Mechanical Bond Chemistry
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Mechanical bond refers to physical entanglement in space that links molecular entities together. As a bond type of fundamentally different nature than covalent bond, mechanical bond gives rise to molecular properties that are completely different and unavailable in conventional covalent molecules. For example, because motions of the interlocked components are not covalently restricted, mechanically interlocked molecules could undergo large-amplitude motions as a result of stimulus application - such property is the basis of using rotaxanes and catenanes as molecular machine and switches. New stereochemistry can also arise due to the mechanical bond and/or the topology of the interlocked molecules.
To explore the new opportunities from mechanical bonding, we develop new synthetic strategies for the efficient and controllable synthesis of mechanically bonded molecules and study the new and unique properties as a result of the mechanical bond. We are particularly interested in catenane (e.g., Chem. Sci. 2022, 13, 3315 and Inorg. Chem. 2018, 57, 3415) that is consisted of interlocked macrocycles and are exploring these mechanically interlocked molecules for applications in recognition, sensing, catalysis, and molecular materials.
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New Synthetic Strategies to High-Order Catenane
Catenane is one representative class of mechanically interlocked molecules consisted of interlocked macrocycles. Due to the non-trivial topology, catenane synthesis has long been very challenging. Most of the reported catenanes are of relatively simple structures and contain few numbers of interlocked rings. Efficient synthesis of high-order catenanes with more than three interlocked macrocycles remains difficult but essential for expanding the chemistry of mechanical bond.
By careful building block design to maximize the efficiency of the preorganization and ring-closing steps in a templated catenane synthesis, we have been able to synthesize high-order [5]-, [6]-, [7]- and [8]catenanes in good yields (>90%). In particular, we have been using the cucurbit[6]uril-mediated azide-alkyne cycloaddition to couple the preorganization step with macrocycle formation, so that the mechanical interlocking proceeds with very high efficiency (e.g., Chem. Sci. 2016, 7, 2787). Isolation and purification of these [n]catenanes are straightforward as a result of the efficient synthesis.
By using strategically designed building blocks, we have also realized the first example of a pair of catenane isomers in which the macrocycles are interlocked in different sequences (Angew. Chem. Int. Ed. 2019, 58, 17375). Details spectroscopic studies on the [5]catenanes showed that dynamics of the interlocked cyclodextrin not only is dependent on the sequence of the peripheral macrocycles, but also on the basicity of the environment as a result of the coupled motions to that of the interlocked CB[6], although cyclodextrin itself is pH insensitive.
Dynamics of High-Order Catenanes
The ability of the interlocked components to undergo large-amplitude motions is one most characteristic property of mechanically interlocked molecules, and hence increasing the complexity of catenane structures for more diverse dynamics and stimuli-triggered motions is of fundamental importance in expanding the forefront of mechanical bond chemistry.
By using our developed strategies to obtain [n]catenane composed of interlocked macrocycles of different constitutions and stimuli-responsiveness, we are able to study dynamics in complex [n]catenane and investigate how the motions of different macrocycles are influencing each other. In addition to the above [5]catenane isomers, we have also prepared a pair of [4]catenane isomer in which the two biphenyl stations and CB[6] "speedbumps" are arranged in different sequence with different cyclodextrin dynamics (Org. Chem. Front. 2021, 8, 2182).
More recently, we have also prepared a branched [8]catenane (one of the largest discreet [n]catenanes isolated to date) in which its dynamics at the peripheral, middle and core positions can be respectively controlled by three orthogonal stimuli (i.e., ionic strength, pH and metal ions) and result in dynamics control in three different amplitudes (Angew. Chem. Int. Ed. 2022, 61, e202110200).
Catenane Ligands in Coordination Chemistry and Catalysis
While coordination ligands are central to the properties and reactivity of metal complexes, ligand mechanical interlocking is almost a virgin territory in terms of ligand design for exploring new coordination chemistry, especially in the field of transition metal catalysis. For example, although the Cu(I)-bis(phenanthroline) coordination is one of the most classical templates in MIMs synthesis and that many copper complexes supported by catenane or rotaxane ligands are known, catalytic properties of these copper complexes are largely unknown.
In 2020, we showed for the first time that a catenane-coordinated Cu(I) complex is active towards catalyzing the cross C-O coupling of phenol and bromodicarbonyl substrates (Chem. Sci. 2020, 11, 13008). Comparing with the control complex of the same primary Cu(I) coordination but non-interlocked ligands, our experiments showed that the mechanical bond limits ligand exchange, so that the Cu(I) active site in the catenane catalyst is more robust with a longer lifetime, enhanced activity and more well-defined reaction profile, suggesting new catalytic activity could be resulted only from ligand interlocking.
More recently, as a collaboration with the research group of Dr. Edmund Tse (HKU), we demonstrate that the phenanthroline-derived copper catenane complexes are also active catalyst towards the electrochemical oxygen reduction reaction with activity and selectivity rivaling those state-of-the-art molecular copper catalysts with a sophisticated design and ligand sets (J. Am. Chem. Soc. DOI: 10.1021/jacs.2c10988). We found that the activity and selectivity of the copper catenane complexes are related to the size of the interlocked macrocycles, which we propose to be an important parameter dictating the ease of ligand rearrangement that is implicated in substrate acceptance, chemical transformation, electron transfer and product elimination during the catalysis. Also, the mechanical interlocking could help orient the dioxygen substrate and steer the reduction to the 4-electron pathway to give water over hydrogen peroxide.
Catenane for Recognition, Sensing and other Applications
We are also exploring other aspects of catenane chemistry, for example, the development of catenane-based molecular switches that are responsive towards various external stimuli (Chem. Commun. 2021, 57, 2931), the use of the protected binding pocket in catenanes for guest recognition and sensing, the unusual kinetic properties of catenane-coordinated metals for biological and environmental applications, and also the use of the unique dynamics of catenanes in modifying the mechanical and rheological properties of polymeric materials.
Recognition of Biologically and Environmentally Relevant Species
In addition to mechanical bond chemistry, we are also interested in molecular recognition in general. In earlier years, our group has developed a bioinorganic approach for the selective recognition and sensing of small organic molecules that are of biological significance. Inspired by the high efficiency and selectivity of metalloenzymes, we have been developing a biomimetic, metal-based approach for the activity-based sensing of small molecules such as superoxide (Chem. Commun. 2017, 53, 10042), catecholamines (Chem. Sci. 2019, 10, 8519), and ascorbate (Chem. Eur. J. 2020, 26, 8794). A series of fluorescent probes have been developed for the selective detection of the small molecules in biological samples including human plasma and live cells. These smart triggers can also be applied in other triggered-release systems for drug delivery and smart materials.
In addition, we are a member of the Nexus of Rare Neurodegenerative Diseases (NRND), which is a multi-disciplinary research network devoted to understand the fundamentals and develop novel treatment strategies for rare neurodegenerative diseases. We have been developing small molecule inhibitors for toxic proteins and nucleotides that are responsible for neurodegenerative diseases such as Huntington's disease.
