Guest Encapsulation Research Articles

Complementary charge-driven encapsulation of functional protein by engineered protein cages in cellulo.

Charge-driven inclusion complex formation in live cells was examined using a degradation-prone fluorescent protein and a series of protein cages. The results show that sufficiently strong host-guest ionic interaction and an intact shell-like structure are crucial for the protective guest encapsulation.

Exo-cage catalysis and initiation derived from photo-activating host–guest encapsulation

We report a new class of photoredox catalysis arising from the non-covalent association of separately inactive coordination cage and guest.

Supramolecular detoxification of nitrogen mustard via host-guest encapsulation by carboxylatopillar[5]arene.

Nitrogen mustard (NM), a kind of alkylating agent similar to sulfur mustard, remains a threat to public health. However, there is nearly no satisfactory antidote for nitrogen mustard. Herein, we developed a supramolecular antidote to nitrogen mustard through efficient complexation of NM by carboxylatopillar[5]arene potassium salts (CP[5]AK). The cavity of methoxy pillar[5]arene (P5A) is sufficient to encapsulate NM with an association constant of 1.27 × 102 M-1, which was investigated by 1H NMR titration, density functional theory studies and independent gradient model studies. NM degrades to the reactive aziridinium salt (2) in the aqueous phase which irreversibly alkylates DNA and proteins, causing severe tissue damage. Considering the size/charge matching with toxic intermediate 2, water-soluble CP[5]AK was selected to encapsulate the toxic aziridinium salt (2), resulting in a high association constant of 4.10 × 104 M-1. The results of protection experiments of guanosine 5'-monophosphate (GMP) by CP[5]AK indicated that the formation of a complex could effectively inhibit the alkylation of DNA. Besides, in vitro and in vivo experiments also indicated that the toxicity of the aziridinium salt (2) is inhibited with the formation of a stable host-guest complex, and CP[5]AK has a good therapeutic effect on the damage caused by NM. This study provides a new mechanism and strategy for the treatment of NM exposure-induced skin injuries.

Dynamics of organophosphate guest encapsulation in heteroleptic coordination cages.

Heteroleptic coordination cages allow the design of different host structures that can bind guest molecules within their cavities. In a previous work, the energetics of organophosphate encapsulation in palladium(II)-based heteroleptic coordination cages that differ in terms of their ability to form hydrogen bonds have been investigated [Platzek et al., Endohedrally Functionalized Heteroleptic Coordination Cages for Phosphate Ester Binding, Angew. Chem., Int. Ed. 2022, 61, e2022093]. The present work focuses on the dynamics of this system. Dynamic information is obtained through the application of a Markov state model (MSM) to unbiased multi-microsecond atomistic molecular dynamics simulations of guest binding and release. The MSM reveals that both the bound state and the binding/unbinding pathways are highly dynamic, with different types of interactions mediating the binding of the diphenylphosphate guest. Thus, the simulations highlight the dynamic nature of the nanoconfinement in the host-guest systems, with possible implications for the use of such coordination cages as catalysts.

Host-Guest Encapsulation to Promote the Formation of a Multicomponent Trigonal-Prismatic Metallacage.

An inclusion complex of a trigonal-prismatic metallacage with two coronene guests was constructed by multicomponent coordination-driven self-assembly from a 90° platinum(II) acceptor [cis-Pt(PEt3)2(OTf)2], disodium terephthalate, and 2,4,6-tri(4-pyridyl)-1,3,5-triazine in the presence of excess coronene. This platinum(II)-based trigonal prism was found to be a highly matched host to simultaneously encapsulate two coronene molecules. The encapsulation of coronene can effectively promote the formation of a pure single-prismatic metallacage and can stabilize the self-assembled structure via strong π-π-stacking interactions between coronene and the metallacage.

Superstructures of Zeolitic Imidazolate Frameworks to Single- and Multiatom Sites for Electrochemical Energy Conversion.

The exploration of electrocatalysts with high catalytic activity and long-term stability for electrochemical energy conversion is significant yet remains challenging. Zeolitic imidazolate framework (ZIF)-derived superstructures are a source of atomic-site-containing electrocatalysts. These atomic sites anchor the guest encapsulation and self-assembly of aspheric polyhedral particles produced using microreactor fabrication. This review provides an overview of ZIF-derived superstructures by highlighting some of the key structural types, such as open carbon cages, 1D superstructures, hollow structures, and the interconversion of superstructures. The fundamentals and representative structures are outlined to demonstrate the role of superstructures in the construction of materials with atomic sites, such as single- and dual-atom materials. Then, the roles of ZIF-derived single-atom sites for the electroreduction of CO2 and electrochemical synthesis of H2 O2 are discussed, and their electrochemical performance for energy conversion is outlined. Finally, the perspective on advancing single- and dual-atom electrode-based electrochemical processes with enhanced redox activity and a low-impedance charge-transfer pathway for cathodes is provided. The challenges associated with ZIF-derived superstructures for electrochemical energy conversion are discussed.

Crystalline Metal-Peptide Networks: Structures, Applications, and Future Outlook.

Metal-peptide networks (MPNs), which are assembled from short peptides and metal ions, are considered one of the most fascinating metal-organic coordinated architectures because of their unique and complicated structures. Although MPNs have considerable potential for development into versatile materials, they have not been developed for practical applications because of several underlying limitations, such as designability, stability, and modifiability. In this review, we summarise several important milestones in the development of crystalline MPNs and thoroughly analyse their structural features, such as peptide sequence designs, coordination geometries, cross-linking types, and network topologies. In addition, potential applications such as gas adsorption, guest encapsulation, and chiral recognition are introduced. We believe that this review is a useful survey that can provide insights into the development of new MPNs with more sophisticated structures and novel functions.

Guest Encapsulation Scope of a Triptycene-Based Pd2L4 Coordination Cage

The scope of a lantern-shaped, triptycene-based Pd2L4 coordination cage to encapsulate various carbon-rich guests was investigated. The cage was found to bind two molecules of corannulene and a variety of C60 derivatives in moderate to quantitative yields. Non-disruptive extraction of encapsulated fullerene derivative PC61BM from the cage was demonstrated by the simple addition of CS2 into an acetonitrile solution of the host–guest complex. This process can be accomplished in a layer-to-layer fashion, and thus, the recovered cage can be further utilized in a recycling process. As this self-assembled host is readily synthesized and able to transfer fullerenes and a range of its derivatives into polar organic solvents, it allows facilitating purification, chemical modification and solid-state processing of fullerenes for a range of materials applications.

Stabilizing Entropically Driven Self-Assembly of Self-Immolative Polyurethanes in Water: A Strategy for Tunable Encapsulation Stability and Controlled Cargo Release

Stimuli-responsive amphiphilic polymer assemblies are of great interest in the area of targeted drug delivery applications as they can sequester guest molecules in one set of conditions and release them under another. Hence, developing a strategy of molar mass controlled synthesis, in-depth understanding of the thermodynamics of the self-assembly process, stabilization, and triggered guest release in a controlled fashion would be highly anticipated in the field of drug delivery applications. As polymer molar mass has a significant impact on the self-assembly process or material property of polymers, we focused on a methodology of controlled molar mass polyurethane synthesis using recycled plastic waste and synthesized a series of self-immolative amphiphilic polyurethanes of varying molar masses and polydispersity indexes. All of the polymers were equipped with periodically grafted triethyleneglycol monomethyl ether as a pendant, a redox-responsive disulfide bond, a tertiary amine, and an aromatic moiety on the backbone. In aqueous milieu, these polymers are found to form entropically driven nanoassemblies (ΔS > 0), which were further stabilized by supramolecular cross-linking via the synergistic effect of π–π stacking (aromatic moiety), H-bonding (urethane functionality), and hydrophobic interactions, which eventually amplifies the guest encapsulation stability. A guest release profile in the presence of a redox environment shows ∼65% release in a controlled fashion. Furthermore, the tertiary amine on the polymer backbone leads to the formation of positively charged nanoassemblies at the tumor-relevant pH (pH ∼ 6.5–6.8), which could potentially enhance the cellular uptake of nanocarriers in tumor cells. Thus, a strategy for molar mass controlled polyurethane synthesis, understanding the effect of polymer molar mass on thermodynamics of self-assembly, establishing a stable micellar nanostructure endowed with environment-specific surface charge modulation, and controlled guest release, we believe, will significantly contribute to the development of robust chemotherapeutics.

Construction of Photo-Responsive Pd2 L4 -Type Nanocages based on Feringa's Second-Generation Motor and Its Guest Binding Ability for C60.

We present the construction of a M2 L4 -type metal-organic nanocage featuring four endohedral Feringa's motor motifs and its adaptive encapsulation towards a C60 guest molecule. The structure of the cage, though complicated on the 1 H NMR spectrum due to the adoption of mixed ligands, was unambiguously characterized with a combination of ESI-MS, 2D DOSY, 13 C NMR and particularly the SAXS technique. The molecular motor within the cage demonstrated similar photophysical properties to the uncoordinated one, indicating the motor's function was not compromised when it was anchored in such a confined nanospace. Furthermore, the nanocage showed good guest encapsulation ability towards C60 , and a guest induced-fit behavior of the cage was revealed based on the extensive SAXS analysis and molecular dynamics simulation. The adaptive motorized nanocage reported here represents one of the very few examples of integrating individual motors into a discrete nanoconfined system and offers prospects to achieve its non-equilibrium functions.

Encapsulationof the Haloalkane 4‐Chloromethylpyridine Hydrochloride by Cucurbit[8]uril

AbstractComplexation of 4‐chloromethylpyridine hydrochloride (G) with cucurbit[8]uril (Q[8]) has been investigated using NMR spectroscopy, UV‐visible spectroscopy, isothermal titration calorimetry (ITC), Quantum calculation, and X‐ray crystallography. The data indicated that the guest 4‐chloromethylpyridine hydrochloride is completely encapsulated by the cavity of the Q[8] host in both aqueous solution and the solid state, generating a highly stable inclusion complex, namely G2@Q[8]. Interestingly, ion–dipole interactions and hydrogen‐bonding interactions play a central role in the formation of the inclusion complex G2@Q[8], which provides a reliable basis for the encapsulation of small organic guests by the hydrophobic microenvironment of the cavity.

Purely Covalent Molecular Cages and Containers for Guest Encapsulation.

Cage compounds offer unique binding pockets similar to enzyme-binding sites, which can be customized in terms of size, shape, and functional groups to point toward the cavity and many other parameters. Different synthetic strategies have been developed to create a toolkit of methods that allow preparing tailor-made organic cages for a number of distinct applications, such as gas separation, molecular recognition, molecular encapsulation, hosts for catalysis, etc. These examples show the versatility and high selectivity that can be achieved using cages, which is impossible by employing other molecular systems. This review explores the progress made in the field of fully organic molecular cages and containers by focusing on the properties of the cavity and their application to encapsulate guests.

Assembly of three sulfonylcalix[4]arene-based multinuclear complexes: Tunable structures and guest encapsulation properties

Understanding and controlling the structure of polymetallic clusters plays a fundamental role in supramolecular chemistry. Herein we describe the preparation of three sulfonylcalix[4]arenebased multinuclear cluster complexes, namely, [Fe4(TBSC)2(DMF)4(µ3-H2O)2(H2O)2·2MeCN] (1), [Fe2Na4(TBSC)2(DMF)4(µ6-H2O)(H2O)2] (2), and [Fe4(TBSC)(Py)4(µ4-H2O)] (3) from trivalent iron ions and p-tert-butylsulfonylcalix[4]arene ligands by the metal-directed assembly. These complexes exhibit interesting tunable core structures, exo cavities, supramolecular packing characteristics in the solid state. As a result, the three multinuclear complexes exhibit selective molecular recognition toward the dye molecules.

Mapping the Assembly of Neutral Tetrahedral Cages Tethered by Oximido Linkers and Their Guest Encapsulation Studies.

A primary criterion for the design of polyhedral metal-organic cages is the requirement of geometrically matched pairs of metal ions and ligand moieties. However, understanding the pathway it takes to reach the final polyhedral structure can provide more insights into the self-assembly process and improved design strategies. In this regard, we report two neutral tetrahedral cages with the formulas {[Pd3(NiPr)3PO]4(L1)6} (1-TD) and {[Pd3(NiPr)3PO]4(L2)6} (2-TD) starting from the acetate-bridged cluster {[Pd3(NiPr)3PO]2(OAc)2(OH)}2·2(CH3)2SO (HEXA-Pd) and the respective oxamide precursors (L1H2: [C2(NH2)2O2]) and (L2H2: (C2(NHMe)2O2]). When subtle variations in the reaction conditions were made, two new tetrameric Pd12 assemblies, {[Pd3(NiPr)3PO]4(L1)2(OAc)4(OMe)4} (1-TM) and {[Pd3(NiPr)3PO]4(L2)2(OAc)4(OMe)4} (2-TM), were obtained from the same precursors. Detailed investigations using NMR, mass spectrometry, X-ray crystallography, and computational studies indicate that the macrocyclic complexes 1-TM and 2-TM are the reaction intermediates involved in the formation of the tetrahedral cages 1-TD and 2-TD, respectively. Moreover, the tetrahedral cages 1-TD and 2-TD exhibited intrinsic cavities of volume ∼85 Å3. Guest encapsulation studies revealed that the cage 1-TD can encapsulate a wide range of guest molecules such as CH2Cl2, CHCl3, CCl4, C6H6, and C6H5F. Interestingly, 1-TD was shown to exhibit a preferential binding of C6H5F and C6H6 over other halogenated guest molecules, as determined from NMR titrations and computational studies.

A heat-controlled release system of ethyl vanillin based on acyclic cucurbit[n]urils

Abstract Ethyl vanillin (EVA) is one of the most popular spices in the world, but it is unstable and is prone to lose its aroma. Host–Guest encapsulation by supramolecular hosts can improve stability of fragrance molecules and endow them with excellent heat-controlled release properties to satisfy requirements in food, cosmetic and tobacco, etc. Herein, two acyclic cucurbit[n]urils (ACBs, M1 and M2) inclusion complexes of EVA were prepared. Their binding behaviors were investigated by 1H NMR, SEM, XRD, FT-IR and TGA. The stoichiometric ratio was 1:1 by Job’s plot and the binding constant was determined by fluorescence titration. The intermolecular interaction between host and guest was studied by 2D-ROESY NMR and the inclusion mode was proposed. Finally, the heat-controlled release experiment indicated that the inclusion complexes of ACBs/EVA possess less volatilization at higher temperature, longer retention time and heat-controlled release. This study provides theoretical and technical guidance for expanding the application of EVA.

Chirality Induction in a Hydrophilic Metallohelicate.

The title compound is a water-soluble triply stranded metallohelicate 1Fe composed of TEG-chain-installed calix[4]arene-based bis-bidentate ligands and Fe3+ cations. This compound can incorporate up to two molecules of small chiral cations (G1 and G2). Interestingly, G1 shows positive cooperativity for host-guest complexation, whereas G2 exhibits noncooperativity, despite having a greater affinity for 1Fe than G1. Density functional theory (DFT) calculations indicate the metallohelicate cavity expands upon encapsulation of the first guest. This conformational change facilitates the entrapment of the second guest and explains why the interaction parameters of G1 and G2 are larger than 1, despite electrostatic repulsion between the guests. The DFT calculation predicts an intermolecular interaction between the phenyl groups of G1 in the cavity, whereas no such interaction is found for G2. This difference can explain the distinct molecular recognition of G1 and G2. CD spectroscopy shows that both (R)-G1 and (R)-G2 induce (M)-helicity in 1Fe and vice versa. DFT calculations suggest that the chirality of the guests is transmitted to 1Fe via CH/O hydrogen bonds between the guest and the C=O bond on the calix[4]arene strand. The CD intensity of 1Fe is nonlinear in the ee% of (R)- and (S)-G1, indicating that the presence of the first guest increases the affinity of 1Fe toward a second guest with the same chirality due to preorganization by the first guest.

Oligopyrrolic Cages: From Classic Molecular Constructs to Chemically Responsive Polytopic Receptors.

"Functional molecular systems", discrete and self-assembled constructs where control over molecular recognition, structure, bonding, transport, release, catalytic activity, etc., is readily achieved, are a topic of current interest. Within this broad paradigm, oligopyrrolic cages have garnered attention due to their responsive recognition features. Due to the presence of slightly polar pyrrole subunits which can also behave as hydrogen-bonding donors, these oligopyrrolic cages are potential receptors for various polarized species. In this Account, we summarize recent advances involving the syntheses and study of (1) covalent oligopyrrolic macrobicyclic cages, (2) oligopyrrolic metallacages, and (3) oligopyrrolic noncovalently linked cages. Considered in concert, these molecular constructs have allowed advances in applied supramolecular chemistry; to date, they have been exploited for selective guest encapsulation studies, anion binding and ion-channel formation, and gas absorption, among other applications. While key findings from others will be noted, in this Account will focus on our own contributions to the chemistry of discrete oligopyrrolic macrocycles and their use in supramolecular host-guest chemistry and sensing applications. In terms of specifics, we will detail how oligopyrrole cages with well-defined molecular geometries permit reversible guest binding under ambient conditions and how the incorporation of pyrrole subunits within larger superstructures allows effective control over anion/conjugate acid binding activity under ambient conditions. We will also provide examples that show how derivatization of these rudimentary macrocyclic cores with various sterically congested β-substituted oligopyrroles can provide entry into more complex supramolecular architectures. In addition, we will detail how hybrid systems that include heterocycles other than pyrrole, such as pyridine and naphthyridine, can be used to create self-assembled materials that show promise as gas-absorbing materials and colorimetric reversible sensors. Studies involving oligopyrrolic polymetallic cages and oligopyrrolic supramolecular cages will also be reviewed. First, we will discuss all-carbon-linked oligopyrrolic bicycles and continue on to present systems linked via amines and imines linkages. Finally, we will summarize recent work on pyrrolic cages created through the use of metal centers or various noncovalent interactions. We hope that this Account will provide researchers with an initial foundation for understanding oligopyrrolic cage chemistry, thereby allowing for further advances in the area. It is expected that the fundamental design and recognition principles made in the area of oligopyrrole cages, as exemplified by our contributions, will be of general use to researchers targeting the design of functional molecular systems. As such, we have structured this Account so as to summarize the past while setting the stage for the future.

Phosphorescent Host-Guest Complexes on the Basis of Polyhedral Oligomeric Silsesquioxane-Functionalized Metallotweezers.

Phosphorescent host-guest systems have attracted considerable attention because of their intriguing properties and diverse applications. In this study, a polyhedral oligomeric silsesquioxane-functionalized gold(III) tweezer receptor has been designed and synthesized. It is capable of sandwiching platinum(II) terpyridine compounds into its cavity with a high noncovalent binding affinity (association constants: ∼105 M-1 in chloroform). The resulting heterometallic host-guest complexes exhibit enhanced phosphorescent emission compared with those of the individual species in chloroform, thanks to the prevention of vibration and rotation upon noncovalent complexation. They can further assemble into nanospheres in chloroform/diethyl ether (1:9, v/v) owing to phase segregation between the metallotweezer/guest motif and the peripheral polyhedral oligomeric silsesquioxane unit. When terpyridine platinum(II) chloride serves as the complementary guest, the resulting noncovalent system displays an intraligand emission at the individual host-guest complexed state yet excimeric emission at the supramolecular assembled state, yielding the phosphorescent solvatochromic behaviors. Overall, the polyhedral oligomeric silsesquioxane-functionalized metallotweezer combines guest encapsulation and supramolecular assembly capabilities, which provides new avenues for color-tunable phosphorescent materials.

Guest encapsulation and self-assembly of a box-like metalla-rectangle featuring Cp*Rh fragments

A box-like metalla-rectangle with a solvophobic pocket was designed and obtained by using polyaromatic building blocks. Polyaromatic hydrocarbons were encapsulated in the pocket of the metalla-rectangle, which was evidenced by NMR spectroscopy and single crystal X-ray diffraction analysis. Besides, owing to the solvophobic property of the pocket of the metalla-rectangle, we observed binding of progesterone, a bioactive molecule with a lipophilic steroid skeleton, which was evidenced by NMR spectroscopy.

Counteranions at Peripheral Sites Tune Guest Affinity for a Protonated Hemicryptophane.

The affinity of small molecules for biomolecular cavities is tuned through a combination of primary and secondary interactions. It has been challenging to mimic these features in organic synthetic host molecules, however, where the cavities tend to be highly symmetric and nonpolar, and less amenable to chemical manipulation. Here, a host molecule composed of a TREN ligand and cyclotriveratrylene moiety was investigated. Size-matched polar guests were encapsulated within the cavity via triple protonation of the TREN moiety with various sulfonic acids. X-ray crystallography confirmed guest encapsulation and identified three methanesulfonates, p-toluenesulfonates, or 2-naphthalenesulfonates hydrogen-bonded with H3TREN at the periphery of the cavity. These structurally diverse counteranions were shown by 1H NMR spectroscopy to differentially regulate guest access at the three portals, and to undergo competitive displacement in solution. This work reveals "counteranion tuning" to be a simple and powerful strategy for modulating host-guest affinity, as applied here in a TREN-hemicryptophane.