Guest Encapsulation Research Articles

Interplay of Stereochemistry and Charge Governs Guest Binding in Flexible ZnII4L4 Cages.

Here, we report the synthesis of a family of chiral ZnII4L4 tetrahedral cages by subcomponent self-assembly. These cages contain a flexible trialdehyde subcomponent that allows them to adopt stereochemically distinct configurations. The incorporation of enantiopure 1-phenylethylamine produced Δ4 and Λ4 enantiopure cages, in contrast to the racemates that resulted from the incorporation of achiral 4-methoxyaniline. The stereochemistry of these ZnII4L4 tetrahedra was characterized by X-ray crystallography and chiroptical spectroscopy. Upon binding the enantiopure natural product podocarpic acid, the ZnII stereocenters of the enantiopure Δ4-ZnII4L4 cage retained their Δ handedness. In contrast, the metal stereocenters of the enantiomeric Λ4-ZnII4L4 cage underwent inversion to a Δ configuration upon encapsulation of the same guest. Insights gained about the stereochemical communication between host and guest enabled the design of a process for acid/base-responsive guest uptake and release, which could be followed by chiroptical spectroscopy.

Structure Elucidation of Pharmaceutically Relevant Compounds Within Pyrene-Based Frameworks.

Single-crystal X-ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules and active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or can be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G4PYR), a robust guanidinium-organosulfonate (GS) framework that efficiently encapsulates small molecules and APIs rich in functional groups. The hydrogen bonding frameworks formed by G4PYR display well-ordered structures with predictable pyrene-pyrene distances, making them ideally suited for targeting arene-based APIs with pendant groups. Successful encapsulation of various guests, including benzaldehyde, benzamide, and arenes containing multiple hydrogen bond donors and acceptors like uracil and thymine, was achieved. Furthermore, we successfully encapsulated important pharmaceutical and biologically relevant compounds, such as lidocaine, ropinirole, adenosine, thymidine, and others. Notably, we present a workflow for investigating host-guest complex formation using powder X-ray diffraction and high throughput experimentation.

Ligand‐Directed Synthesis of a Self‐Organized Chloro‐Bridged Cubic Pd(II) Cage Showing Selective Encapsulation of Phenols

AbstractThe synthesis and guest recognition properties of a neutral Pd24‐cubic cage, [{Pd3(NiPr)3PO}8(μ2‐Cl)24] 1 are reported. The formation of the cubical assembly takes place by an exclusive one‐pot ligand‐assisted pathway directed by an oximido linker. The initial coordination of the oximido ligand pre‐organizes the [Pd3(NiPr)3PO]3+ polyhedral building units into a tetrameric intermediate, which then transforms into an oximido‐tethered tetrahedral assembly and to the cubical cage 1 in the presence of chloride ions. In the absence of the directing oximido linker, no cage formation was observed, and the Pd6‐precursor was found to undergo self‐condensation, giving rise to a new pentameric polyhedral cluster, [Pd5{(NiPr)3PO}2(OAc)2(OH)2] 2. The central cavity of the cube has been probed for guest encapsulation studies, which shows a high binding with phenolic guest molecules with association constants of the order of 104–105 M−1. The favorable formation of host–guest complexes was attributed to the strong hydrogen bonding interactions between the host and guest functional groups.

Ligand-Directed Synthesis of a Self-Organized Chloro-Bridged Cubic Pd(II) Cage Showing Selective Encapsulation of Phenols.

The synthesis and guest recognition properties of a neutral Pd24-cubic cage, [{Pd3(NiPr)3PO}8(μ2-Cl)24] 1 are reported. The formation of the cubical assembly takes place by an exclusive one-pot ligand-assisted pathway directed by an oximido linker. The initial coordination of the oximido ligand pre-organizes the [Pd3(NiPr)3PO]3+ polyhedral building units into a tetrameric intermediate, which then transforms into an oximido-tethered tetrahedral assembly and to the cubical cage 1 in the presence of chloride ions. In the absence of the directing oximido linker, no cage formation was observed, and the Pd6-precursor was found to undergo self-condensation, giving rise to a new pentameric polyhedral cluster, [Pd5{(NiPr)3PO}2(OAc)2(OH)2] 2. The central cavity of the cube has been probed for guest encapsulation studies, which shows a high binding with phenolic guest molecules with association constants of the order of 104-105 M-1. The favorable formation of host-guest complexes was attributed to the strong hydrogen bonding interactions between the host and guest functional groups.

Preparation of Zn-based MOFs photoluminescent coatings on cotton fabrics and their application in anti-counterfeiting

In this paper, a series of new photoluminescent coatings on cotton fabrics were prepared by integrating Zn-based MOFs (ZnBDC), and ZnBDC was encapsulated with luminescent guests (Eu3+ and crystal violet (CV)). The results showed that a large amount of ZnBDC nanomaterials could effectively grow on cotton fabric, and the encapsulation of luminescent guests did not damage their structural integrity and morphology. The emission spectra of different encapsulated samples exhibited different fluorescence under excitation at 321 nm. Notably, different from the single Eu3+ emission observed in single Eu3+-encapsulated ZnBDC cotton fabric, the emission intensity of Eu3+ in dual (Eu3+ and CV) encapsulated sample changed significantly at different bands, and it dominated by an unusual 5D0 → 7F4 transition (693 nm). The transformation of a specific symmetric site of Eu3+ is responsible for this unusual emission. Moreover, the fluorescence color of encapsulated samples could be coded by regulating the concentration of encapsulated CV according to the special features of Eu3+ photoluminescence. Therefore, photoluminescent cotton fabrics have a potential application in the anti-counterfeiting of textiles.

The Delayed Box: Biphenyl Bisimide Cyclophane, a Supramolecular Nano-environment for the Efficient Generation of Delayed Fluorescence.

Activating delayed fluorescence emission in a dilute solution via a non-covalent approach is a formidable challenge. In this report, we propose a strategy for efficient delayed fluorescence generation in dilute solution using a non-covalent approach via supramolecularly engineered cyclophane-based nanoenvironments that provide sufficient binding strength to π-conjugated guests and that can stabilize triplet excitons by reducing vibrational dissipation and lowering the singlet-triplet energy gap for efficient delayed fluorescence emission. Toward this goal, a novel biphenyl bisimide-derived cyclophane is introduced as an electron-deficient and efficient triplet-generating host. Upon encapsulation of various carbazole-derived guests inside the nanocavity of this cyclophane, emissive charge transfer (CT) states close to the triplet energy level of the biphenyl bisimide are generated. The experimental results of host-guest studies manifest high association constants up to 104 M-1 as the prerequisite for inclusion complex formation, the generation of emissive CT states, and triplet-state stabilization in a diluted solution state. By means of different carbazole guest molecules, we could realize tunable delayed fluorescence emission in this carbazole-encapsulated biphenyl bisimide cyclophane in methylcyclohexane/carbon tetrachloride solutions with a quantum yield (QY) of up to 15.6%. Crystal structure analyses and solid-state photophysical studies validate the conclusions from our solution studies and provide insights into the delayed fluorescence emission mechanism.

Cooperative Binding and Chirogenesis in an Expanded Perylene Bisimide Cyclophane.

The encapsulation of more than one guest molecule into a synthetic cavity is a highly desirable yet a highly challenging task to achieve for neutral supramolecular hosts in organic media. Herein, we report a neutral perylene bisimide cyclophane, which has a tailored chiral cavity with an interchromophoric distance of 11.2 Å, capable of binding two aromatic guests in a π-stacked fashion. Detailed host-guest binding studies with a series of aromatic guests revealed that the encapsulation of the second guest in this cyclophane is notably more favored than the first one. Accordingly, for the encapsulation of the coronene dimer, a cooperativity factor (α) as high as 485 was observed, which is remarkably high for neutral host-guest systems. Furthermore, a successful chirality transfer, from the chiral host to encapsulated coronenes, resulted in a chiral charge-transfer (CT) complex and the rare observation of circularly polarized emission originating from the CT state for a noncovalent donor-acceptor assembly in solution. The involvement of the CT state also afforded an enhancement in the luminescence dissymmetry factor (glum) value due to its relatively large magnetic transition dipole moment. The 1:2 binding pattern and chirality-transfer were unambiguously verified by single-crystal X-ray diffraction analysis of the host-guest superstructures.

Isoreticular Covalent Organic Pillars: Engineered Nanotubular Hosts for Tailored Molecular Recognition.

In the realm of nanoscale materials design, achieving precise control over the dimensions of nanotubular architectures poses a substantial challenge. In our ongoing pursuit, we have successfully engineered a novel class of single-molecule nanotubes─isoreticular covalent organic pillars (iCOPs)─by stacking formylated macrocycles through multiple dynamic covalent imine bonds, guided by principles of reticular chemistry. Our strategic selection of rigid diamine linkers has facilitated the synthesis of a diverse array of iCOPs, each retaining a homologous structure yet offering distinct cavity shapes influenced by the linker choice. Notably, three of these iCOP variants feature continuous one-dimensional channels, exhibiting length-dependent host-guest interactions with α,ω-dibromoalkanes, and each presenting a distinct critical guest alkyl chain length threshold for efficient guest encapsulation. This newfound capability not only provides a platform for tailoring nanotubular structures with precision, but also opens new avenues for innovative applications in molecular recognition and the purification of complex mixtures.

Performance of Particle Swarm Optimization in Predicting the Orientation of π-Conjugated Molecules Inside Carbon Nanotubes Compared with Density Functional Theory Calculations.

Particle swarm optimization (PSO) was employed to obtain the global minimum of host-guest structures consisting of a triiodobenzene molecule (BzI3) inside an armchair (m,m) nanotube (BzI3@(m,m)), whose host-guest interactions are approximated by Lennard-Jones (LJ) potentials. The host-guest structures obtained using the PSO-LJ method were then compared with those obtained through dispersion-corrected density functional theory (DFT) calculations to evaluate the performance of the PSO-LJ approach in predicting the guest orientation inside a tube. When the inner space of the host tube is limited for guest encapsulation, the PSO-LJ method can reproduce the DFT results of BzI3@(m,m) in terms of the guest orientation. Conversely, in nanotubes with a sufficiently large space to allow a guest to freely move, corresponding to weak tube confinement, the PSO-LJ method yields guest orientations that are different from those obtained through DFT calculations; however, both methods obtain energetically close guest orientations. Accordingly, PSO-LJ method-assisted DFT calculations can quickly provide energetically stable guest orientations in BzI3@(m,m) in weak tube confinement, which can be ignored in DFT calculations, where a single initial geometry is typically used.

Vesicle-like Nanocapsules Formed by Self-Assembly of Peptides with Oligoproline and -Leucine.

Since drug carriers are envisaged to be used in a wide variety of situations and environments, nanocarriers with diverse properties, such as biocompatibility, biodegradability, nonimmunogenicity, adequate particle size, robustness, and cell permeability, are required. Here, we report the construction of novel nanocapsules with the above-mentioned features by the self-assembly of peptides composed of oligoproline and oligoleucine (i.e., H-Pro10Leu4-NH2 and H-Pro10Leu6-NH2). The peptides self-organized via hydrogen bonds and hydrophobic interactions between oligoleucine moieties to form vesicle-like nanocapsules with cationic oligoproline exposed on the surface. The guest encapsulation experiments revealed that the nanocapsules were capable of uptake of both water-soluble and insoluble compounds. Furthermore, positively charged and/or oligoproline-based peptides are known to improve cell permeability and cellular uptake, suggesting that the peptide nanocapsules are good candidates for nanocarriers to complement liposomes and polymer micelles.

Probing noncovalent binding, spectroscopic characteristics and antiproliferative behavior of inclusion complex between quinoline and para-sulfonatothiacalix[4]arene

The inclusion complex between bowl-shaped para-sulfonatothiacalix[4]arene (TSCX4) macrocycle and quinoline has been studied with a unison of UV–visible, infra-red, flourescence emission and 1H nuclear magnetic resonance (NMR) and 2D nuclear overhauser effect spectroscopy (NOESY), high resolution mass spectrometry (HRMS) experiments. Both 1H NMR titration and HRMS experiments point to 1:1 stoichiometry for the water soluble Q⊂TSCX4 complex. The electronic structure of the inclusion complex obtained from density functional theory (DFT) showed a partial encapsulation of quinoline guest, which is held within the host cavity by C–H---π, π---π and hydrogen bonding interactions. The fluorescence emission spectra upon complexation display marginal blue shift of the 411 nm band in TSCX4. Moreover, the binding constant (7.1 × 103 M−1) determined from fluoresence emission experiments underline the effective host–guest binding in the complex, which was corroborated through frequency up-shift (‘blue shift’) of characteristic Ar-OH (3433 cm−1) and SO3- vibrations (1141 cm−1 and 1037 cm−1) in the measured infrared spectra of TSCX4. The antiproliferative activitities of the Q⊂TSCX4 complex against HeLA, MDA-MB-231and N2a cells are presented. The Q⊂TSCX4 complex has been shown to be efficient against N2a (neuroblastoma) cell line.

Stimuli-responsive azo-functionalized non-ionic amphiphiles for controlled drug delivery applications

A series of stimuli-responsive non-ionic amphiphiles have been synthesized consisting of n-alkyl/fluoroalkyl chain to impart lipophilicity, and lactose/polyethylene glycol units which confers hydrophilicity. To execute the release of encapsulated guest in a controlled manner, the azo and ester functionalities were incorporated in the synthesized amphiphiles. The ability of the azo unit to undergo trans–cis-trans spatiotemporal isomerization under UV irradiation with subsequent release of the encapsulated guest has been studied in the aqueous solution of amphiphiles at 365 and 254 nm. Furthermore, an immobilized enzyme Candida antarctica lipase (Novozym 435), a hydrolase, was observed to facilitate the cleavage of the ester moiety of the synthesized amphiphiles resulting in the gradual collapse of the nano-aggregates and subsequent release of encapsulated guest. The aggregation and guest encapsulation behaviour of synthesized azo-functionalized amphiphiles were studied by dynamic light scattering (DLS), critical micelle concentration (CMC), and transmission electron microscopy, fluorescence and UV–Vis spectroscopy. Entrapment of hydrophobic drug/dye i.e. curcumin/Nile red in the lipophilic core, their cellular uptake, and consequently the stimuli responsive release of payload demonstrated the potential of these nanostructures in controlled drug delivery applications.

Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

Large and Tunable Wavelength Blue Shifts in Luminescent Piezochromism of Cu(I) Complexes via a Guest Encapsulation Strategy

Large and Tunable Wavelength Blue Shifts in Luminescent Piezochromism of Cu(I) Complexes via a Guest Encapsulation Strategy

54 K Spin Transition Temperature Shift in a Fe6L4 Octahedral Cage Induced by Optimal Fitted Multiple Guests.

Spin-crossover (SCO) coordination cages are at the forefront of research for their potential in crafting next-generation molecular devices. However, due to the scarcity of SCO hosts and their own limited cavities, the interplay between the SCO host and the multiple guests binding has remained elusive. In this contribution, we present a family of pseudo-octahedral coordination cages (M6L4, M = ZnII, CoII, FeII, and NiII) assembled from a tritopic tridentate ligand L with metal ions. The utilization of FeII ion leads to the successful creation of the Fe6L4-type SCO cage. Host-guest studies of these M6L4 cages reveal their capacity to encapsulate four adamantine-based guests. Notably, the spin transition temperature T1/2 of Fe6L4 is dependent on the multiple guests encapsulated. The inclusion of adamantine yields an unprecedented T1/2 shift of 54 K, a record shift in guest-mediated SCO coordination cages to date. This drastic shift is ascribed to the synergistic effect of multiple guests coupled with their optimal fit within the host. Through a straightforward thermodynamic cycle, the binding affinities of the high-spin (HS) and low-spin (LS) states are separated from their apparent binding constant. This result indicates that the LS state has a stronger binding affinity for the multiple guests than the HS state. Exploring the SCO thermodynamics of host-guest complexes allows us to examine the optimal fit of multiple guests to the host cavity. This study reveals that the T1/2 of the SCO host can be manipulated by the encapsulation of multiple guests, and the SCO cage is an ideal candidate for determining the multiple guest fit.

Dual-controlled guest release from coordination cages

Despite having significant applications in the construction of controlled delivery systems with high anti-interference capability, to our knowledge dual-controlled molecular release has not yet been achieved based on small molecular/supramolecular entities. Herein, we report a dual-controlled release system based on coordination cages, for which releasing the guest from the cage demands synchronously altering the coordinative metal cations and the solvent. The cages, Hg5L2 and Ag5L2, are constructed via coordination-driven self-assembly of a corannulene-based ligand. While Hg5L2 shows a solvent-independent guest encapsulation in all the studied solvents, Ag5L2 is able to encapsulate the guests in only some of the solvents, such as acetone-d6, but will liberate the encapsulated guests in 1,1,2,2-tetrachloroethane-d2. Hg5L2 and Ag5L2 are interconvertible. Thus, the release of guests from Hg5L2 in acetone-d6 can be achieved, but requires two separate operations, including metal substitutions and a change of the solvent. Dual-controlled systems as such could be useful in complicated molecular release process to avoid those undesired stimulus-responses.

Guest‐Facilitated Heteroleptic Assembly of Helical Anionocages Enables Reversible Chirality Modulation

AbstractWe report a novel strategy for reversible modulation of the supramolecular chirality based on guest‐facilitated heteroleptic assembly of helical anionocages. Two triple‐stranded helical anionocages including a chiral cage 1 (A2L13) and a crown ether functionalized achiral cage 2 (A2L23) were synthesized by anion coordination of bis‐monourea‐based ligands and PhPO32−. Both cages exhibited favorable binding with tetraethylammonium TEA+ and cobaltocenium Cob+ (endo‐guest, bound in the cavity). Additionally, cage 2 could reversibly release and recapture the guests through binding the exo‐guest potassium ions (K+) in the crown ethers and subsequent removal of the K+ by [2,2,2]‐cryptand. The circular dichroism (CD) spectrum of cage 1 was not significantly affected by guest encapsulation or mixing with the “empty” cage 2. However, in the presence of both cage 2 and an endo‐guest/exo‐guest, the Cotton effects were reversed at 391 nm and significantly enhanced at 310 nm. This observation was attributed to the guest‐facilitated formation of heteroleptic cages that enabled effective chirality transfer from the chiral to the achiral ligands. The CD changes induced by K+ could be fully reversed by removing it with [2,2,2]‐cryptand. Sequential addition and removal of K+ allowed reversible modulation of the chirality for at least 10 cycles without significant attenuation.

Guest-Facilitated Heteroleptic Assembly of Helical Anionocages Enables Reversible Chirality Modulation.

We report a novel strategy for reversible modulation of the supramolecular chirality based on guest-facilitated heteroleptic assembly of helical anionocages. Two triple-stranded helical anionocages including a chiral cage 1 (A2 L1 3 ) and a crown ether functionalized achiral cage 2 (A2 L2 3 ) were synthesized by anion coordination of bis-monourea-based ligands and PhPO3 2- . Both cages exhibited favorable binding with tetraethylammonium TEA+ and cobaltocenium Cob+ (endo-guest, bound in the cavity). Additionally, cage 2 could reversibly release and recapture the guests through binding the exo-guest potassium ions (K+ ) in the crown ethers and subsequent removal of the K+ by [2,2,2]-cryptand. The circular dichroism (CD) spectrum of cage 1 was not significantly affected by guest encapsulation or mixing with the "empty" cage 2. However, in the presence of both cage 2 and an endo-guest/exo-guest, the Cotton effects were reversed at 391 nm and significantly enhanced at 310 nm. This observation was attributed to the guest-facilitated formation of heteroleptic cages that enabled effective chirality transfer from the chiral to the achiral ligands. The CD changes induced by K+ could be fully reversed by removing it with [2,2,2]-cryptand. Sequential addition and removal of K+ allowed reversible modulation of the chirality for at least 10 cycles without significant attenuation.

Atomic-resolution structure analysis inside an adaptable porous framework

We introduce a versatile metal-organic framework (MOF) for encapsulation and immobilization of various guests using highly ordered internal water network. The unique water-mediated entrapment mechanism is applied for structural elucidation of 14 bioactive compounds, including 3 natural product intermediates whose 3D structures are clarified. The single-crystal X-ray diffraction analysis reveals that incorporated guests are surrounded by hydrogen-bonded water networks inside the pores, which uniquely adapt to each molecule, providing clearly defined crystallographic sites. The calculations of host-solvent-guest structures show that the guests are primarily interacting with the MOF through weak dispersion forces. In contrast, the coordination and hydrogen bonds contribute less to the total stabilization energy, however, they provide highly directional point interactions, which help align the guests inside the pore.

M(II) effect on encapsulation of guests into a series of M3L2 chiral cages: enantio-recognition.

Self-assembly of M(ClO4)2 (M2+ = Ni2+, Cu2+, and Zn2+) with (1S,1'S,1''S,2R,2'R,2''R)-(benzenetricarbonyltris(azanediyl))tris(2,3-dihydro-1H-indene-2,1-diyl) trinicotinate (s,r-L) and the corresponding enantiomer (r,s-L) as a pair of chiral tridentate donors gives rise to the chiral cage pairs [M3(s,r- and r,s-L)2](ClO4)6. For the two pairs of [(Me2CO)(H2O)@M3(r,-s and s,r-L)2](ClO4)6 (M2+ = Ni2+ and Zn2+), the inner cavity is occupied by both an acetone and a single water molecule, whereas for the copper(II) pair of [Me2CO@Cu3(r,s- and s,r-L)2](ClO4)6 under the same conditions, the cavity is filled by only one acetone molecule. Thus, the encapsulation of guest molecules into the cages during self-assembly shows significant metal(II) ion effects. These chiral cages are effective for the enantio-recognition of chiral (S)-2-butanol and (R)-2-butanol via the shifts of the electrochemical oxidation potentials obtained by the linear sweep voltammetry (LSV) technique, density functional theory (DFT) calculations, and the chiral 2-butanol adsorption in the single-crystal-to-single-crystal (SCSC) mode.