Coordination Cages for the Separation and Transportation of Molecular Cargo

The first chapter of this thesis introduces the fundamental concepts governing the design and synthesis of supramolecular complexes. By illustrating the synthesis of several coordination cages reported in the literature, the principles underlying the construction of coordination cages by subcomponent self-assembly are elucidated. Ionic liquids are then proposed as solvents for cage systems; general methods for the preparation and synthesis of these solvents are described. The second chapter explores the use of ionic liquids as solvents for existing coordination cages. Potential methods of characterising these cages in ionic liquids are discussed; cages are demonstrated to be stable and capable of encapsulating guests in these ionic environments; and systems in which cages have good solubility in ionic liquids are designed. Building upon these observations, a triphasic sorting system is presented such that each of three different host-guest complexes are soluble in only one of three immiscible liquid phases. In contrast to the static triphasic system described in the second chapter, the third chapter explores directed phase transfer of coordination cages and their cargos from water, across a phase interface, and into an ionic liquid phase. The host-guest complex can then be recycled from the ionic liquid layer back into water after several additional steps. Furthermore, phase transfer of cationic cages is used to separate a mixture of cationic and anionic host-guest complexes. In the fourth chapter, fully reversible phase transfer of coordination cages is developed. Using anion exchange to modulate the solubility of three different cationic cages, reversible transport between water and ethyl acetate is demonstrated. Sequential phase transfer can also be achieved such that, from a mixture of cubic (+16) and tetrahedral (+8) cages, the cubic cage transfers from water to ethyl acetate before the tetrahedral cage. This process is fully reversible; upon the addition of a hydrophilic anion, the tetrahedral cage returns from ethyl acetate to water before the cubic cage.This work was supported by the European Research Council (259352 and 695009). A.B.G. also acknowledges the Cambridge Trusts for PhD funding

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 (19) F 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 Fe4 L6 2, Fe8 L12 3, and Fe4 L4 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.This work was supported by the European Research Council (259352). We also thank the Cambridge Chemistry NMR service for experimental assistance.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150577

Improving Fatigue Resistance of Dihydropyrene by Encapsulation within a Coordination Cage

Photochromic molecules undergo reversible isomerization upon irradiation with light at different wavelengths, a process that can alter their physical and chemical properties. For instance, dihydropyrene (DHP) is a deep-colored compound that isomerizes to light-brown cyclophanediene (CPD) upon irradiation with visible light. CPD can then isomerize back to DHP upon irradiation with UV light or thermally in the dark. Conversion between DHP and CPD is thought to proceed via a biradical intermediate; bimolecular events involving this unstable intermediate thus result in rapid decomposition and poor cycling performance. Here, we show that the reversible isomerization of DHP can be stabilized upon confinement within a (PdIIL4)-L-6 coordination cage. By protecting this reactive intermediate using the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product obtainable from traditionally low-yielding organic reactions

Coordination Cages Selectively Transport Molecular Cargoes Across Liquid Membranes.

Chemical purifications are critical processes across many industries, requiring 10-15% of humanity's global energy budget. Coordination cages are able to catch and release guest molecules based upon their size and shape, providing a new technological basis for achieving chemical separation. Here, we show that aqueous solutions of FeII4L6 and CoII4L4 cages can be used as liquid membranes. Selective transport of complex hydrocarbons across these membranes enabled the separation of target compounds from mixtures under ambient conditions. The kinetics of cage-mediated cargo transport are governed by guest binding affinity. Using sequential transport across two consecutive membranes, target compounds were isolated from a mixture in a size-selective fashion. The selectivities of both cages thus enabled a two-stage separation process to isolate a single compound from a mixture of physicochemically similar molecules

Directed Phase Transfer of an Fe^II₄L₄ Cage and Encapsulated Cargo

Supramolecular capsules can now be prepared with a wide range of volumes and geometries. Consequently, many of these capsules encapsulate guests selectively by size and shape, an important design feature for separations. To successfully address practical separations problems, however, a guest cannot simply be isolated from its environment; the molecular cargo must be removed to a separate physical space. Here we demonstrate that an Fe^II₄L₄ coordination cage <b>1</b> can transport a cargo spontaneously and quantitatively from water across a phase boundary and into an ionic liquid layer. This process is triggered by an anion exchange from <b>1</b>[SO₄] to <b>1</b>[BF₄]. Upon undergoing a second anion exchange, from <b>1</b>[BF₄] to <b>1</b>[SO₄], the cage, together with its encapsulated guest, can then be manipulated back into a water layer. Furthermore, we demonstrate the selective phase transfer of cationic cages to separate a mixture of two cages and their respective cargoes. We envisage that supramolecular technologies based upon these concepts could ultimately be employed to carry out separations of industrially relevant compounds

Molecular Factors Controlling the Isomerization of Azobenzenes in the Cavity of a Flexible Coordination Cage

Photoswitchable molecules are employed for many applications, from the development of active materials to the design of stimuli-responsive molecular systems and light-powered molecular machines. To fully exploit their potential, we must learn ways to control the mechanism and kinetics of their photoinduced isomerization. One possible strategy involves confinement of photoresponsive switches such as azobenzenes or spiropyrans within crowded molecular environments, which may allow control over their light-induced conversion. However, the molecular factors that influence and control the switching process under realistic conditions and within dynamic molecular regimes often remain difficult to ascertain. As a case study, here we have employed molecular models to probe the isomerization of azobenzene guests within a Pd(II)-based coordination cage host in water. Atomistic molecular dynamics and metadynamics simulations allow us to characterize the flexibility of the cage in the solvent, the (rare) guest encapsulation and release events, and the relative probability/kinetics of light-induced isomerization of azobenzene analogues in these host-guest systems. In this way, we can reconstruct the mechanism of azobenzene switching inside the cage cavity and explore key molecular factors that may control this event. We obtain a molecular-level insight on the effects of crowding and host-guest interactions on azobenzene isomerization. The detailed picture elucidated by this study may enable the rational design of photoswitchable systems whose reactivity can be controlled via host-guest interactions

Guest Encapsulation within Surface-Adsorbed Self-Assembled Cages.

Coordination cages encapsulate a wide variety of guests in the solution state. This ability renders them useful for applications such as catalysis and the sequestration of precious materials. A simple and general method for the immobilization of coordination cages on alumina is reported. Cage loadings are quantified via adsorption isotherms and guest displacement assays demonstrate that the adsorbed cages retain the ability to encapsulate and separate guest and non-guest molecules. Finally, a system of two cages, adsorbed on to different regions of alumina, stabilizes and separates a pair of Diels-Alder reagents. The addition of a single competitive guest results in the controlled release of the reagents, thus triggering their reaction. This method of coordination cage immobilization on solid phases is envisaged to be applicable to the extensive library of reported cages, enabling new applications based upon selective solid-phase molecular encapsulation.UK Engineering and Physical Sciences Research Council (EPSRC EP/P027067/1) , European Research Council (ERC 695009

Heat Engine Drives Transport of an FeII 4 L4 Cage and Cargo.

The directed motion of species against a chemical potential gradient is a fundamental feature of living systems, underpinning processes that range from transport through cell membranes to neurotransmission. The development of artificial active cargo transport could enable new modes of chemical purification and pumping. Here, a heat engine is described that drives chemical cargo between liquid phases to generate a concentration gradient. The heat engine, composed of a functionalized FeII 4 L4 coordination cage, is grafted with oligoethylene glycol imidazolium chains. These chains undergo a conformational change upon heating, causing the cage and its cargo to reversibly transfer between aqueous and organic phases. Furthermore, sectional heating and cooling allow for the cage to traverse multiple phase boundaries, allowing for longer-distance transport than would be possible using a single pair of phases