Size‐Selective Encapsulation of Hydrophobic Guests by Self‐Assembled M4L6 Cobalt and Nickel Cages

Subtle differences in metal–ligand bond lengths between a series of [M₄L₆]^4? tetrahedral cages, where M=Fe^II, Co^II, or Ni^II, were observed to result in substantial differences in affinity for hydrophobic guests in water. Changing the metal ion from iron(II) to cobalt(II) or nickel(II) increases the size of the interior cavity of the cage and allows encapsulation of larger guest molecules. NMR spectroscopy was used to study the recognition properties of the iron(II) and cobalt(II) cages towards small hydrophobic guests in water, and single‐crystal X‐ray diffraction was used to study the solid‐state complexes of the iron(II) and nickel(II) cages.     

A Triphasic Sorting System: Coordination Cages in Ionic Liquids

Host–guest chemistry is usually carried out in either water or organic solvents. To investigate the utility of alternative solvents, three different coordination cages were dissolved in neat ionic liquids. By using ¹⁹F NMR spectroscopy to monitor the presence of free and bound guest molecules, all three cages were demonstrated to be stable and capable of encapsulating guests in ionic solution. Different cages were found to preferentially dissolve in different phases, allowing for the design of a triphasic sorting system. Within this system, three coordination cages, namely Fe₄L₆ 2 , Fe₈L₁₂ 3 , and Fe₄L₄ 4 , each segregated into a distinct layer. Upon the addition of a mixture of three different guests, each cage (in each separate layer) selectively bound its preferred guest.     

Guest Binding Drives Host Redistribution in Libraries of CoII4L4 Cages

Two Co^II₄L₄ tetrahedral cages prepared from similar building blocks showed contrasting host–guest properties. One cage did not bind guests, whereas the second encapsulated a series of anions, due to electronic and geometric effects. When the building blocks of both cages were present during self‐assembly, a library of five Co^II L^A _x L^B _4?x cages was formed in a statistical ratio in the absence of guests. Upon incorporation of anions able to interact preferentially with some library members, the products obtained were redistributed in favor of the best anion binders. To quantify the magnitudes of these templation effects, ESI‐MS was used to gauge the effect of each template upon library redistribution.     

Guest Exchange Mechanisms in Mono‐Metallic PdII/PtII‐Cages Based on a Tetra‐Pyridyl Calix[4]pyrrole Ligand

Planar pyridyl N‐oxides are encapsulated in mono‐metallic Pd^II/Pt^II‐cages based on a tetra‐pyridyl calix[4]pyrrole ligand. The exchange dynamics of the cage complexes are slow on both the NMR chemical shift and EXSY timescales, but encapsulation of the guests by the cages is fast on the human timescale. A “French doors” mechanism, involving the rotation of the meso‐phenyl walls of the cages, allows the passage of the planar guests. The encapsulation of quinuclidine N‐oxide, a sterically more demanding guest, is slower than pyridyl N‐oxides in the Pd^II‐cage, and does not take place in the Pt^II counterpart. A modification of the encapsulation mechanism for the quinuclidine N‐oxide is postulated that requires the partial dissociation of the Pd^II‐cage. The substrate binding selectivity featured by the cages is related to their different guest uptake/release mechanisms.     

Reversible reduction drives anion ejection and C60 binding within an FeII4L6 cage

Fe^II₄L₆ tetrahedral cage 1 was prepared from a redox-active dicationic naphthalenediimide (NDI) ligand. The +20 charge of the cage makes it a good host for anionic guests, with no binding observed for neutral aromatic molecules. Following reduction by Cp₂Co, the cage released anionic guests; subsequent oxidation by AgNTf₂ led to re-uptake of anions. In its reduced form, however, 1 was observed to bind neutral C₆₀. The fullerene guest was subsequently ejected following cage re-oxidation. The guest release process was found to be facilitated by anion-mediated transport from organic to aqueous solution. Cage 1 thus employs electron transfer as a stimulus to control the uptake and release of both neutral and charged guests, through distinct pathways.

Fe^II₄L₆ cage 1 binds anionic guests but not neutral guests. In its reduced form, the cage can bind neutral C₆₀. Reduction and oxidation of the cage could thus be used as a stimulus to control the uptake and release of both neutral and charged guests.     

Determination of NMR Lineshape Anisotropy of Guest Molecules within Inclusion Complexes from Molecular Dynamics Simulations

Nonspherical cages in inclusion compounds can result in non‐uniform motion of guest species in these cages and anisotropic lineshapes in NMR spectra of the guest. Herein, we develop a methodology to calculate lineshape anisotropy of guest species in cages based on molecular dynamics simulations of the inclusion compound. The methodology is valid for guest atoms with spin 1/2 nuclei and does not depend on the temperature and type of inclusion compound or guest species studied. As an example, the nonspherical shape of the structure I (sI) clathrate hydrate large cages leads to preferential alignment of linear CO₂ molecules in directions parallel to the two hexagonal faces of the cages. The angular distribution of the CO₂ guests in terms of a polar angle θ and azimuth angle ? and small amplitude vibrational motions in the large cage are characterized by molecular dynamics simulations at different temperatures in the stability range of the CO₂ sI clathrate. The experimental ¹³C NMR lineshapes of CO₂ guests in the large cages show a reversal of the skew between the low temperature (77 K) and the high temperature (238 K) limits of the stability of the clathrate. We determine the angular distributions of the guests in the cages by classical MD simulations of the sI clathrate and calculate the ¹³C NMR lineshapes over a range of temperatures. Good agreement between experimental lineshapes and calculated lineshapes is obtained. No assumptions regarding the nature of the guest motions in the cages are required.     

Spontaneous Resolution of an Electron‐Deficient Tetrahedral Fe4L4 cage

A highly electron‐deficient C₃‐symmetric tris(bipyridyl) ligand was prepared in four steps and used for the coordination of Fe(OTf)₂, thereby resulting in the homochiral assembly of a new family of robust tetrahedral M₄L₄ cages. This homochiral T‐symmetric cage containing a relatively large cavity of 330 ų is capable of encapsulating an anionic guest, as was determined by mass spectrometry, ¹⁹F NMR spectroscopy, and finally shown from its crystal structure. Moreover, crystallization of the cage from CH₃CN led to crystals containing both (ΔΔΔΔ and ΛΛΛΛ) enantiomers, while crystallization from CH₃OH resulted in crystals containing only the right‐handed (ΔΔΔΔ) cage. The difference in the crystal packing of the two crystal structures is discussed and a feasible explanation for the unique phenomenon among supramolecular cages—spontaneous resolution—is given.     

A Double-Walled Tetrahedron with AgI4 Vertices Binds Different Guests in Distinct Sites**

A double-walled tetrahedral metal-organic cage assembled in solution from silver(I), 2-formyl-1,8-naphthyridine, halide, and a threefold-symmetric triamine. The Ag^I₄X clusters at its vertices each bring together six naphthyridine-imine moieties, leading to a structure in which eight tritopic ligands bridge four clusters in an (Ag^I₄X)₄L₈ arrangement. Four ligands form an inner set of tetrahedron walls that are surrounded by the outer four. The cage has significant interior volume, and was observed to bind anionic guests. The structure also possesses external binding clefts, located at the edges of the cage, which bound small aromatic guests. Halide ions bound to the silver clusters were observed to exchange in a well-defined hierarchy, allowing modulation of the cavity volume. The principles uncovered here may allow for increasingly more sophisticated cages with silver-cluster vertex architectures, with post-assembly tuning of the interior cavity volume enabling targeted binding behavior.     

Tuning the Intercage Distance in Charge-Regulated Blackberry-Type Assemblies through Host–Guest Chemistry

Charged or neutral adamantane guests can be encapsulated into the cavity of cationic metal–organic M₆L₄ (bpy-cage, M=Pd^II(2,2′-bipyridine), L=2,4,6-tri(4-pyridyl)-1,3,5-triazine) cages through hydrophobic interaction. These encapsulations can provide an approach to control the net charge on the resulting cage–guest complexes and regulate their charge-dominated assembly into hollow spherical blackberry-type assemblies in dilute solutions: encapsulation of neutral guests will hardly influence their self-assembly process, including the blackberry structure size, which is directly related to the intercage distance in the assembly; whereas encapsulating negatively (positively) charged guests resulted in a shorter (longer) intercage distance with larger (smaller) assemblies formed. Therefore, the host–guest chemistry approach can be used to tune the intercage distance accurately.     

Supramolecular Coordination Cages Based on N-Heterocyclic Carbene-Gold(I) Ligands and Their Precursors: Self-Assembly,Structural Transformation and Guest-Binding Properties

The incorporation of functional groups into the cavity of discrete supramolecular coordination cages (SCCs) will bring unique functions and applications. Here, three dicarboxylate ligands (H₂ L1 Cl, H₂ L2 Cl and H₂ L3 Cl) containing N-heterocyclic carbene (NHC) precursors as linkers were introduced to construct SCCs by combining with two C₃-symmertic (CpZr)₃(μ₃-O)(μ₂-OH)₃ clusters as three-connect vertices, resulted in a series of rugby-like V₂E₃ (V=vertex, E=edge) type homoleptic cages ( SCC-1 , SCC-2 and SCC-3 ). However, V₄E₆-type tetrahedral cages ( SCC-4 and SCC-5 ), incorporating six Au-NHC moieties, were obtained when the corresponding NHC-gold(I) functionalized ligands (H₂ L1 ^Au, H₂ L2 ^Au) were applied. For the first time, we present a trackable CpZr-involved cage to cage conversion to generate a heteroleptic V₂E₃ cage ( SCC-6 ) from two homoleptic cages ( SCC-2 and SCC-5 ) with different geometries of V₂E₃ and V₄E₆. The heteroleptic assembly SCC-6 can also be formed upon a subcomponent displacement strategy. The structural transformation and reassembly processes were detected and monitored by ¹H NMR spectroscopy and electrospray-ionization mass spectrometry. The formation of heteroleptic assembly was further supported by single crystal X-ray diffraction analysis. Moreover, homoleptic cage SCC-2 possesses a trigonal bipyramidal cationic cavity allowing the encapsulation of a series of sulfonate anionic guests.     

A Water Soluble Pd2L4 Cage for Selective Binding of Neu5Ac

The sialic acid N-acetylneuraminic acid (Neu5Ac) and its derivatives are involved in many biological processes including cell-cell recognition and infection by influenza. Molecules that can recognize Neu5Ac might thus be exploited to intervene in or monitor such events. A key obstacle in this development is the sparse availability of easily prepared molecules that bind to this carbohydrate in its natural solvent; water. Here, we report that the carbohydrate binding pocket of an organic soluble [Pd₂L₄]⁴⁺ cage could be equipped with guanidinium-terminating dendrons to give the water soluble [Pd₂L₄][NO₃]₁₆ cage 7 . It was shown by means of NMR spectroscopy that 7 binds selectively to anionic monosaccharides and strongest to Neu5Ac with K_a=24 M⁻¹. The cage had low to no affinity for the thirteen neutral saccharides studied. Aided by molecular modeling, the selectivity for anionic carbohydrates such as Neu5Ac could be rationalized by the presence of charge assisted hydrogen bonds and/or the presence of a salt bridge with a guanidinium solubilizing arm of 7 . Establishing that a simple coordination cage such as 7 can already selectively bind to Neu5Ac in water paves the way to improve the stability, affinity and/or selectivity properties of M₂L₄ cages for carbohydrates and other small molecules.     

Creating Coordination‐Based Cavities in a Multiresponsive Supramolecular Gel

Creating cavities in varying levels, from molecular containers to macroscopic materials of porosity, have long been motivated for biomimetic or practical applications. Herein, we report an assembly approach to multiresponsive supramolecular gels by integrating photochromic metal–organic cages as predefined building units into the supramolecular gel skeleton, providing a new approach to create cavities in gels. Formation of discrete O‐Pd₂L₄ cages is driven by coordination between Pd²⁺ and a photochromic dithienylethene bispyridine ligand (O‐PyFDTE). In the presence of suitable solvents (DMSO or MeCN/DMSO), the O‐Pd₂L₄ cage molecules aggregate to form nanoparticles, which are further interconnected through supramolecular interactions to form a three‐dimensional (3D) gel matrix to trap a large amount of solvent molecules. Light‐induced phase and structural transformations readily occur owing to the reversible photochromic open‐ring/closed‐ring isomeric conversion of the cage units upon UV/visible light radiation. Furthermore, such Pd₂L₄ cage‐based gels show multiple reversible gel–solution transitions when thermal‐, photo‐, or mechanical stimuli are applied. Such supramolecular gels consisting of porous molecules may be developed as a new type of porous materials with different features from porous solids.     

Synthesis and Solution Studies of Silver(I)‐Assembled Porphyrin Coordination Cages

The synthesis and the characterization of two porphyrin coordination cages are reported. The design of the cage formation is based on the coordination of silver(I) ions to the pyridyl units of 3‐pyridyl appended porphyrins. ¹H/¹⁰⁹Ag NMR spectroscopy, and diffusion‐ordered spectroscopy (DOSY) experiments demonstrate that both the free base porphyrin 2H‐TPyP and the Zn‐porphyrin Zn‐TPyP form the closed cages, [ Ag₄(2H‐TPyP)₂ ]⁴⁺ and [ Ag₄(Zn‐TPyP)₂ ]⁴⁺, respectively, upon addition of two equivalents of Ag⁺. The complexation processes are characterized in details by means of absorption and emission spectroscopy in diluted CH₂Cl₂ solutions. The data are discussed in the frame of the point‐dipole exciton coupling theory; the two porphyrin monomers, in fact, experience a rigid face‐to‐face geometry in the cages and a weak inter‐porphyrin exciton coupling. An intermediate species is observed, for Zn‐TPyP , in a porphyrin/Ag⁺ stoichiometric ratio of about 1:0.5 and is tentatively ascribed to an oblique open form. The occurrence of a photoinduced electron‐transfer reaction within the cages is excluded on the basis of the experimental outcomes and thermodynamic evaluations. Photophysical experiments evidence different reactivities of singlet and triplet excited states in the assemblies. A lower fluorescence quantum yield and triplet formation is discussed in relation to the constrained geometry of the complexes. Unusually long triplet excited state lifetimes are measured for the assemblies.     

A Reduced-Symmetry Heterobimetallic [PdPtL4]4+ Cage: Assembly,Guest Binding,and Stimulus-Induced Switching

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL₄]⁴⁺ cage. The presence of two different metal ions (Pd^II and Pt^II) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert Pt^II tetrapyridylaldehyde complex with a suitably substituted pyridylamine and Pd^II ions led to the assembly of the cage. ¹H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single-crystal X-ray crystallography. The structure of the host–guest adduct with a 2,6-diaminoanthraquinone guest molecule was determined. Addition of N,N′-dimethylaminopyridine (DMAP) resulted in the formation of the open-cage [PtL₄]²⁺ compound and [Pd(DMAP)₄]²⁺ complex. This process could then be reversed, with the reformation of the cage, upon addition of p-toluenesulfonic acid (TsOH).     

A Reduced‐Symmetry Heterobimetallic [PdPtL4]4+ Cage: Assembly,Guest Binding,and Stimulus‐Induced Switching

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL₄]⁴⁺ cage. The presence of two different metal ions (Pd^II and Pt^II) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert Pt^II tetrapyridylaldehyde complex with a suitably substituted pyridylamine and Pd^II ions led to the assembly of the cage. ¹H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single‐crystal X‐ray crystallography. The structure of the host–guest adduct with a 2,6‐diaminoanthraquinone guest molecule was determined. Addition of N,N′‐dimethylaminopyridine (DMAP) resulted in the formation of the open‐cage [PtL₄]²⁺ compound and [Pd(DMAP)₄]²⁺ complex. This process could then be reversed, with the reformation of the cage, upon addition of p‐toluenesulfonic acid (TsOH).     

An atropisomeric M2L4 cage mixture displaying guest-induced convergence and strong guest emission in water

Introduction of atropisomeric axes into a bent bispyridine ligand leads to the quantitative formation of a complex mixture of atropisomeric M₂L₄ cages upon treatment with metal ions. Whereas the isomer ratio of the obtained cage mixture, consisting of up to 42 isomers, is insensitive to temperature and solvent, the quantitative convergence from the mixture to a single isomer is accomplished upon encapsulation of a large spherical guest, namely fullerene C₆₀. The observed isomerization with other guests depends largely on their size and shape (e.g., <10 and 82% convergence with planar triphenylene and bowl-shaped corannulene guests, respectively). Besides the unusual guest-induced convergence, the present cage mixture displays the strongest guest emission (Φ_F = 68%) among previously reported M_nL_m cages and capsules, upon encapsulation of a BODIPY dye in water.

A complex mixture of atropisomeric M₂L₄ cages is shown to undergo perfect convergence to a single isomer upon encapsulation of spherical C₆₀ in water. Moreover, the cage mixture displays very strong guest emission upon encapsulation of a BODIPY dye.     

Chiral Self‐Discrimination and Guest Recognition in Helicene‐Based Coordination Cages

Chiral nanosized confinements play a major role for enantioselective recognition and reaction control in biological systems. Supramolecular self‐assembly gives access to artificial mimics with tunable sizes and properties. Herein, a new family of [Pd₂L₄] coordination cages based on a chiral [6]helicene backbone is introduced. A racemic mixture of the bis‐monodentate pyridyl ligand L¹ selectively assembles with Pd^II cations under chiral self‐discrimination to an achiral meso cage, cis‐[Pd₂ L^1P ₂ L^1M ₂]. Enantiopure L¹ forms homochiral cages [Pd₂ L^1P/M ₄]. A longer derivative L² forms chiral cages [Pd₂ L^2P/M ₄] with larger cavities, which bind optical isomers of chiral guests with different affinities. Owing to its distinct chiroptical properties, this cage can distinguish non‐chiral guests of different lengths, as they were found to squeeze or elongate the cavity under modulation of the helical pitch of the helicenes. The CD spectroscopic results were supported by ion mobility mass spectrometry.     

Capture of Singlet Oxygen Modulates Host-Guest Behavior of Coordination Cages

The anthracene panels of two tetrahedral M^II₄L₆ cages, where M^II=Co^II or Fe^II, were found to react with photogenerated singlet oxygen (¹O₂) in a hetero-Diels–Alder reaction. ESI-MS analysis showed the cobalt(II) cages to undergo complete transformation of all anthracene panels into endoperoxides, whereas the iron(II) congeners underwent incomplete conversion. The reaction was found to be partially reversible in the case of the 1-Fe^II cage. The dioxygen-cage cycloadducts were found to bind a set of guest molecules more weakly than the parent cages, with affinity dropping by more than two orders of magnitude in some cases. The light-driven cycloaddition reaction between cage and ¹O₂ thus served as a stimulus for guest release and reuptake.     

An Octanuclear Metallosupramolecular Cage Designed To Exhibit Spin‐Crossover Behavior

By employing the subcomponent self‐assembly approach utilizing 5,10,15,20‐tetrakis(4‐aminophenyl)porphyrin or its zinc(II) complex, 1H ‐4‐imidazolecarbaldehyde, and either zinc(II) or iron(II) salts, we were able to prepare O‐symmetric cages having a confined volume of ca. 1300 ų. The use of iron(II) salts yielded coordination cages in the high‐spin state at room temperature, manifesting spin‐crossover in solution at low temperatures, whereas corresponding zinc(II) salts led to the corresponding diamagnetic analogues. The new cages were characterized by synchrotron X‐ray crystallography, high‐resolution mass spectrometry, and NMR, Mössbauer, IR, and UV/Vis spectroscopy. The cage structures and UV/Vis spectra were independently confirmed by state‐of‐the‐art DFT calculations. A remarkably high‐spin‐stabilizing effect through encapsulation of C₇₀ was observed. The spin‐transition temperature T _1/2 is lowered by 20 K in the host–guest complex.     

Selective Encapsulation and Sequential Release of Guests Within a Self‐Sorting Mixture of Three Tetrahedral Cages

A mixture of two triamines, one diamine, 2‐formylpyridine and a Zn^II salt was found to self‐sort, cleanly producing a mixture of three different tetrahedral cages. Each cage bound one of three guests selectively. These guests could be released in a specific sequence following the addition of 4‐methoxyaniline, which reacted with the cages, opening each in turn and releasing its guest. The system here described thus behaved in an organized way in three distinct contexts: cage formation, guest encapsulation, and guest release. Such behavior could be used in the context of a more complex system, where released guests serve as signals to other chemical actors.