Water-soluble macrocycles are useful molecular hosts for drug delivery, stimuli-responsive materials, water purification and many other applications. However, controlling the host-guest chemistry of macrocycles such as cyclodextrins under physiologically relevant conditions is a major challenge. Here we demonstrate the use of dynamic pericyclic chemistry to derivatise guests for cyclodextrins under mild conditions, thereby turning off molecular recognition. We show that the Diels-Alder [4 + 2] cycloaddition reaction between anthracene derivatives and activated alkenes proceed rapidly, selectively and reversibly in water under ambient conditions. This reaction can be used to modulate binding of both native and modified β-cyclodextrins to the anthracene. By appropriate choice of conditions, the resulting chemical reaction network could also operate under non-equilibrium steady state conditions. Finally, alkene scavengers could induce the retro-Diels Alder reactions, allowing the use of the pericyclic reaction system as a molecular switch. (Figure presented.)

Luminescent emitters based on lanthanide ions are of ubiquitous importance in the biological sciences, but typically need sensitization from a covalently attached adjacent chromophore – an “antenna” – to have suitable emission intensities. Here we show that the mechanical bond can be used to connect the antenna to the emitter, providing dynamic features and stimuli‐responsiveness to the resulting assemblies. We outline a strategy to synthesize [2]rotaxanes capped with strong chelating groups, and establish that post‐functionalization of the interlocked scaffold by lanthanide ion insertion is modular, high‐yielding and straightforward. Photophysical studies revealed effective antenna‐emitter energy transfer within the [2]rotaxane, and the sensitization mechanism as well as ring‐thread dynamics were studied with spectroscopic and computational methods. The rotaxane was shown to have high selectivity toward Cu(II) ions, acting as an efficient turn‐off sensor. This study validates the mechanical bond as a conjugation method between antennas and emitters, yielding otherwise hard‐to‐access and beneficial features to the resulting molecular systems.

Here, we highlight 35 global researchers approximately under the age of 35. This third annual cohort was self-generated by initial seed invitations sent by the editorial team, with each contributor suggesting two more in a nominally supervised self-selecting pyramid-like scheme. The final collection reflects both the diversity and excitement across the field of materials science.

Dynamic covalent boronic ester bonds can pre-organise diol-containing threads and V-shaped boronic acid ligands towards mechanical interlocking. After interlocking, the pre-rotaxane could be modified to create many unique [2]rotaxanes architectures.

We report on the synthesis of [2]rotaxanes from vicinal diols through dynamic covalent boronic ester templates, as well as the use of the boronic ester for rotaxane post-functionalisation. A boronic acid pincer ligand with two alkene-appended arms was condensed with a linear diol-containing thread, and ring-closing metathesis established a pre-rotaxane architecture along with a non-entangled isomer. Advanced NMR spectroscopy and mass spectrometry unambiguously assigned the isomers and revealed that the pre-rotaxane was in equilibrium with its hydrolyzed free [2]rotaxane form. The boronic ester handle in the pre-rotaxane could be synthetically addressed in a multitude of ways to obtain different endo -functionalised [2]rotaxanes, including with direct oxidation reactions, protodeboronation, functional group interconversions and Pd-catalysed cross-couplings.

Mechanically interlocked molecules have found extensive applications in areas all across the physical sciences, from materials to catalysis and sensing. However, introducing mechanical bonds and entanglements at the molecular level is still a significant challenge due to the inherent restriction in entropy needed to preorganize strands before interlocking. Over the last decade, dynamic covalent chemistry has emerged as one of the most efficient methods of forming rotaxanes, catenanes and molecular knots. By using reversible bonds such as imines, disulfides and boronate esters, one can use the inherent error-correction in these linkages to form interlocked architectures with high fidelity and often in excellent yields. This review reports on recent advances in the use of dynamic covalent chemistry to make mechanically interlocked molecules, systematically surveying clipping, capping and templating approaches with dynamic bonds. Furthermore, it is also discussed how dynamic bonds can be used to control motion, co-conformational expression and catalytic activity in mechanically interlocked molecular machinery.

Interlocking macrocyclic carbon nanomaterials is an exciting way to tune their molecular properties, but all-conjugated catenanes and rotaxanes are extremely challenging to make. Now, fully π-conjugated [2]- and [3]catenanes as well as a [3]rotaxane have been prepared through an ‘active metal template’ approach.

The field of mechanically interlocked molecules (MIMs) has advanced rapidly in recent years, with much work focused on their use in materials, sensing, and catalysis. However, the use of MIMs in biology and biomedicine has been limited, despite the identifica-tion of naturally occurring MIMs in DNA and proteins and the poten-tial advantages of the mechanical bond in fields such as nanomedi-cine and tissue engineering. Difficulties in the synthesis of MIMs, along with their limited solubility and stability in biological media, have until recently impeded their wider application in biology. Contemporary advances have, however, enabled a broader integra-tion of the mechanical bond in biology; the mechanical interlocking endows these systems with unique functional advantages. Herein, we summarize recent advances in the application of small-molecule, biologically derived, and polymeric MIMs in biology, highlighting synergies ripe for future exploration.

Creating artificial molecular machines that perform well-defined unidirectional movement in response to stimuli is a challenging task. In this issue of Chem, Crespi, Feringa, and co-workers report a new bis(benzoxazole) ligand-based molecular motor that enables a high degree of external control over motor function through complexation with metal ions.

Understanding the emergence of function in complex reaction networks is a primary goal of systems chemistry and origin-of-life studies. Especially challenging is to create systems that simultaneously exhibit several emergent functions that can be independently tuned. In this work, a multifunctional complex reaction network of nucleophilic small molecule catalysts for the Morita-Baylis-Hillman (MBH) reaction is demonstrated. The dynamic system exhibited triggered self-resolution, preferentially amplifying a specific catalyst/product set out of a many potential alternatives. By utilizing selective reversibility of the products of the reaction set, systemic thermodynamically driven error-correction could also be introduced. To achieve this, a dynamic covalent MBH reaction based on adducts with internal H-transfer capabilities was developed. By careful tuning of the substituents, rate accelerations of retro-MBH reactions of up to four orders of magnitude could be obtained. This study thus demonstrates how efficient self-sorting of catalytic systems can be achieved through an interplay of several complex emergent functionalities.

The reversibility of imine bonds has been exploited to great effect in the field of dynamic covalent chemistry, with applications such as preparation of functional systems, dynamic materials, molecular machines, and covalent organic frameworks. However, acid catalysis is commonly needed for efficient equilibration of imine mixtures. Herein, it is demonstrated that hydrogen bond donors such as thioureas and squaramides can catalyze the equilibration of dynamic imine systems under unprecedentedly mild conditions. Catalysis occurs in a range of solvents and in the presence of many sensitive additives, showing moderate to good rate accelerations for both imine metathesis and transimination with amines, hydrazines, and hydroxylamines. Furthermore, the catalyst proved simple to immobilize, introducing both reusability and extended control of the equilibration process.