Novel macrocycles – and old ones doing new tricks

Macrocycles [1] are the workhorses in supramolecular chemistry. Many basic supramolecular concepts have been developed through studying crown ethers, cryptands, podands and spherands in the 1970s and 1980s. For these contributions, Charles Pedersen, Donald J. Cram and Jean-Marie Lehn were awarded the Nobel Prize in Chemistry in 1987. In the 80s and 90s, Jean-Pierre Sauvage and Sir Fraser Stoddart used macrocycles to realize machine-like molecular motion, and they shared the Nobel Prize in Chemistry in 2016 with Ben Feringa. Clearly, macrocycles played a central role for the fundamental science that established supramolecular chemistry as an independent field of chemical research as well as for its applications in contemporary research on functional supramolecules and materials

Supramolecular reactivity in the gas phase: investigating the intrinsic properties of non-covalent complexes

The high vacuum inside a mass spectrometer offers unique conditions to broaden our view on the reactivity of supramolecules. Because dynamic exchange processes between complexes are efficiently suppressed, the intrinsic and intramolecular reactivity of the complexes of interest is observed. Besides this, the significantly higher strength of non-covalent interactions in the absence of competing solvent allows processes to occur that are unable to compete in solution. The present review highlights a series of examples illustrating different aspects of supramolecular gas-phase reactivity ranging from the dissociation and formation of covalent bonds in non-covalent complexes through the reactivity in the restricted inner phase of container molecules and step-by-step mechanistic studies of organocatalytic reaction cycles to cage contraction reactions, processes induced by electron capture, and finally dynamic molecular motion within non-covalent complexes as unravelled by hydrogen–deuterium exchange processes performed in the gas phase

Stimuli-induced folding cascade of a linear oligomeric guest chain programmed through cucurbit[n]uril self-sorting (n = 6, 7, 8)

A six-station linear guest for cucurbit[7]uril and cucurbit[8]uril has been synthesized in order to implement a cascade of transformations driven by external stimuli. The guest chain is sequence-programmed with electron- deficient viologen and electron-rich naphthalene stations linked by either flexible or rigid spacers that affect the chain's folding properties. Together with the orthogonal guest selectivity of the two cucurbiturils, these properties result in self-sorted cucurbituril pseudorotaxane foldamers. Each transformation is controlled by suitable chemical and redox inputs and leads not only to refolding of the guest chain, but also to the liberation of secondary messenger molecules which render the system presented here reminiscent of natural signaling cascades. The steps of the cascade are analyzed by UV/Vis, 1H NMR and electrospray (tandem) mass spectrometry to investigate the different pseudorotaxane structures in detail. With one guest oligomer, three different cucurbiturils, and several different chemical and redox inputs, a chemical system is created which exhibits complex behavior beyond the chemist's paradigm of the pure chemical compound

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

With the rise of artificial molecular machines, control of motion on the nanoscale has become a major contemporary research challenge. Tetrathiafulvalenes (TTFs) are one of the most versatile and widely used molecular redox switches to generate and control molecular motion. TTF can easily be implemented as functional unit into molecular and supramolecular structures and can be reversibly oxidized to a stable radical cation or dication. For over 20 years, TTFs have been key building blocks for the construction of redox-switchable mechanically interlocked molecules (MIMs) and their electrochemical operation has been thoroughly investigated. In this review, we provide an introduction into the field of TTF-based MIMs and their applications. A brief historical overview and a selection of important examples from the past until now are given. Furthermore, we will highlight our latest research on TTF-based rotaxanes

recent strides in new directions

Are they still electrifying? Electrochemically switchable rotaxanes are well known for their ability to efficiently undergo changes of (co-)conformation and properties under redox-control. Thus, these mechanically interlocked assemblies represent an auspicious liaison between the fields of molecular switches and molecular electronics. Since the first reported example of a redox-switchable molecular shuttle in 1994, improved tools of organic and supramolecular synthesis have enabled sophisticated new architectures, which provide precise control over properties and function. This perspective covers recent advances in the area of electrochemically active rotaxanes including novel molecular switches and machines, metal-containing rotaxanes, non-equilibrium systems and potential applications

The Mobility of Homomeric Lasso- and Daisy Chain-Like Rotaxanes in Solution and in the Gas Phase as a means to Study Structure and Switching Behaviour

A precise structural determination of supramolecular architectures is a non-trivial challenge. This daunting task can be made even more difficult when interlocked species are to be analysed having macrocycles covalently equipped with a thread as repeating units, such as molecular lassos and daisy chains. When such functionalized macrocycles are included as scaffolds, different products having analogous NMR spectra as well as dynamic libraries can be obtained. Furthermore, if control over the motion of the parts relative to each other is to be achieved, a full understanding of the machinery's operation mechanism requires detailed insight into the structures involved. This understanding also helps designing improved synthetic molecular machines. Diffusion-ordered NMR spectroscopy and ion-mobility MS techniques are ideal tools to study such compounds in depth. This review covers recent examples on the use of the above-mentioned techniques to characterize these interlocked architectures

The Mobility of Homomeric Lasso- and Daisy Chain-Like Rotaxanes in Solution and in the Gas Phase as a Means to Study Structure and Switching Behaviour

©2023 The Authors. This manuscript version is made available under the CC-BY-NC 4.0 license https://creativecommons.org/licenses/by-nc/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Israel Journal of Chemistry. To access the final edited and published work see https://doi.org/10.1002/ijch.202300022A precise structural determination of supramolecular architectures is a non-trivial challenge. This daunting task can be made even more difficult when interlocked species are to be analysed having macrocycles covalently equipped with a thread as repeating units, such as molecular lassos and daisy chains. When such functionalized macrocycles are included as scaffolds, different products having analogous NMR spectra as well as dynamic libraries can be obtained. Furthermore, if control over the motion of the parts relative to each other is to be achieved, a full understanding of the machinery's operation mechanism requires detailed insight into the structures involved. This understanding also helps designing improved synthetic molecular machines. Diffusion-ordered NMR spectroscopy and ion-mobility MS techniques are ideal tools to study such compounds in depth. This review covers recent examples on the use of the above-mentioned techniques to characterize these interlocked architectures

a versatile strategy for the construction of complex supramolecular architecture

Large protein-sized synthetic supramolecular architecture is rare and certainly has not yet achieved the structural and functional complexity of biomolecules. As multiple, identical copies of a few building blocks are repetitively used, a highly symmetrical architecture results with limitations in function. In marked contrast, functional structures in nature are often assembled with high geometric precision from many different building blocks. They cooperate in a complex way realizing energy conversion, mechanical motion or transport phenomena. Beyond self-assembly, the structurally and functionally complex biomolecular machines rely on self-sorting to correctly position all subunits through orthogonal recognition sites. Mimicking such self-sorting processes is a promising strategy for supramolecular synthesis – resulting in higher structural complexity and promising access to a more sophisticated function. The term “integrative self-sorting” was coined to describe the strategy to form well-defined assemblies with well-controlled subunit positions. The key process is the incorporation of two or more orthogonal binding motifs into at least some of the subunits. Modularity and programmability based on orthogonal yet similar binding motifs generate diversity and complexity. Integrative self-sorting is thus inherently related to systems chemistry. Depending on the individual binding motifs, (multi-)stimuli responsiveness can be achieved. When different recognition events en route to the final assembly occur on significantly different time scales, kinetic pathway selection is observed. In this account, we review the modularity, programmability, and emergent properties of integrative self- sorting, emphasizing its utility and perspective for complex supramolecular architectures

Encapsulation in Charged Droplets Generates Distorted Host-Guest Complexes

The ability of various hydrogen-bonded resorcinarene-based capsules to bind α,ω-alkylbisDABCOnium (DnD) guests of different lengths was investigated in solution and in the gas phase. While no host-guest interactions were detected in solution, encapsulation could be achieved in the charged droplets formed during electrospray ionisation (ESI). This included guests which are far too long in their most stable conformation to fit inside the cavity of the capsules. A combination of three mass spectrometric techniques, collision-induced dissociation, hydrogen/deuterium exchange, and ion-mobility mass spectrometry together with computational modelling allow us to determine the binding mode of the DnD guests inside the cavity of the capsules. Significant distortions of the guest into horseshoe-like arrangements are required to optimise cation-π interactions with the host which also adopt distorted geometries with partially open hydrogen-bonding seams when binding longer guests. Such quasi “spring-loaded” capsules can form in the charged droplets during the ESI process as there is no competition between guest encapsulation and ion pair formation with the counterions that preclude encapsulation in solution. The encapsulation complexes are sufficiently stable in the gas phase – even when strained – because non-covalent interactions significantly strengthen in the absence of solvent

Lower critical solution temperature (LCST) phase behaviour of an ionic liquid and its control by supramolecular host–guest interactions

Lower critical solution temperature (LCST) phase behaviour of an imidazolium- based ionic liquid is reported, which can be controlled by concentration, the choice of cation, anion and solvent, and by supramolecular host–guest complex formation. Molecular dynamics simulations provide insight into the molecular basis of this LCST phenomenon. This thermo-responsive system has potential applications in cloud point extraction processes