(CH), and -butyl groups, -C(CH), for the internal surfaces (aromatic panels) of the containers.

Recognition of hydrophilic molecules in deep cavitand hosts with water-mediated hydrogen bonds.

We describe new container host molecules - deep cavitands with benzimidazole walls and ionic feet - to recognize highly hydrophilic guest molecules in water. The aromatic surfaces of the cavity recognize hydrophobic portions of the guest while bound water molecules mediate hydrogen bonding in the complex. Spectroscopic (NMR) evidence indicates slow in/out exchange on the chemical shift timescale and thermodynamic (ITC) methods show large association constants (Ka up to 6 × 10 M) for complexation of small, water-soluble molecules such as THF and dioxane.

Hydrophobic and Metal-Coordinated Confinement Effects Trigger Recognition and Selectivity.

We report the synthesis and characterization of a new water-soluble cavitand . The container features 2-aminobenzimidazole panels at the "rim" and pyridiniums at the "feet". In the solid state, a single-crystal X-ray structure of the organic-soluble precursor showed a stable vase form.

Recognition of Hydrophilic Cyclic Compounds by a Water-Soluble Cavitand.

A water-soluble deep cavitand bearing amides on the upper rim and trimethyl ammonium groups on the feet was synthesized. The open-ended cavity is stabilized by the intramolecular hydrogen bonds formed between the adjacent amides, and the introduction of trimethylammonium imparts to the cavitand good solubility in water. The cavitand exhibits high binding affinity and selectivity to hydrophilic molecules in water.

Dimeric capsules self-assembled through halogen and chalcogen bonding.

Supramolecular capsules are nanoscale containers useful for the study of molecular behavior in confined spaces. They offer practical applications in catalysis, molecular transport, drug delivery, and materials science. Self-assembly has proven to be an effective approach in constructing supramolecular capsules and a variety of well-known noncovalent interactions including hydrogen bonding, metal coordination and ionic interactions have been deployed.

Selective Macrocycle Formation in Cavitands.

The traditional end-to-end cyclization of long-chain linear precursors is difficult and often unpredictable because the unfavorable entropy of macrocyclic closure allows undesired intermolecular reactions to compete. Here, we apply cavitands to the selective intramolecular aldol/dehydration reaction of long-chain α,ω-dialdehydes in aqueous solution. Hydrophobic forces drive the dialdehydes into the cavitands in folded conformations and favor macrocyclization reactions over intermolecular reactions observed in bulk solution.

Highly Selective Radical Monoreduction of Dihalides Confined to a Dynamic Supramolecular Host.

Reduction of alkyl dihalide guests (2-5 and 7) with trialkylsilanes (R SiH) was performed in water-soluble host 1 to investigate the effects of confinement on fast radical reactions (k≥10  m  s ). High selectivity (>95 %) for mono-reduced products was observed for primary and secondary dihalide guests under mild conditions. The results highlight the importance of host-guest complexation rates to modulate the product selectivity in radical reactions.

Aromaticity and Chemical Bonding of Chalcogen-Bonded Capsules Featuring Enhanced Magnetic Anisotropy.

We present a theoretical study of chalcogen bonded container capsules (A +A ) where X=O, S, Se, and Te, and their encapsulation complexes with n-C H (n-C H @A +A ). Both Se and Te encapsulation complexes have significant experimental and computed binding energies, analogous to the hydrogen bonded counterparts, while the S and O capsules and their encapsulation complexes show only weak binding energies, which are attributed to different types of bonding: chalcogen S⋅⋅⋅N bonds for S-capsules and π-π stacking and weak hydrogen bonds for the O case. All A +A and C H @A +A present unusually high magnetic anisotropies in their interiors.

Confined molecules: experiment meets theory in small spaces.

The behavior of molecules confined to small spaces is fascinating chemistry and lies at the heart of signaling processes in biology. Our approach to confinement is through reversible encapsulation of small molecules in synthetic containers. We show that confinement leads to amplified reactivities in bimolecular reactions, stabilization of otherwise reactive species, and limitation in motions that create new stereochemical arrangements.

Binding selectivity and separation of p-functionalized toluenes with a metallo-cavitand in water.

A metallo-cavitand (1-2Pd) showed unprecedented binding selectivity and sequestration of p-functionalized toluene isomers in water. The host-guest complexation was studied using 1H and COSY NMR methods and xylene-isomer complexes were examined by using DFT calculations. A liquid-liquid extraction scheme was developed for the separation of p-functionalized toluenes.

Modeling the Reaction of Carboxylic Acids and Isonitriles in a Self-Assembled Capsule.

Quantum chemical calculations were used to study the reaction of carboxylic acids with isonitriles inside a resorcinarene-based self-assembled capsule. Experimentally, it has been shown that the reactions between p-tolylacetic acid and n-butyl isonitrile or isopropyl isonitrile behave differently in the presence of the capsule compared both with each other and also with their solution counterparts. Herein, the reasons for these divergent behaviors are addressed by comparing the detailed energy profiles for the reactions of the two isonitriles inside and outside the capsule.

Kinetic Stabilities and Exchange Dynamics of Water-Soluble Bis-Formamide Caviplexes Studied Using Diffusion-Ordered NMR Spectroscopy (DOSY).

A deep cavitand binds long-chain trans,trans- and trans,cis-bis-formamide isomers in water solution giving a pair of caviplexes in a ca. 60:40 ratio. Both caviplexes display in/out guest exchange dynamics that are slow on the H NMR chemical shift timescale, but fast on the EXSY timescale.

Chalcogen Bonding and Hydrophobic Effects Force Molecules into Small Spaces.

Supramolecular capsules are desirable containers for the study of molecular behavior in small spaces and offer applications in transport, catalysis, and material science. We report here the use of chalcogen bonding to form container assemblies that are stable in water. Cavitands - functionalized with 2,1,3-benzoselenadiazole walls were synthesized in good yield from resorcin[4]arenes.

Radical Reactions in Cavitands Unveil the Effects of Affinity on Dynamic Supramolecular Systems.

Radical reduction of alkyl halides and aerobic oxidation of alkyl aromatics are reported using water-soluble container compounds ( and ). The reductions involve α,ω-dihalides (- and ) with radical initiators in cavitand hosts with varied binding affinities. Product distributions lead to general guidelines for the use of dynamic supramolecular systems with fast reactions.