Design and Applications of Water-Soluble Coordination Cages.

Compartmentalization of the aqueous space within a cell is necessary for life. In similar fashion to the nanometer-scale compartments in living systems, synthetic water-soluble coordination cages (WSCCs) can isolate guest molecules and host chemical transformations. Such cages thus show promise in biological, medical, environmental, and industrial domains. This review highlights examples of three-dimensional synthetic WSCCs, offering perspectives so as to enhance their design and applications. Strategies are presented that address key challenges for the preparation of coordination cages that are soluble and stable in water. The peculiarities of guest binding in aqueous media are examined, highlighting amplified binding in water, changing guest properties, and the recognition of specific molecular targets. The properties of WSCC hosts associated with biomedical applications, and their use as vessels to carry out chemical reactions in water, are also presented. These examples sketch a blueprint for the preparation of new metal-organic containers for use in aqueous solution, as well as guidelines for the engineering of new applications in water.

Fluorometric Recognition of Nucleotides within a Water-Soluble Tetrahedral Capsule.

The design of aqueous probes and binders for complex, biologically relevant anions presents a key challenge in supramolecular chemistry. Herein, a tetrahedral assembly with cationic faces and corners is reported that is capable of discriminating between anionic and neutral guests in water. Electrostatic repulsion between subcomponents can be overcome by the addition of an anionic template, or generating a robust covalent framework by incorporating tris(2-aminoethyl)amine (TREN). The resultant TREN-capped, water-soluble, fluorescent cage binds mono- and poly-phosphoric esters, including nucleotides. Its covalent skeleton renders it stable at micromolar concentrations in water, enabling the fluorometric detection of biologically relevant guests in an aqueous environment. Selective supramolecular encapsulants, such as 1, could enable new sensing applications, such as recognition of toxins and drugs, under biological conditions.

Anion Exchange Drives Reversible Phase Transfer of Coordination Cages and Their Cargoes.

Chemical separations technologies are energetically costly; lowering this cost through the development of new molecular separation methods would thus enable significant energy savings. Molecules could, for example, be selectively encapsulated and separated using coordination cages, which can be designed with cavities of tailored sizes and geometries. Before cages can be used to perform industrially relevant separations, however, the experimental and theoretical foundations for this technology must be established. Using hydrophobic and hydrophilic anions as stimuli, we show that cages can reversibly transfer many times between mutually immiscible liquid phases, thus transporting their molecular cargoes over macroscopic distances. Furthermore, when two cages are dissolved together, sequential phase transfer of individual cage species results in the separation of their molecular cargoes. We present a thermodynamic model that describes the transfer profiles of these cages, both individually and in the presence of other cage species. This model provides a new analytical tool to quantify the hydrophobicity of cages.

Anion Exchange Renders Hydrophobic Capsules and Cargoes Water-Soluble.

Control over the solubility properties of container molecules is a central challenge in host-guest chemistry. Herein we present a simple anion-exchange protocol that allows the dissolution in water of various hydrophobic metal-organic container molecules prepared by iron(II)-templated subcomponent self-assembly. Our process involved the exchange of less hydrophilic trifluoromethanesulfonate anions for hydrophilic sulfate; the resulting water-soluble cages could be rendered water-insoluble through reverse anion exchange. Notably, this strategy allowed cargoes within capsules, including polycyclic aromatic compounds and complex organic drugs, to be brought into water. Hydrophobic effects appeared to enhance binding, as many of these cargoes were not bound in non-aqueous media. Studies of the scope of this method revealed that cages containing tetratopic and tritopic ligands were more stable in water, whereas cages with ditopic ligands disassembled.

Metal-organic cages against toxic chemicals and pollutants.

The continuous release of toxic chemicals and pollutants into the atmosphere and natural waters threatens, directly and indirectly, human health, the sustainability of the planet, and the future of society. Materials capable of capturing or chemically inactivating hazardous substances, which are harmful to humans and the environment, are critical in the modern age. Metal-organic cages (MOCs) show great promise as materials against harmful agents both in solution and in solid state. This Highlight features examples of MOCs that selectively encapsulate, adsorb, or remove from a medium noxious gases, toxic organophosphorus compounds, water pollutant oxoanions, and some emerging organic contaminants. Remarkably, the toxicity of interacting contaminants may be lowered by MOCs as well. Specific cases pertaining to the use of these cages for the chemical degradation of some harmful substances are presented. This Highlight thus aims to provide an overview of the possibilities of MOCs in this area and new methodological insights into their operation for enhancing their activity and the engineering of further remediation applications.

Sc(III)-Based metal-organic frameworks.

Scandium(III) ions can form robust metal-organic frameworks (MOFs) with relative ease of synthesis. However, their use in MOF construction remains scarce compared to the vast collection of MOFs using other ions. This highlight features the chronological development of Sc(III)-MOFs, which attest to the ability of Sc(III) ions to afford materials that combine exceptional stability with catalytic or photo-physical attributes.

SO2 Capture and Oxidation in a Pd6L8 Metal-Organic Cage.

The facile and green preparation of novel materials that capture sulfur dioxide (SO2) with significant uptake at room temperature remains challenging, but it is crucial for public health and the environment. Herein, we explored for the first time the SO2 adsorption within microporous metal-organic cages using the palladium(II)-based [Pd6L8](NO3)36 tetragonal prism 1, assembled in water under mild conditions. Notably and despite the low BET surface area of 1 (111 m2 g-1), sulfur dioxide was found to be irreversibly and strongly adsorbed within the activated cage at 298 K (up to 6.07 mmol g-1). The measured values for the molar enthalpy of adsorption (ΔHads) coupled to the FTIR analyses imply a chemisorption process that involves the direct interaction of SO2 with Pd(II) sites and the subsequent oxidation of this toxic chemical by the action of the nitrate anions in 1. To the best of our knowledge, this is the first reported metal-organic cage that proves useful for SO2 adsorption. Metallosupramolecular adsorbents such as 1 could enable new detection applications and suggest that the integration of soft metal ions and self-assembly of molecular cages are a potential means for the easy tuning of SO2 adsorption capabilities and behavior.

Dynamic Covalent Chemistry as a Facile Route to Unusual Main-Group Thiolate Assemblies and Disulfide Hoops and Cages.

Dynamic Covalent Chemistry (DCC) - combining the robustness of covalent bonds with the self-correcting nature of supramolecular chemistry - facilitates the modular synthesis of complex molecular assemblies in high yields. Although numerous reactions form covalent bonds, only a small set of chemical transformations affect covalent bond formation reversibly under suitable conditions for DCC. Further progress in this area still requires the identification of dynamic motifs and greater insights into their reversibility. We have fruitfully employed DCC of both thiolate coordination to main-group elements and disulfide formation for the facile self-assembly of: (1) metal/metalloid-thiolate assemblies, and (2) purely organic cyclic and caged disulfides, thioethers, and even hydrocarbons, many of which have remained elusive by traditional stepwise synthesis yet form readily through our methods. In this Minireview, we highlight the approaches to prepare these unusual compounds and the factors inducing structural transformations or favoring the formation of certain products over others, given a set of external stimuli or reaction conditions.

Waterproof architectures through subcomponent self-assembly.

Metal-organic containers are readily prepared through self-assembly, but achieving solubility and stability in water remains challenging due to ligand insolubility and the reversible nature of the self-assembly process. Here we have developed conditions for preparing a broad range of architectures that are both soluble and kinetically stable in water through metal(ii)-templated (MII = CoII, NiII, ZnII, CdII) subcomponent self-assembly. Although these structures are composed of hydrophobic and poorly-soluble subcomponents, sulfate counterions render them water-soluble, and they remain intact indefinitely in aqueous solution. Two strategies are presented. Firstly, stability increased with metal-ligand bond strength, maximising when NiII was used as a template. Architectures that disassembled when CoII, ZnII and CdII templates were employed could be directly prepared from NiSO4 in water. Secondly, a higher density of connections between metals and ligands within a structure, considering both ligand topicity and degree of metal chelation, led to increased stability. When tritopic amines were used to build highly chelating ligands around ZnII and CdII templates, cryptate-like water-soluble structures were formed using these labile ions. Our synthetic platform provides a unified understanding of the elements of aqueous stability, allowing predictions of the stability of metal-organic cages that have not yet been prepared.

Transformations in Chemically Responsive Copper-Calixarene Architectures.

Self-assembly of bis-picolyl-appended calix[4]arene (L) with CuI or CuII salts resulted in a collection of multinuclear architectures capable of expressing structural reconfigurations in response to various chemical stimuli: addition of copper salt, solvents, or oxidation. Coordination of L to CuX (X=Br, I) selectively yielded dinuclear macrocycles CuI2 L2 Br2 (1) and CuI2 L2 I2 (3) that were transformed into tetranuclear assemblies CuI4 L2 Br4 (2) and CuI4 L2 I4 (4) upon further addition of CuX. These supramolecules persist as robust and discrete entities in solution that display red emission; notably, 4 exhibits luminescence thermochromism. Assembly of L with CuCl2 produced macrocycle CuII2 L2 Cl4 (5), which crystallised as cage [CuII2 L4 (µ-Cl)]3+ (6) in the presence of MeOH. Two chemical signals-introduction of CuCl2 and addition of CH3 CN-regenerated macrocycle 5. Coordination of L to Cu(OTf) yielded macrocycle CuI2 L2 (OTf)2 (7) that also crystallised as cage 6 upon oxidation in CHCl3 .