Matthew J. Langton

Halogen bonding in water results in enhanced anion recognition in acyclic and rotaxane hosts

Halogen bonding (XB), the attractive interaction between an electron-deficient halogen atom and a Lewis base, has undergone a dramatic development as an intermolecular force analogous to hydrogen bonding (HB). However, its utilization in the solution phase remains underdeveloped. Furthermore, the design of receptors capable of strong and selective recognition of anions in water remains a significant challenge. Here we demonstrate the superiority of halogen bonding over hydrogen bonding for strong anion binding in water, to the extent that halide recognition by a simple acyclic mono-charged receptor is achievable. Quantification of iodide binding by rotaxane hosts reveals the strong binding by the XB-rotaxane is driven exclusively by favourable enthalpic contributions arising from the halogen-bonding interactions, whereas weaker association with the HB-rotaxanes is entropically driven. These observations demonstrate the unique nature of halogen bonding in water as a strong alternative interaction to the ubiquitous hydrogen bonding in molecular recognition and assembly.

Rotaxane and catenane host structures for sensing charged guest species.

CONSPECTUS: The promise of mechanically interlocked architectures, such as rotaxanes and catenanes, as prototypical molecular switches and shuttles for nanotechnological applications, has stimulated an ever increasing interest in their synthesis and function. The elaborate host cavities of interlocked structures, however, can also offer a novel approach toward molecular recognition: this Account describes the use of rotaxane and catenane host systems for binding charged guest species, and for providing sensing capability through an integrated optical or electrochemical reporter group. Particular attention is drawn to the exploitation of the unusual dynamic properties of interlocked molecules, such as guest-induced shuttling or conformational switching, as a sophisticated means of achieving a selective and functional sensor response. We initially survey interlocked host systems capable of sensing cationic guests, before focusing on our accomplishments in synthesizing rotaxanes and catenanes designed for the more challenging task of selective anion sensing. In our group, we have developed the use of discrete anionic templation to prepare mechanically interlocked structures for anion recognition applications. Removal of the anion template reveals an interlocked host system, possessing a unique three-dimensional geometrically restrained binding cavity formed between the interlocked components, which exhibits impressive selectivity toward complementary anionic guest species. By incorporating reporter groups within such systems, we have developed both electrochemical and optical anion sensors which can achieve highly selective sensing of anionic guests. Transition metals, lanthanides, and organic fluorophores integrated within the mechanically bonded structural framework of the receptor are perturbed by the binding of the guest, with a concomitant change in the emission profile. We have also exploited the unique dynamics of interlocked hosts by demonstrating that an anion-induced conformational change can be used as a means of signal transduction. Electrochemical sensing has been realized by integration of the redox-active ferrocene functionality within a range of rotaxane and catenanes; binding of an anion perturbs the metallocene, leading to a cathodic shift in the ferrocene/ferrocenium redox couple. In order to obtain practical sensors for target charged guest species, confinement of receptors at a surface is necessary in order to develop robust, reuseable devices. Surface confinement also offers advantages over solution based receptors, including amplification of signal, enhanced guest binding thermodynamics and the negation of solubility problems. We have fabricated anion-templated rotaxanes and catenanes on gold electrode surfaces and demonstrated that the resulting mechanically bonded self-assembled monolayers are electrochemically responsive to the binding of anions, a crucial first step toward the advancement of sophisticated, highly selective, anion sensory devices. Rotaxane and catenane host molecules may be engineered to offer a superior level of molecular recognition, and the incorporation of optical or electrochemical reporter groups within these interlocked frameworks can allow for guest sensing. Advances in synthetic templation strategies has facilitated the synthesis of interlocked architectures and widened their interest as prototype molecular machines. However, their unique host-guest properties are only now beginning to be exploited as a sophisticated approach to chemical sensing. The development of functional host-guest sensory systems such as these is of great interest to the interdisciplinary field of supramolecular chemistry.

Anion Recognition in Water: Recent Advances from a Supramolecular and Macromolecular Perspective.

Abstract The recognition of anions in water remains a key challenge in modern supramolecular chemistry, and is essential if proposed applications in biological, medical, and environmental arenas that typically require aqueous conditions are to be achieved. However, synthetic anion receptors that operate in water have, in general, been the exception rather than the norm to date. Nevertheless, a significant step change towards routinely conducting anion recognition in water has been achieved in the past few years, and this Review highlights these approaches, with particular focus on controlling and using the hydrophobic effect, as well as more exotic interactions such as C−H hydrogen bonding and halogen bonding. We also look beyond the field of small‐molecule recognition into the macromolecular domain, covering recent advances in anion recognition based on biomolecules, polymers, and nanoparticles.

Template-directed synthesis of π-conjugated porphyrin [2]rotaxanes and a [4]catenane based on a six-porphyrin nanoring

[2]Rotaxanes consisting of butadiyne-linked porphyrin dimers threaded through a phenanthroline-containing macrocycle, can be synthesised by an active-metal template directed copper-mediated Glaser coupling, in yields of up to 61%, without requiring a large excess of the macrocycle. The crystal structure of one of these rotaxanes confirms that the macrocycle is clasped around the centre of the porphyrin dimer. A radial hexa-pyridyl template was used to convert the alkyne-terminated [2]rotaxane into a [4]catenane cyclic porphyrin hexamer in 62% yield, viapalladium-catalysed Glaser coupling. The related [7]catenane porphyrin dodecamer complex was also isolated as a by-product of this cyclisation, in 6% yield. These results illustrate the scope of template-directed synthesis for creating complex interlocked structures directly from simple starting materials.

Iodide Recognition and Sensing in Water by a Halogen-Bonding Ruthenium(II)-Based Rotaxane

Abstract The synthesis and anion‐recognition properties of the first halogen‐bonding rotaxane host to sense anions in water is described. The rotaxane features a halogen‐bonding axle component, which is stoppered with water‐solubilizing permethylated β‐cyclodextrin motifs, and a luminescent tris(bipyridine)ruthenium(II)‐based macrocycle component. 1H NMR anion‐binding titrations in D2O reveal the halogen‐bonding rotaxane to bind iodide with high affinity and with selectively over the smaller halide anions and sulfate. The binding affinity trend was explained through molecular dynamics simulations and free‐energy calculations. Photo‐physical investigations demonstrate the ability of the interlocked halogen‐bonding host to sense iodide in water, through enhancement of the macrocycle component’s RuII metal–ligand charge transfer (MLCT) emission.

Nitrite-Templated Synthesis of Lanthanide-Containing [2]Rotaxanes for Anion Sensing

The first anion-templated synthesis of a lanthanide-containing interlocked molecule is demonstrated by utilizing a nitrite anion to template initial pseudorotaxane formation. Subsequent stoppering of the interpenetrated assembly allows for the preparation of a lanthanide-functionalized [2]rotaxane in high yield. Following removal of the nitrite anion template, the europium [2]rotaxane host is demonstrated to recognize and sense fluoride selectively.

Sulfate‐Selective Binding and Sensing of a Fluorescent [3]Rotaxane Host System

The chloride-templated synthesis of a novel [3]rotaxane, capable of binding anionic guests, and incorporating a naphthalene group for fluorescence sensing is reported. Extensive (1)H NMR titration studies were used to probe the anion binding selectivity of the system. The rotaxane selectively recognises sulfate, undergoing an induced conformational change upon sulfate binding to form a 1:1 stoichiometric sandwich-type complex, concomitant with significant quenching of the fluorescence. Binding of mono-anionic guests results in the formation of a 2:1 stoichiometric guest-host complex, and a modest enhancement of the emission. Addition of an excess of sulfate in non-competitive solvent also results in a 2:1 emissive complex.

Lanthanide cation-templated synthesis of rotaxanes.

The first lanthanide cation-templated synthesis of an interlocked structure is demonstrated through an interpenetrated assembly between a pyridine N-oxide threading component coordinating to a lanthanide cation complexed within a macrocycle. Stoppering of the pseudo-rotaxane assembly allows for preparation of the [2]rotaxane.

Active‐Metal Template Synthesis of a Halogen‐Bonding Rotaxane for Anion Recognition

Abstract The synthesis of an all‐halogen‐bonding rotaxane for anion recognition is achieved by using active‐metal templation. A flexible bis‐iodotriazole‐containing macrocycle is exploited for the metal‐directed rotaxane synthesis. Endotopic binding of a CuI template facilitates an active‐metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper‐template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen‐bond donors into the rotaxane’s interlocked binding cavity to facilitate anion recognition.

Controlled membrane translocation provides a mechanism for signal transduction and amplification

Transmission and amplification of chemical signals across lipid bilayer membranes is of profound significance in many biological processes, from the development of multicellular organisms to information processing in the nervous system. In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, and signal transduction is often associated with an amplified signalling cascade. The ability to reproduce such processes in artificial systems has potential applications in sensing, controlled drug delivery and communication between compartments in tissue-like constructs of synthetic vesicles. Here we describe a mechanism for transmitting a chemical signal across a membrane based on the controlled translocation of a synthetic molecular transducer from one side of a lipid bilayer membrane to the other. The controlled molecular motion has been coupled to the activation of a catalyst on the inside of a vesicle, which leads to a signal-amplification process analogous to the biological counterpart.