Maximizing Coordination Capsule–Guest Polar Interactions in Apolar Solvents Reveals Significant Binding

Guest encapsulation underpins the functional properties of self‐assembled capsules yet identifying systems capable of strongly binding small organic molecules in solution remains a challenge. Most coordination capsules rely on the hydrophobic effect to ensure effective solution‐phase association. In contrast, we show that using non‐interacting anions in apolar solvents can maximize favorable interactions between a cationic Pd₂L₄ host and charge‐neutral guests resulting in a dramatic increase in binding strength. With quinone‐type guests, association constants in excess of 10⁸ m ^?1 were observed, comparable to the highest previously recorded constant for a metallosupramolecular capsule. Modulation of optoelectronic properties of the guests was also observed, with encapsulation either changing or switching‐on luminescence not present in the bulk phase.     

Fluorescent Cross‐Linked Supramolecular Polymer Constructed by Orthogonal Self‐Assembly of Metal–Ligand Coordination and Host–Guest Interaction

A new host molecule consists of four terpyridine groups as the binding sites with zinc(II) ion and a copillar[5]arene incorporated in the center as a spacer to interact with guest molecule was designed and synthesized. Due to the 120 ° angle of the rigid aromatic segment, a cross‐linked dimeric hexagonal supramolecular polymer was therefore generated as the result of the orthogonal self‐assembly of metal–ligand coordination and host–guest interaction. UV/Vis spectroscopy, ¹H NMR spectroscopy, viscosity and dynamic light‐scattering techniques were employed to characterize and understand the cross‐linking process with the introduction of zinc(II) ion and guest molecule. More importantly, well‐defined morphology of the self‐assembled supramolecular structure can be tuned by altering the adding sequence of the two components, that is, the zinc(II) ion and the guest molecule. In addition, introduction of a competitive ligand suggested the dynamic nature of the supramolecular structure.     

Selective Host–Guest Interactions of a Transformable Coordination Capsule/Tube with Fullerenes

An M₂L₄ coordination capsule or an M₂L₂ coordination tube was selectively formed by the combination of Hg^II hinges and bent bispyridine ligands. The two structures reversibly interconvert at room temperature in response to modulation of the metal‐to‐ligand ratio and exhibit different host–guest interaction behavior. The capsule alone encapsulates large spherical molecules, fullerenes C₆₀ and C₇₀, and the bound guests are released upon capsule‐to‐tube transformation by the simple addition of metal ions.     

Host–Guest Binding‐Site‐Tunable Self‐Assembly of Stimuli‐Responsive Supramolecular Polymers

Despite the remarkable progress made in controllable self‐assembly of stimuli‐responsive supramolecular polymers (SSPs), a basic issue that has not been consideration to date is the essential binding site. The noncovalent binding sites, which connect the building blocks and endow supramolecular polymers with their ability to respond to stimuli, are expected to strongly affect the self‐assembly of SSPs. Herein, the design and synthesis of a dual‐stimuli thermo‐ and photoresponsive Y‐shaped supramolecular polymer (SSP2) with two adjacent β‐cyclodextrin/azobenzene (β‐CD/Azo) binding sites, and another SSP (SSP1) with similar building blocks, but only one β‐CD/Azo binding site as a control, are described. Upon gradually increasing the polymer solution temperature or irradiating with UV light, SSP2 self‐assemblies with a higher binding‐site distribution density; exhibits a flower‐like morphology, smaller size, and more stable dynamic aggregation process; and greater controllability for drug‐release behavior than those observed with SSP1 self‐assemblies. The host–guest binding‐site‐tunable self‐assembly was attributed to the positive cooperativity generated among adjacent binding sites on the surfaces of SSP2 self‐assemblies. This work is beneficial for precisely controlling the structural parameters and controlled release function of SSP self‐assemblies.     

Doubly Cavitand‐Capped Porphyrin Capsule by Hydrogen Bonds

The components of a 1:2 mixture of meso‐tetrakis(4‐dodecyl‐3,5‐dihydroxyphenyl)porphyrin ( 1 ) and a bowl‐shaped tetrakis(4‐pyridylethynyl)cavitand ( 2 ) in CDCl₃ or C₆D₆ self‐assemble quantitatively into the doubly cavitand‐capped porphyrin capsule 2?1?2 through eight ArOH ??? Npy hydrogen bonds. Capsule 2?1?2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1‐acetoxy‐3,5‐dimethoxybenzene ( G ) as a guest to form G / G @( 2?1?2 ). Remarkable solvent effect was observed, in which the apparent association constant of 2?1?2 with G in C₆D₆ was much greater than that in CDCl₃.     

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.     

Emerging Supramolecular Therapeutic Carriers Based on Host–Guest Interactions

Recent advances in host–guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non‐covalent interactions provide vast possibilities of manipulating supramolecular self‐assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self‐assemblies through host–guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli‐responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co‐delivery and site‐specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host–guest chemistry with biological interface science are proposed.     

Constructing Adaptive Photosensitizers via Supramolecular Modification Based on Pillararene Host–Guest Interactions

In order to promote the development of photodynamic therapy (PDT), undesired side effects like low tumor specificity and the “always‐on” phenomenon should be avoided. An effective solution is to construct an adaptive photosensitizer that can be activated to generate reactive oxygen species (ROS) in the tumor microenvironment. Herein, we design and synthesize a supramolecular switch based on a host–guest complex containing a water‐soluble pillar[5]arene ( WP5 ) and an AIEgen photosensitizer ( G ). The formation of the host–guest complex WP5 ? G quenches the fluorescence and inhibits ROS generation of G . Benefitting from the pH‐responsiveness of WP5 , the binding site between G and WP5 changes in an acidic environment through a shuttle movement. Consequently, fluorescence and ROS generation of the host–guest complex can be switched on at pH 5.0. This work offers a new paradigm for the construction of adaptive photosensitizers by using a supramolecular method.     

Metal–Organic Spheres as Functional Systems for Guest Encapsulation

Music of the spheres : Infinite coordination polymerization of Zn²⁺ ions and a multitopic ligand produces metal–organic micro‐ and nanospheres that can be used as functional matrices. The spheres can encapsulate combinations of active substances, such as organic dyes, magnetic nanoparticles, or luminescent quantum dots (see image), which results in spheres that are luminescent in the blue, green, and red regions of the spectrum.

     

Exploiting Host–Guest Interactions for the Synthesis of a Rod–Rod Block Copolymer with Crystalline and Liquid‐Crystalline Blocks

By making use of the host–guest interactions between the host molecule tris‐o‐phenylenedioxycyclotriphosphazene (TPP) and the rod–coil block copolymer (BCP) poly(ethylene oxide)‐block‐poly(octyl 4′‐octyloxy‐2‐vinylbiphenyl‐4‐carboxylate) (PEO‐b‐PVBP), the supramolecular rod–rod block copolymer P(EO@TPP)‐b‐PVBP was constructed. It consists of a crystalline segment P(EO@TPP) with a hexagonal crystalline structure and a columnar nematic liquid‐crystalline segment (PVBP). As the PVBP segments arrange themselves as columnar nematic phases, the crystalline structure of the inclusion complex P(EO@TPP), which has a smaller diameter, is destroyed. The self‐assembled nanostructure is thus clearly affected by the interplay between the two blocks. On the basis of wide‐ and small‐angle X‐ray scattering analysis, we conclude that the supramolecular rod–rod BCP can self‐assemble into a cylinder‐in‐cylinder double hexagonal structure.     

Size‐ and Orientation‐Selective Encapsulation of C70 by Cycloparaphenylenes

The size‐ and orientation‐selective formation of the shortest‐possible C₇₀ peapod in solution and in the solid state by using the shortest structural unit of an “armchair” carbon nanotube (CNT), cycloparaphenylene (CPP), has been studied. [10]CPP and [11]CPP exothermically formed 1:1 complexes with C₇₀, thereby giving the resulting peapods. A van′t Hoff plot analysis revealed that the formation of these complexes in 1,2‐dichlorobenzene was mainly driven by entropy, whereas the theoretical calculations suggested that the formation of the complex in the gas phase was predominantly driven by enthalpy. C₇₀ was found to exist in two distinct orientations inside the CPP cavity, namely “lying” and “standing”, depending on the specific size of the CPP. The theoretical calculations and the X‐ray crystallographic analysis revealed that the interactions between [10]CPP and the short axis of C₇₀ in its lying orientation were isotropic and similar to those observed between [10]CPP and C₆₀. However, the interactions between [11]CPP and C₇₀ in its standing orientation were anisotropic, thereby involving the radial deformation of [11]CPP into an ellipsoidal shape. This “induced fit” maximized the van der Waals interactions with the long axis of C₇₀. Theoretical calculations revealed that the deformation occurred readily with low energy loss, thus suggesting that CPPs are highly radially elastic molecules. These results also indicate that the same type of radial deformation should occur in CNT peapods that encapsulate anisotropic fullerenes.     

Modulation of Protein Dimerization by a Supramolecular Host–Guest System

Two sets of cyan and yellow fluorescent proteins, monomeric analogues, and analogues with a weak affinity for dimerization were functionalized with supramolecular host–guest molecules by expressed protein ligation. The host–guest elements induce selective assembly of the monomeric variants into a supramolecular heterodimer. For the second set of analogues, the supramolecular host–guest system acts in cooperation with the intrinsic affinity between the two proteins, resulting in the induction of a selective protein–protein heterodimerization at a more dilute concentration. Additionally, the supramolecular host–guest system allows locking of the two proteins in a covalent heterodimer through the facilitated and selective formation of a reversible disulfide linkage. For the monomeric analogues this results in a strong increase of the energy transfer between the proteins. The protein heterodimerization can be reversed in a stepwise fashion. The trajectory of the disassembly process differs for the monomeric and dimerizing set of proteins. The results highlight that supramolecular elements connected to proteins can both be used to facilitate the interaction between two proteins without intrinsic affinity and to stabilize weak protein–protein interactions at concentrations below those determined by the actual affinity of the proteins alone. The subsequent covalent linkage between the proteins generates a stable protein dimer as a single species. The action of the supramolecular elements in concert with the proteins thus allows the generation of protein architectures with specific properties and compositions.     

Host–Guest Chemistry Within Cellulose Nanocrystal Gel Receptors

Cellulose nanocrystals (CNCs) spontaneously assemble into gels when mixed with a polyionic organic or inorganic salt. Here, we have used this ion‐induced gelation strategy to create functional CNC gels with a rigid tetracationic macrocycle, cyclobis(paraquat‐p‐phenylene) ( CBPQT ⁴⁺). Addition of [ CBPQT ]Cl₄ to CNCs causes gelation and embeds an active host inside the material. The fabricated CNC gels can reversibly absorb guest molecules from solution then undergo molecular recognition processes that create colorful host–guest complexes. These materials have been implemented in gel chromatography (for guest exchange and separation), and as elements to encode 2‐ and 3‐dimensional patterns. We anticipate that this concept might be extended to design a set of responsive and selective gel‐like materials functioning as, for instance, water‐pollutant scavengers, substrates for chiral separations, or molecular flasks.