An antiaromatic-walled nanospace.

Over the past few decades, several molecular cages, hosts and nanoporous materials enclosing nanometre-sized cavities have been reported1-5, including coordination-driven nanocages6. Such nanocages have found widespread use in molecular recognition, separation, stabilization and the promotion of unusual chemical reactions, among other applications3-10. Most of the reported nanospaces within molecular hosts are confined by aromatic walls, the properties of which help to determine the host-guest behaviour. However, cages with nanospaces surrounded by antiaromatic walls have not yet been developed, owing to the instability of antiaromatic compounds; as such, the effect of antiaromatic walls on the properties of nanospaces remains unknown. Here we demonstrate the construction of an antiaromatic-walled nanospace within a self-assembled cage composed of four metal ions with six identical antiaromatic walls. Calculations indicate that the magnetic effects of the antiaromatic moieties surrounding this nanospace reinforce each other. This prediction is confirmed by 1H nuclear magnetic resonance (NMR) signals of bound guest molecules, which are observed at chemical shift values of up to 24 parts per million (ppm), owing to the combined antiaromatic deshielding effect of the surrounding rings. This value, shifted 15 ppm from that of the free guest, is the largest 1H NMR chemical shift displacement resulting from an antiaromatic environment observed so far. This cage may thus be considered as a type of NMR shift reagent, moving guest signals well beyond the usual NMR frequency range and opening the way to further probing the effects of an antiaromatic environment on a nanospace.

Triamine and Tetramine Edge-Length Matching Drives Heteroleptic Triangular and Tetragonal Prism Assembly.

Heteroleptic metal-organic capsules, which incorporate more than one type of ligand, can provide enclosed, anisotropic interior cavities for binding low-symmetry molecules of biological and industrial importance. However, the selective self-assembly of a single mixed-ligand architecture, as opposed to the numerous other possible self-assembly outcomes, remains a challenge. Here, we develop a design strategy for the subcomponent self-assembly of heteroleptic metal-organic architectures with anisotropic internal void spaces. Zn6Tet3Tri2 triangular prismatic and Zn8Tet2Tet'4 tetragonal prismatic architectures were prepared through careful matching of the side lengths of the tritopic (Tri) or tetratopic (Tet, Tet') and panels.

Light-Driven Purification of Progesterone from Steroid Mixtures Using a Photoresponsive Metal-Organic Capsule.

Chemical separations are expensive, consuming 10-15% of humanity's global energy budget. Many current separation methods employ thermal energy for distillation, often through the combustion of carbon-containing fuels, or extractions and crystallizations from organic solvents, which must then be discarded or redistilled, with a substantial energetic cost. The direct use of renewable energy sources, such as light, could enable the development of novel separations processes, as is required for the transition away from fossil fuel use. Metal-organic capsules, which can selectively bind molecules from mixtures, can provide the foundation for these novel separations processes. Here we report a tetrahedral metal-organic capsule bearing light-responsive diazo moieties around its metal-ion vertices. This capsule can be used to selectively separate progesterone from a mixture of steroids in a process driven by visible light energy. Our process combines biphasic extraction and selective binding of progesterone with the light-driven release of this molecule in purified form. Ultimately, our process might be adapted to the purifications of the many other fine chemical products that are bound selectively by capsules.

Steric and Geometrical Frustration Generate Two Higher-Order CuI12L8 Assemblies from a Triaminotriptycene Subcomponent.

The use of copper(I) in metal-organic assemblies leads readily to the formation of simple grids and helicates, whereas higher-order structures require complex ligand designs. Here, we report the clean and selective syntheses of two complex and structurally distinct CuI12L8 frameworks, 1 and 2, which assemble from the same simple triaminotriptycene subcomponent and a formylpyridine around the CuI templates. Both represent new structure types. In T-symmetric 1, the copper(I) centers describe a pair of octahedra with a common center but whose vertices are offset from each other, whereas in D3-symmetric 2, the metal ions form a distorted hexagonal prism. The syntheses of these architectures illustrate how more intricate CuI-based complexes can be prepared via subcomponent self-assembly than has been possible to date through consideration of the interplay between the subcomponent geometry and solvent and electronic effects.

A CuI6L4 Cage Dynamically Reconfigures to Form Suit[4]anes and Selectively Bind Fluorinated Steroids.

Simple organic ligands can self-assemble with metal ions to generate metal-organic cages, whose cavities bind guests selectively. This binding may enable new methods of chemical separation or sensing, among other useful functions. Here we report the preparation of a CuI6L4 pseudo-octahedral metal-organic cage, the ligands of which self-assemble from simple organic building blocks. Temperature, solvent, and the presence of different guests governed which structure predominated from a dynamic mixture of cage diastereomers with different arrangements of right- or left-handed metal vertices. Dissolution in dimethyl sulfoxide or the binding of tetrahedral guests led to a chiral tetrahedral T-symmetric framework, whereas low temperatures favored the achiral S4-symmetric diastereomer. Tetrahedral guests with long arms were encapsulated to form mechanically bonded suit[4]anes, with guest arms protruding out through host windows. The cage was also observed to bind fluorinated steroids, an important class of drug molecules, but not non-fluorinated steroids, providing the basis for new separation processes.

Stereocontrolled Self-Assembly of a Helicate-Bridged CuI12L4 Cage That Emits Circularly Polarized Light.

Control over the stereochemistry of metal-organic cages can give rise to useful functions that are entwined with chirality, such as stereoselective guest binding and chiroptical applications. Here, we report a chiral CuI12L4 pseudo-octahedral cage that self-assembled from condensation of triaminotriptycene, aminoquinaldine, and diformylpyridine subcomponents around CuI templates. The corners of this cage consist of six head-to-tail dicopper(I) helicates whose helical chirality can be controlled by the addition of enantiopure 1,1'-bi-2-naphthol (BINOL) during the assembly process. Chiroptical and nuclear magnetic resonance (NMR) studies elucidated the process and mechanism of stereochemical information transfer from BINOL to the cage during the assembly process. Initially formed CuI(BINOL)2 thus underwent stereoselective ligand exchange during the formation of the chiral helicate corners of the cage, which determined the overall cage stereochemistry. The resulting dicopper(I) helicate corners of the cage were also shown to generate circularly polarized luminescence.

Beyond Platonic: How to Build Metal-Organic Polyhedra Capable of Binding Low-Symmetry, Information-Rich Molecular Cargoes.

The field of metallosupramolecular chemistry has advanced rapidly in recent years. Much work in this area has focused on the formation of hollow self-assembled metal-organic architectures and exploration of the applications of their confined nanospaces. These discrete, soluble structures incorporate metal ions as 'glue' to link organic ligands together into polyhedra.Most of the architectures employed thus far have been highly symmetrical, as these have been the easiest to prepare. Such high-symmetry structures contain pseudospherical cavities, and so typically bind roughly spherical guests. Biomolecules and high-value synthetic compounds are rarely isotropic, highly-symmetrical species. To bind, sense, separate, and transform such substrates, new, lower-symmetry, metal-organic cages are needed. Herein we summarize recent approaches, which taken together form the first draft of a handbook for the design of higher-complexity, lower-symmetry, self-assembled metal-organic architectures.

Metal Ions Trigger the Gelation of Cysteine-Containing Peptide-Appended Coordination Cages.

We report a series of coordination cages that incorporate peptide chains at their vertices, prepared through subcomponent self-assembly. Three distinct heterochiral tripeptide subcomponents were incorporated, each exhibiting an L-D-L stereoconfiguration. Through this approach, we prepared and characterized three tetrahedral metal-peptide cages that incorporate thiol and methylthio groups. The gelation of these cages was probed through the binding of additional metal ions, with the metal-peptide cages acting as junctions, owing to the presence of sulfur atoms on the peripheral peptides. Gels were obtained with cages bearing cysteine at the C-terminus. Our strategy for developing functional metal-coordinated supramolecular gels with a modular design may result in the development of materials useful for chemical separations or drug delivery.

Anionic Templates Drive Conversion between a ZnII9L6 Tricapped Trigonal Prism and ZnII6L4 Pseudo-Octahedra.

This work introduces the use of 8-aminoquinoline subcomponents to generate complex three-dimensional structures. Together with a tris(formylpyridine), 8-aminoquinoline condensed around ZnII templates to produce a tris(tridentate) ligand. This ligand is incorporated into either a tricapped trigonal prismatic ZnII9L6 structure or a pair of pseudo-octahedral ZnII6L4 diastereomers, with S4 and D2 symmetries. Introduction of a methyl group onto the aminoquinoline modulated the coordination sphere of ZnII, which favored the ZnII9L6 structure and disfavored the ZnII6L4 assembly. The tricapped trigonal prismatic ZnII9L6 architecture converted into a single ZnII6L4 cage diastereomer following the addition of a dianionic 4,4'-dinitrostilbene-2,2'-disulfonate guest. Four of these guests clustered tightly at the four windows of the ZnII6L4 cage, held in place through electrostatic interactions and hydrogen bonding, stabilize a single diastereomeric configuration with S4 symmetry.

Secondary Bracing Ligands Drive Heteroleptic Cuboctahedral PdII12 Cage Formation.

The structural complexity of self-assembled metal-organic capsules can be increased by incorporating two or more different ligands into a single discrete product. Such complexity can be useful, by enabling larger, less-symmetrical, or more guests to be bound. Here we describe a rational design strategy for the use of subcomponent self-assembly to selectively prepare a heteroleptic cage with a large cavity volume (2631 Å3) from simple, commercially available starting materials. Our strategy involves the initial isolation of a tris(iminopyridyl) PdII3 complex 1, which reacts with tris(pyridyl)triazine ligand 2 to form a heteroleptic sandwich-like architecture 3. The tris(iminopyridyl) ligand within 3 serves as a "brace" to control the orientations of the labile coordination sites on the PdII centers. Self-assembly of 3 with additional 2 was thus directed to generate a large PdII12 heteroleptic cuboctahedron host. This new cuboctahedron was observed to bind multiple polycyclic aromatic hydrocarbon guests simultaneously.

Hetero-Diels-Alder Reaction between Singlet Oxygen and Anthracene Drives Integrative Cage Self-Sorting.

A ZnII8L6 pseudocube containing anthracene-centered ligands, a ZnII4L'4 tetrahedron with a similar side length as the cube, and a trigonal prism ZnII6L3L'2 were formed in equilibrium from a common set of subcomponents. Hetero-Diels-Alder reaction with photogenerated singlet oxygen transformed the anthracene-containing "L" ligands into endoperoxide "LO" ones and ultimately drove the integrative self-sorting to form the trigonal prismatic cage ZnII6LO3L'2 exclusively. This ZnII6LO3L'2 structure lost dioxygen in a retro-Diels-Alder reaction after heating, which resulted in reversion to the initial ZnII8L6 + ZnII4L'4 ⇌ 2 × ZnII6L3L'2 equilibrating system. Whereas the ZnII8L6 pseudocube had a cavity too small for guest encapsulation, the ZnII6L3L'2 and ZnII6LO3L'2 trigonal prisms possessed peanut-shaped internal cavities with two isolated compartments divided by bulky anthracene panels. Guest binding was also observed to drive the equilibrating system toward exclusive formation of the ZnII6L3L'2 structure, even in the absence of reaction with singlet oxygen.

Light-Powered Reversible Guest Release and Uptake from Zn4L4 Capsules.

A strategy for light-powered guest release from a tetrahedral capsule has been developed by incorporating azobenzene units at its vertices. A new Zn4L4 tetrahedral capsule bearing 12 diazo moieties at its metal-ion vertices was prepared from a phenyldiazenyl-functionalized subcomponent and a central trialdehyde panel. Ultraviolet irradiation caused isomerization of the peripheral diazo groups from the thermodynamically preferred trans configuration to the cis form, thereby generating steric clash and resulting in cage disassembly and concomitant guest release. Visible-light irradiation drove cage re-assembly following re-isomerization of the diazo groups to the trans form, resulting in guest re-uptake. A detailed 19F NMR study elucidated how switching led to guest release: each metal vertex tolerated only one cis-azobenzene moiety, with further isomerization leading to cage disassembly.

A Diverse Array of Large Capsules Transform in Response to Stimuli.

The allosteric regulation of biomolecules, such as enzymes, enables them to adapt and alter their conformation to fit specific substrates, expressing different functionalities in response to stimuli. Different stimuli can also trigger synthetic coordination cages to change their shape, size, and nuclearity by reconfiguring the dynamic metal-ligand bonds that hold them together. Here we demonstrate an abiological system consisting of different organic subcomponents and ZnII metal ions, which can respond to simple stimuli in complex ways. A ZnII20L12 dodecahedron transforms to give a larger ZnII30L12 icosidodecahedron through subcomponent exchange, as an aldehyde that forms bidentate ligands is displaced in favor of one that forms tridentate ligands together with a penta-amine subcomponent. In the presence of a chiral template guest, the same system that produced the icosidodecahedron instead gives a ZnII15L6 truncated rhombohedral architecture through enantioselective self-assembly. Under specific crystallization conditions, a guest induces a further reconfiguration of either the ZnII30L12 or ZnII15L6 cages to yield an unprecedented ZnII20L8 pseudo-truncated octahedral structure. The transformation network of these cages shows how large synthetic hosts can undergo structural adaptation through the application of chemical stimuli, opening pathways to broader applications.

Subtle Stereochemical Effects Influence Binding and Purification Abilities of an FeII4L4 Cage.

A tetrahedral FeII4L4 cage assembled from the coordination of triangular chiral, face-capping ligands to iron(II). This cage exists as two diastereomers in solution, which differ in the stereochemistry of their metal vertices, but share the same point chirality of the ligand. The equilibrium between these cage diastereomers was subtly perturbed by guest binding. This perturbation from equilibrium correlated with the size and shape fit of the guest within the host; insight as to the interplay between stereochemistry and fit was provided by atomistic well-tempered metadynamics simulations. The understanding thus gained as to the stereochemical impact on guest binding enabled the design of a straightforward process for the resolution of the enantiomers of a racemic guest.

Quantifying the Effect of Guest Binding on Host Environment.

The environment around a host-guest complex is defined by intermolecular interactions between the complex, solvent molecules, and counterions. These interactions govern both the solubility of these complexes and the rates of reactions occurring within the host molecules and can be critical to catalytic and separation applications of host-guest systems. However, these interactions are challenging to detect using standard analytical chemistry techniques. Here, we quantify the hydration and ion pairing of a FeII4L4 coordination cage with a set of guest molecules having widely varying physicochemical properties. The impact of guest properties on host ion pairing and hydration was determined through microwave microfluidic measurements paired with principal component analysis (PCA). This analysis showed that introducing guest molecules into solution displaced counterions that were bound to the cage, and that the solvent solubility of the guest has the greatest impact on the solvent and ion-pairing dynamics surrounding the host. Specifically, we found that when we performed PCA of the measured equivalent circuit parameters and the solubility and dipole moment, we observed a high (>90%) explained variance for the first two principal components for each circuit parameter. We also observed that cage-counterion pairing is well-described by a single ion-pairing type, with a one-step reaction model independent of the type of cargo, and that the ion-pairing association constant is reduced for cargo with higher water solubility. Quantifying hydration and cage-counterion interactions is a critical step to building the next generation of design criteria for host-guest chemistries.

Self-Assembly of Double-Helical Metallopolymers.

Metal-containing polymers, or metallopolymers, have diverse applications in the fields of sensors, catalysis, information storage, optoelectronics, and neuromorphic computing, among other areas. The approach of metal-templated subcomponent self-assembly using dynamic covalent linkages allows complex architectures to be formed with relative synthetic ease. The dynamic nature of the linkages between subunits in these systems facilitates error checking during the assembly process and also provides a route to disassemble the structure, rendering these materials recyclable. This Account summarizes a class of double-helical metallopolymers. These metallopolymers are formed via subcomponent self-assembly and consist of two conjugated helical strands wrapping a linear array of CuI centers. Starting from discrete model helicates, we discuss how, through the judicious design of subcomponents, long helical metallopolymers can be obtained and detail their subsequent assembly into nanometer-scale aggregates. Two approaches to generate these helical metallopolymers are compared. We describe methods to govern (i) the length of the metallopolymers, (ii) the relative orientations (head-to-head vs head-to-tail) of the two organic strands, and (iii) the screw-sense of the double helix. Achieving structural control allowed the growth behavior of these systems to be probed. The structure influenced properties in ways that are relevant to specific applications; for example, the length of the metallopolymer determines the color of the light it emits in solution. In the solid state, the ionic nature of these helices renders them useful as both emitters and ionic additives in light-emitting electrochemical cells. Moreover, recent experimental work has clarified the role of the linear array of Cu ions in the transport of charge through these materials. The conductivity displayed by a film of metallopolymer depends upon its history of applied voltage and current, behavior characteristic of a memristor. In addition to the prospective applications already identified, others may be on the horizon, potentially combing stimuli-responsive electronic behavior with the chirality of the helical twist.

Transformation networks of metal-organic cages controlled by chemical stimuli.

The flexibility of biomolecules enables them to adapt and transform as a result of signals received from the external environment, expressing different functions in different contexts. In similar fashion, coordination cages can undergo stimuli-triggered transformations owing to the dynamic nature of the metal-ligand bonds that hold them together. Different types of stimuli can trigger dynamic reconfiguration of these metal-organic assemblies, to switch on or off desired functionalities. Such adaptable systems are of interest for applications in switchable catalysis, selective molecular recognition or as transformable materials. This review highlights recent advances in the transformation of cages using chemical stimuli, providing a catalogue of reported strategies to transform cages and thus allow the creation of new architectures. Firstly we focus on strategies for transformation through the introduction of new cage components, which trigger reconstitution of the initial set of components. Secondly we summarize conversions triggered by external stimuli such as guests, concentration, solvent or pH, highlighting the adaptation processes that coordination cages can undergo. Finally, systems capable of responding to multiple stimuli are described. Such systems constitute composite chemical networks with the potential for more complex behaviour. We aim to offer new perspectives on how to design transformation networks, in order to shed light on signal-driven transformation processes that lead to the preparation of new functional metal-organic architectures.

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

The anthracene panels of two tetrahedral MII 4 L6 cages, where MII =CoII or FeII , were found to react with photogenerated singlet oxygen (1 O2 ) 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-FeII 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 1 O2 thus served as a stimulus for guest release and reuptake.

Allosterically Regulated Guest Binding Determines Framework Symmetry for an FeII 4 L4 Cage.

Self-assembly of a flexible tritopic aniline and 3-substituted 2-formylpyridine subcomponents around iron(II) templates gave rise to a low-spin FeII 4 L4 capsule, whereas a high-spin FeII 3 L2 sandwich species formed when a sterically hindered 6-methyl-2-formylpyridine was used. The FeII 4 L4 cage adopted a new structure type with S4 symmetry, having two mer-Δ and two mer-Ʌ metal vertices, as confirmed by NMR and X-ray crystallographic analysis. The flexibility of the face-capping ligand endows the resulting FeII 4 L4 framework with conformational plasticity, enabling it to adapt structurally from S4 to T or C3 symmetry upon guest binding. The cage also displayed negative allosteric cooperativity in simultaneously binding different guests within its cavity and at the apertures between its faces.

Tetramine Aspect Ratio and Flexibility Determine Framework Symmetry for Zn8 L6 Self-Assembled Structures.

We derive design principles for the assembly of rectangular tetramines into Zn8 L6 pseudo-cubic coordination cages. Because of the rectangular, as opposed to square, geometry of the ligand panels, and the possibility of either Δ or Λ handedness of each metal center at the eight corners of the pseudo-cube, many different cage diastereomers are possible. Each of the six tetra-aniline subcomponents investigated in this work assembled with zinc(II) and 2-formylpyridine in acetonitrile into a single Zn8 L6 pseudo-cube diastereomer, however. Each product corresponded to one of four diastereomeric configurations, with T, Th , S6 or D3 symmetry. The preferred diastereomer for a given tetra-aniline subcomponent was shown to be dependent on its aspect ratio and conformational flexibility. Analysis of computationally modeled individual faces or whole pseudo-cubes provided insight as to why the observed diastereomers were favored.