Jonathan R. Nitschke

White Phosphorus Is Air-Stable Within a Self-Assembled Tetrahedral Capsule

Molecular Fire Quencher Cage-shaped molecular assemblies can regulate the reactivity of smaller molecules trapped within them. Mal et al. (p. 1697) extend this approach to enable the protection of elemental white phosphorus (P4), a substance that rapidly ignites on contact with oxygen. The tetrahedral cages self-assemble in aqueous solution through coordination of six ligands to four iron ions, and efficiently capture phosphorus from a suspension. The water-soluble host-guest constructs were stable in air for at least 4 months, but released intact P4 rapidly on displacement by added benzene. A molecular cage keeps phosphorus from igniting in air, yet releases it easily for reactions when benzene is added. The air-sensitive nature of white phosphorus underlies its destructive effect as a munition: Tetrahedral P4 molecules readily react with atmospheric dioxygen, leading this form of the element to spontaneously combust upon exposure to air. Here, we show that hydrophobic P4 molecules are rendered air-stable and water-soluble within the hydrophobic hollows of self-assembled tetrahedral container molecules, which form in water from simple organic subcomponents and iron(II) ions. This stabilization is not achieved through hermetic exclusion of O2 but rather by constriction of individual P4 molecules; the addition of oxygen atoms to P4 would result in the formation of oxidized species too large for their containers. The phosphorus can be released in controlled fashion without disrupting the cage by adding the competing guest benzene.

Stimuli-Responsive Metal-Ligand Assemblies.

The Engineering and Physical Sciences Research Council and the European Research Council are acknowledged for financial support.

A Self‐Assembled M8L6 Cubic Cage that Selectively Encapsulates Large Aromatic Guests

Biological encapsulants such as ferritin, lumazine synthase, and viral capsids achieve their selective separation and sequestration of substrates by providing: 1) a guest microenvironment isolated from the surroundings, 2) favorable interactions complementing a size and shape match with the encapsulated guests, and 3) sufficient flexibility to allow guests to be incorporated and released. These biological hosts self-assemble from multiple copies of identical protein subunits, the symmetries and connection properties of which dictate the hollow polyhedral structures of the encapsulant. In order to create abiological molecular systems that are capable of expressing functions of similar complexity to biological systems and to explore new applications of synthetic hosts, there is a need to create synthetic capsules capable of tightly and selectively binding large substrates. Taking inspiration from natural systems and from other previously reported metal–organic capsules, we report the design and synthesis of a series of metallo-supramolecular cage molecules capable of selectively encapsulating large aromatic guests. The necessary features to achieve this function are: 1) small pore sizes to isolate guests from the environment, 2) large cavity sizes to ensure sufficient volume for the guests of interest, 3) enough flexibility and lability to allow guests to enter and exit the host, and 4) regions of the cage walls rich in p-electron density to provide favorable interactions with targeted guests. The selective encapsulation of large aromatic molecules is an attractive goal since their physicochemical properties are similar, which can render their separation difficult. The higher fullerenes represent particularly attractive targets because their potential applications remain difficult to explore because of the challenges associated with their separation, despite recent advances. Employing principles of geometric analysis, we determined that combination of the C4-symmetric tetrakis-bidentate ligand shown in Figure 1 with the C3-symmetric iron(II) tris(pyridylimine) center would result in the formation of an O-symmetric cubic structure of general formula M8L6, in which the corners of the cube are defined by the metal centers and the faces by the ligands (Figure 1). This cage represents the first example of a new class of closed-face metallosupramolecular cubic hosts to be synthesized. In order to provide favorable binding sites for our target guests we incorporated porphyrin moieties, which have previously been demonstrated to interact with large aromatic molecules, into our design. This design also provides for small pore sizes and the potential to create new chemical functionality through the introduction of different metal ions into the centers of the N4 macrocycle and by substituting these metals axial ligands. We chose to employ labile iron(II) centers with pyridylimine ligands as chelating agents to allow for the formation of the ligand in situ through the subcomponent self-assembly approach. The reaction between tetrakis(4-aminophenyl)porphyrin (H2-tapp), 2-formylpyridine, and iron(II) trifluoromethanesulfonate (triflate, OTf ) in DMF produced cage [H21]·16OTf (Figure 1) as the uniquely observed product, as verified by NMR spectroscopy (Figure 3b), electrospray mass spectrometry (ESI-MS), and elemental analysis. Substitution of nickel(II) tetrakis(4-aminophenyl)porphyrin (Ni-tapp) or zinc(II) tetrakis(4-aminophenyl)porphyrin (Zn-tapp) for H2tapp under identical conditions yielded the nickel-containing (Ni-1) and zinc-containing (Zn-1) congeners of H2-1 (Figures S2a and S3a in the Supporting Information), respectively, suggesting the formation of such capsules to be a general feature of tetrakis(4-aminophenyl) porphyrins (Figure 1). Vapor diffusion of diethyl ether into a DMF/acetonitrile solution of Ni-1 resulted in the isolation of block-shaped dark purple crystals. Single-crystal X-ray diffraction revealed a solid-state structure (Figure 2) consistent with the O-symmetric NMR spectra recorded in solution. Each face of Ni-1 is covered by one porphyrin ligand and each corner is defined by a six-coordinate low-spin Fe ion. All of the Fe centers within each cage adopt the sameL or D configuration; both enantiomers of Ni-1 are present in the crystal lattice. The Ni–Ni distance between opposite faces is 15 , and the internal cavity volume is 1340 3 (Figure S2e). [*] W. Meng, Dr. B. Breiner, Prof. J. D. Thoburn, Dr. J. K. Clegg, Dr. J. R. Nitschke University of Cambridge, Department of Chemistry Lensfield Road, Cambridge, CB2 1EW (UK) E-mail: jrn34@cam.ac.uk Homepage: http://www-jrn.ch.cam.ac.uk/

Stereochemistry in Subcomponent Self-Assembly

CONSPECTUS: As Pasteur noted more than 150 years ago, asymmetry exists in matter at all organization levels. Biopolymers such as proteins or DNA adopt one-handed conformations, as a result of the chirality of their constituent building blocks. Even at the level of elementary particles, asymmetry exists due to parity violation in the weak nuclear force. While the origin of homochirality in living systems remains obscure, as does the possibility of its connection with broken symmetries at larger or smaller length scales, its centrality to biomolecular structure is clear: the single-handed forms of bio(macro)molecules interlock in ways that depend upon their handednesses. Dynamic artificial systems, such as helical polymers and other supramolecular structures, have provided a means to study the mechanisms of transmission and amplification of stereochemical information, which are key processes to understand in the context of the origins and functions of biological homochirality. Control over stereochemical information transfer in self-assembled systems will also be crucial for the development of new applications in chiral recognition and separation, asymmetric catalysis, and molecular devices. In this Account, we explore different aspects of stereochemistry encountered during the use of subcomponent self-assembly, whereby complex structures are prepared through the simultaneous formation of dynamic coordinative (N → metal) and covalent (N═C) bonds. This technique provides a useful method to study stereochemical information transfer processes within metal-organic assemblies, which may contain different combinations of fixed (carbon) and labile (metal) stereocenters. We start by discussing how simple subcomponents with fixed stereogenic centers can be incorporated in the organic ligands of mononuclear coordination complexes and communicate stereochemical information to the metal center, resulting in diastereomeric enrichment. Enantiopure subcomponents were then incorporated in self-assembly reactions to control the stereochemistry of increasingly complex architectures. This strategy has also allowed exploration of the degree to which stereochemical information is propagated through tetrahedral frameworks cooperatively, leading to the observation of stereochemical coupling across more than 2 nm between metal stereocenters and the enantioselective synthesis of a face-capped tetrahedron containing no carbon stereocenters via a stereochemical memory effect. Several studies on the communication of stereochemistry between the configurationally flexible metal centers in tetrahedral metal-organic cages have shed light on the factors governing this process, allowing the synthesis of an asymmetric cage, obtained in racemic form, in which all symmetry elements have been broken. Finally, we discuss how stereochemical diversity leads to structural complexity in the structures prepared through subcomponent self-assembly. Initial use of octahedral metal templates with facial stereochemistry in subcomponent self-assembly, which predictably gave rise to structures of tetrahedral symmetry, was extended to meridional metal centers. These lower-symmetry linkages have allowed the assembly of a series of increasingly intricate 3D architectures of varying functionality. The knowledge gained from investigating different aspects of the stereochemistry of metal-templated assemblies thus not only leads to new means of structural control but also opens pathways toward functions such as stereoselective guest binding and transformation.

Anion-induced reconstitution of a self-assembling system to express a chloride-binding Co10L15 pentagonal prism

Biochemical systems are adaptable, capable of reconstitution at all levels to achieve the functions associated with life. Synthetic chemical systems are more limited in their ability to reorganize to achieve new functions; they can reconfigure to bind an added substrate (template effect) or one binding event may modulate a receptors affinity for a second substrate (allosteric effect). Here we describe a synthetic chemical system that is capable of structural reconstitution on receipt of one anionic signal (perchlorate) to create a tight binding pocket for another anion (chloride). The complex, barrel-like structure of the chloride receptor is templated by five perchlorate anions. This second-order templation phenomenon allows chemical networks to be envisaged that express more complex responses to chemical signals than is currently feasible.

Systems chemistry: Molecular networks come of age

The advent of sophisticated analytical tools enables the collective behaviour of networks of interacting molecules to be studied. The emerging field of systems chemistry promises to allow such networks to be designed to perform complex functions, and might even shed light on the origins of life.

Integrative Self‐Sorting Synthesis of a Fe8Pt6L24 Cubic Cage

The many different chemical processes associated with life run in parallel within the cytoplasm of a cell. These processes are not spatially separated by membranes, yet they do not interfere with each other. The biomolecular agents of these processes can be said to undergo self-sorting, which is defined as “the high-fidelity recognition of self from nonself”, into the locally organized systems that achieve individual functions. The goal of creating synthetic self-sorting systems is thus inspired in part by the prospect of synthesizing functional supramolecular systems that carry out different processes together in solution. Self-assembled metal–organic capsules have been shown to be useful for a variety of applications, including guest binding and separation, cavity-controlled catalysis, generation of unusual reaction products, and stabilization of reactive intermediates. New strategies have been explored to prepare more complex, metal–organic capsules so as to achieve new functions. The potential of self-sorting has only recently been acknowledged by researchers as a method for preparing such capsules. One strategy pursued by researchers to create progressively more-complex metal–organic architectures has been the preparation of heteroleptic species. This method relies on the combination of at least two types of homotopic ligands and a single metal ion for the construction of a metal–organic complex. An alternative method to create complexity, employed herein, entails the use of a single heterotopic ligand and more than one metal ion, wherein the fidelity of the self-assembly relies on integrative self-sorting. Our construction method relies on two different metal ions and coordination environments: in addition to the tris(pyridylimine)iron(II) moiety, widely employed in the subcomponent self-assembly of complex structures, we have introduced a second coordination motif, the tetrakis(pyridine)platinum(II) moiety. To this end, ditopic ligand 1 (Scheme 1), was selected as a ligand that can coordinate to both Fe (as a tris(pyridylimine) complex) and Pt ions (through its terminal pyridine group). Based on the fourfold symmetry of the tetrakis(pyridine)platinum(II) moiety and the threefold symmetry of the tris(pyridylimine)iron(II) moiety, we envisioned the possibility of preparing a heterometallic cubic capsule: after synthesis of the square-planar Pt complex 2, this intermediate could be incorporated into heterometallic cube 3 by formation of Fe-stabilized pyridylimine bonds (Scheme 1, right). Self-sorting could be validated within such a system by starting with the free subcomponents and metal ions, and allowing each to find its proper place within the final product structure (Scheme 1, left). For this selfassembly process to work, the two different kinds of sphybridized nitrogen donors must bind to the correct metal ions, without scrambling. Herein we employ integrative self-sorting in the synthesis of the heterometallic Fe8Pt6L24 cube 3 (Scheme 1). A one-pot synthesis of cube 3 from four different components, in which a total of 62 building blocks are brought together, was found to be possible, thus demonstrating both the potential of selfScheme 1. The two-step synthesis of cube 3 via the square-planar Pt intermediate 2 and the one-pot synthesis of 3 starting from free subcomponents and metal ions. For clarity, the chemical structure of only one of the six faces of the cube is shown.

Selective anion binding by a “Chameleon” capsule with a dynamically reconfigurable exterior

A new class of tetrahedral metal–organic capsules that can incorporate up to twelve different externally-directed amine residues is reported, allowing for very large dynamic libraries to be formed from mixtures of amines. Selectivity is observed both externally—more electron-rich amines are incorporated in favour of electron-poor amines—and internally—PF6− is bound in preference to CF3SO3− or BF4−.

Subcomponent self-assembly and guest-binding properties of face-capped Fe4L48+ capsules

A general method for preparing Fe(4)L(4) face-capped tetrahedral cages through subcomponent self-assembly was developed and has been demonstrated using four different C(3)-symmetric triamines, 2-formylpyridine, and iron(II). Three of the triamines were shown also to form Fe(2)L(3) helicates when the appropriate stoichiometry of subcomponents was used. Two of the cages were observed to have nearly identical Fe-Fe distances in the solid state, which enabled their ligands to be coincorporated into a collection of mixed cages. Only one of the cages combined a sufficiently large cavity with the sufficiently small pores required for guest binding, taking up a wide variety of guest species in size- and shape-selective fashion.

Self-organization by selection: Generation of a metallosupramolecular grid architecture by selection of components in a dynamic library of ligands

Self-organization by selection is implemented in the generation of a tetranuclear [2 × 2] grid-type metallosupramolecular architecture from its components. It occurs through a two-level self-assembly involving two dynamic processes: reversible covalent bound connection and reversible metal ion coordination. Thus, mixing the aminophenol 3, the dialdehyde 4, and zinc acetate generates the grid complex 1a(Zn) via the assembly of the ligand 2a by imine formation and of the grid by zinc(II) binding. When the same process is conducted in a solution containing a mixture of different aminophenol and carbonyl components, the generation of the grid 1a(Zn) drives the selection of the correct components in a virtual dynamic library of ligands, displaying an amplification factor of >100 and a selectivity of >99%. Component exchange as well as reversible protonic modulation of the assembly/disassembly process display the dynamic character of the system and its ability to respond/adapt to changes in environmental conditions. The processes described demonstrate the implementation of a two-level self-organization by selection operating on the dynamic diversity generated by a set of reversibly connected components and driven by the formation of a specific product in a “self-design” fashion.