Functionalization of a [2]Catenane with Donor-Acceptor Chromophores Using a Metal Template and Click Reactions.

Synthesizing molecules with significant topological features, such as catenanes, tailored with specific groups to confer desired functionality, is essential for investigating various properties arising from the entanglement due to mechanical bonds. This investigation can pave the way for uncovering novel functional materials employing mechanically interlocked molecules (MIMs). In this direction, we have synthesized a p-donor (D) and p-acceptor (A) functionalized [2]catenane using a non-labile Co(III) metal ion as a template with pyridine-diamide templating center and utilizing click reaction for ring-closing. The donor group is a fluorene derivative, and the acceptor is a benzophenazine derivative, commonly employed in synthesizing conjugated polymers for various optoelectronic devices. Synthetically, the acceptor group was introduced into a macrocycle with a pyridine diamide unit. It was then threaded with a ligand having alkyne terminals to obtain the desired [2]pseudorotaxane utilizing cobalt ion as a template. Ring-closing was then performed with a di-azide functionalized molecule with the donor chromophore. The desired D-A functionalized [2]catenane is obtained after demetalation. All the starting materials, macrocycle, and entangled structures have been characterized by 1H-NMR, 13C-NMR, and mass spectroscopy. Some of these materials are also characterized by single-crystal X-ray analysis. The photophysical properties are studied by UV-visible and fluorescence spectroscopy.

Template Assisted Synthesis of Linear [5]Catenane by Post-Functionalization of Templated [2]Catenane and Using Click Reaction.

Polymers with all mechanically interlocked rings, such as linear [n]catenanes, have great potential as functional materials due to possible higher degrees of freedom that may contribute to their flexibility but remain elusive. All the synthetic methods used to prepare such a polymer yield mixtures of products. In the absence of higher molecular weight linear [n]catenanes, emphasis on synthesizing low molecular weight oligomers is being pursued. Here, we have described the synthesis of a linear [5]catenane by post-functionalizing a Co(III) templated [2]catenane having a pyridine-diamide unit free for further metal ion coordination. Two molecules were synthesized with suitable threading groups: one, two terminal azide groups, and two, with two terminal alkyne groups to form two [3]pseudorotaxane utilizing Co(III) coordination. These units were then joined, forming a macrocycle, using click reaction, giving the desired metalated linear [5]catenane in 40 % yield. Removal of metal ions leads to linear [5]catenane. In addition, the formation of linear [3] and [2]catenane are also observed. All synthesized structures have been isolated by column chromatographic technique and characterized by 1H-NMR, 13C-NMR, and mass spectroscopy.

Triply Interlocked [2]catenanes: Rational Synthesis, Reversible Conversion Studies and Unprecedented Application in Photothermal Responsive Elastomer.

Triply interlocked [2]catenane complexes featuring two identical, mechanically interlocked units are extraordinarily rare chemical compounds, whose properties and applications remain open to detailed studies. Herein, we introduce the rational design of a new ligand precursor, L1, suitable for the synthesis of six triply interlocked [2]catenanes by coordination-driven self-assembly. The interlocked compounds can be reversibly converted into the corresponding simple triangular prism metallacage by addition of H2O or DMF solvents to their CH3OH solutions, thereby demonstrating the importance of π⋅⋅⋅π stacking and hydrogen bonding interactions in the formation of triply interlocked [2]catenanes. Moreover, extensive studies have been conducted to assess the remarkable photothermal conversion performance. Complex 6 a, exhibiting outstanding photothermal conversion performance (conversion efficiency in solution : 31.82 %), is used to prepare novel photoresponsive elastomer in combination with thermally activated liquid crystal elastomer. The resultant material displays robust response to near-infrared (NIR) laser and the capability of completely reforming the shape and reversible actuation, paving the way for the application of half-sandwich organometallic units in photo-responsive smart materials.

Water and Air Stable Copper(I) Complexes of Tetracationic Catenane Ligands for Oxidative C-C Cross-Coupling.

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

Dynamic control of circumrotation of a [2]catenane by acid-base switching.

Dynamic control of the motion in a catenane remains a big challenge as it requires precise design and sophisticated well-organized structures. This paper reports the design and synthesis of a donor-acceptor [2]catenane through mechanical interlocking, employing a crown ether featuring two dibenzylammonium salts on its side arms as the host and a cyclobis(paraquat-p-phenylene) (CBPQT ⋅ 4PF6) ring as the guest molecule. By addition of external acid or base, the catenane can form self-complexed or decomplexed compounds to alter the cavity size of the crown ether ring, consequently affecting circumrotation rate of CBPQT ⋅ 4PF6 ring of the catenane. This study offers insights for the design and exploration of artificial molecular machines with intricate cascading responsive mechanisms.

Template Assisted One-Pot Synthesis of [2], Linear [3], and Radial [4]Catenane via Click Reaction.

Design and synthesis of higher order catenane are unexpectedly complex and involve precise cooperation among the precursors overcoming competing and opposing interactions. We achieved synthesis of [2], linear [3], radial [4] in a one-pot reaction by consecutive ring closing through click reactions. This synthesis gave three isolable products due to two, four, and six-click reactions between suitable coupling partners. Yields of the isolate templated-catenane decrease from lower to higher-ordered catenane (40 %, 12 %, and 4 %), probably due to the bite angle as well as the flexibility of the reacting partners. Removal of templating cobalt(III) ion leads to the formation of fully organic [2], linear [3], and radial [4]catenane. These synthesized catenanes were purified by column chromatography and characterized by 1H-NMR, 13C-NMR, and ESI-MS spectroscopy. The synthesized catenanes have free binding sites suitable for post-functionalization and may be used for the synthesis of higher-ordered catenane.

Exploiting the Mechanical Bond Effect for Enhanced Molecular Recognition and Sensing.

The ubiquity of charged species in biological and industrial processes has resulted in ever-increasing interest in their selective recognition, detection, and environmental remediation. Building on the established coordination chemistry principles of the chelate and macrocyclic effects, and host preorganization, supramolecular chemists seek to construct specific 3D binding cavities reminiscent of biotic systems to enhance host-guest binding affinity and selectivity. Mechanically interlocked molecules (MIMs) present a wholly unique platform for synthetic host design, wherein topologies afforded by the mechanical bond enable the decoration of 3D cavities for non-covalent interactions with a range of target guest geometries. Notably, MIM host systems exhibit mechanical bond effect augmented affinities and selectivities for a variety of charged guest species, compared to non-interlocked acyclic and macrocycle host analogs. Furthermore, the modular nature of MIM synthesis facilitates incorporation of optical and electrochemical reporter groups, enabling fabrication of highly sensitive and specific molecular sensors. This review discusses the development of recognition and sensing MIMs, from the first reports in the late 20th century through to the present day, delineating how their topologically preorganized and dynamic host cavities enhance charged guest recognition and sensing, demonstrating the mechanical bond effect as a potent tool in future chemosensing materials.

Noncovalent Modification of Cycloparaphenylene by Catenane Formation Using an Active Metal Template Strategy.

The active metal template (AMT) strategy is a powerful tool for the formation of mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes, allowing the synthesis of a variety of MIMs, including π-conjugated and multicomponent macrocycles. Cycloparaphenylene (CPP) is an emerging molecule characterized by its cyclic π-conjugated structure and unique properties. Therefore, diverse modifications of CPPs are necessary for its wide application. However, most CPP modifications require early stage functionalization and the direct modification of CPPs is very limited. Herein, we report the synthesis of a catenane consisting of [9]CPP and a 2,2'-bipyridine macrocycle as a new CPP analogue that contains a reliable synthetic scaffold enabling diverse and concise post-modification. Following the AMT strategy, the [9]CPP-bipyridine catenane was successfully synthesized through Ni-mediated aryl-aryl coupling. Catalytic C-H borylation/cross-coupling and metal complexation of the bipyridine macrocycle moiety, an effective post-functionalization method, were also demonstrated with the [9]CPP-bipyridine catenane. Single-crystal X-ray structural analysis revealed that the [9]CPP-bipyridine catenane forms a tridentated complex with an Ag ion inside the CPP ring. This interaction significantly enhances the phosphorescence lifetime through improved intermolecular interactions.

Catenane and Rotaxane Synthesis from Cucurbit[6]uril-Mediated Azide-Alkyne Cycloaddition.

The chemistry of mechanically interlocked molecules (MIMs) such as catenane and rotaxane is full of new opportunities for the presence of a mechanical bond, and the efficient synthesis of these molecules is therefore of fundamental importance in realizing their unique properties and functions. While many different types of preorganizing interactions and covalent bond formation strategies have been exploited in MIMs synthesis, the use of cucurbit[6]uril (CB[6]) in simultaneously templating macrocycle interlocking and catalyzing the covalent formation of the interlocked components is particularly advantageous in accessing high-order catenanes and rotaxanes. In this review, catenane and rotaxane obtained from CB[6]-catalyzed azide-alkyne cycloaddition will be discussed, with special emphasis on the synthetic strategies employed for obtaining complex [n]rotaxanes and [n]catenanes, as well as their properties and functions.

Solvent-Controlled Quadruple Catenation of Giant Chiral [8+12] Salicylimine Cubes Driven by Weak Hydrogen Bonding.

Mechanically interlocked structures are fascinating synthetic targets and the topological complexity achieved through catenation offers numerous possibilities for the construction of new molecules with exciting properties. In the structural space of catenated organic cage molecules, only few examples have been realized so far, and control over the catenation process in solution is still barely achieved. Herein, we describe the formation of a quadruply interlocked catenane of giant chiral [8+12] salicylimine cubes. The formation could be controlled by the choice of solvent used in the reaction. The interlocked structure was unambiguously characterized by single crystal X-ray diffraction and weak hydrogen bonding was identified as a central driving force for the catenation. Furthermore, scrambling experiments using partially deuterated cages were performed, revealing that the catenane formation occurs through mechanical interlocking of preformed single cages.

Stimuli-Responsive Catenane-Based Catalysts.

Rotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli-responsive CuI -complexed [2]catenanes as OFF/ON catalysts for the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The encapsulation of the CuI ion inside the [2]catenanes inhibits its ability to catalyze the formation of triazoles. In contrast, the controlled opening of the two macrocycles induces the breaking of the mechanical bond, thereby restoring the catalytic activity of the CuI ion for the CuAAC reaction. Such OFF/ON catalysts can be involved in signal amplification processes with various potential applications.

A single-domain protein catenane of dihydrofolate reductase.

A single-domain protein catenane refers to two mechanically interlocked polypeptide rings that fold synergistically into a compact and integrated structure, which is extremely rare in nature. Here, we report a single-domain protein catenane of dihydrofolate reductase (cat-DHFR). This design was achieved by rewiring the connectivity between secondary motifs to introduce artificial entanglement and synthesis was readily accomplished through a series of programmed and streamlined post-translational processing events in cells without any additional in vitro reactions. The target molecule contained few exogenous motifs and was thoroughly characterized using a combination of ultra-performance liquid chromatography-mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, protease cleavage experiments and ion mobility spectrometry-mass spectrometry. Compared with the linear control, cat-DHFR retained its catalytic capability and exhibited enhanced stability against thermal or chemical denaturation due to conformational restriction. These results suggest that linear proteins may be converted into their concatenated single-domain counterparts with almost identical chemical compositions, well-preserved functions and elevated stabilities, representing an entirely new horizon in protein science.

A Conjugated Covalent Template Strategy for All-Benzene Catenane Synthesis.

Mechanically interlocked molecules based on oligoparaphenylene-derived nanohoops, particularly those without heteroatoms, are synthetically challenging and topologically intriguing targets. Herein, a π-conjugated covalent template strategy based on azo group has been developed, which features dual intramolecular macrocyclizations directed by a tetra-substituted azobenzene core, followed by traceless removal of the azo linker. Employing this strategy, the efficient synthesis of a novel all-benzene [2]catenane consisting of meta-cycloparaphenylenes has been accomplished.

Topologically-Interlocked Minicircles as Probes of DNA Topology and DNA-Protein Interactions.

DNA minicircles exist in biological contexts, such as kinetoplast DNA, and are promising components for creating functional nanodevices. They have been used to mimic the topological features of nucleosomal DNA and to probe DNA-protein interactions such as HIV-1 and PFV integrases, and DNA gyrase. Here, we synthesized the topologically-interlocked minicircle rotaxane and catenane inside a frame-shaped DNA origami. These minicircles are 183 bp in length, constitute six individual single-stranded DNAs that are ligated to realize duplex interlocking, and adopt temporary base pairing of single strands for interlocking. To probe the DNA-protein interactions, restriction reactions were carried out on DNAs with different topologies such as free linear duplex or duplex constrained inside origami and free or topologically-interlocked minicircles. Except the free linear duplex, all tested structures were resistant to restriction digestion, indicating that the topological features of DNA, such as flexibility, curvature, and groove orientation, play a major role in DNA-protein interactions.

Rational Design and Integrative Assembly of Heteromeric Metalla[2]Catenanes Featuring Cp*Ir/Rh Fragments.

We report a design strategy for integrative assembly of heteromeric [2]catenanes. The design focuses on the shape and functional group match of two different metalla-rectangles. A series of dipyridyl ligands with different lengths, widths and functional groups were designed and used for assembly experiments. Six heteromeric [2]catenanes were obtained both by direct mixture of two pre-assembled metalla-rectangles and one-pot three-component self-assembly. Multiple analytic methods were employed to characterize the catenanes, including single crystal X-ray diffraction analysis, NMR spectroscopy, mass spectroscopy and elemental analysis.

Macrocycle Dynamics in a Branched [8]Catenane Controlled by Three Different Stimuli in Three Different Regions.

A branched [8]catenane from an efficient one-pot synthesis (72 % HPLC yield, 59 % isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril-mediated azide-alkyne cycloaddition (CBAAC) for ring-closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non-influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid-base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non-obvious supramolecular interactions in the synthesis of high-order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.

Self-Assembly Synthesis of a [2]Catenane CoII Single-Molecule Magnet.

We describe herein the self-assembly synthesis of an octanuclear CoII [2]catenane {[Co4 (H2 L)6 ]2 16+ } formed by the mechanical interlocking of two {[Co4 (H2 L)6 ]8+ } rectangles of unprecedented topology. Subtle manipulation of the synthetic conditions allows the isolation of a mixed-valence [Co2 III /Co2 II ]10+ non-catenated rectangle. The CoII centers in the [2]catenane exhibit slow relaxation of their magnetic moment, i. e. single-molecule magnet properties, dominated by quantum tunneling and Raman relaxation processes. This work shows that metallo-supramolecular chemistry can precisely control the organization of single-molecule magnets in topologically complex arrangements.

Self-Assembly of [3]Catenane and [4]Catenane Based on Neutral Organometallic Scaffolds.

Transition metal-mediated templating and self-assembly have shown great potential to construct mechanically interlocked molecules. Herein, we describe the formation of the bimetallic [3]catenane and [4]catenane based on neutral organometallic scaffolds via the orthogonality of platinum-to-oxygen coordination-driven self-assembly and copper(I) template-directed strategy of a [2]pseudorotaxane. The structures of these bimetallic [3]catenane and [4]catenane were characterized by multinuclear NMR {1H and 31P} spectroscopy, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), and PM6 semiempirical molecular orbital theoretical calculations. In addition, single-crystal X-ray analyses of the [3]catenane revealed two asymmetric [2]pseudorotaxane units inside the metallacycle. It was discovered that tubular structures were formed through the stacking of individual [3]catenane molecules driven by the strong π-π interactions.

Protein Conjugation via SpyStapler-Mediated SpyTag/BDTag Coupling.

Genetically encoded peptide-protein coupling reactions, such as the SpyTag/SpyCatcher chemistry, are recent additions to the expanding toolbox of protein bioconjugation. The alternative three-component ligation system, e.g., SpyStapler-mediated SpyTag/BDTag coupling, retains most advantages of the Tag/Catcher chemistry, yet requires only two short peptide tags in the genetic fusion for side-chain ligation. Not only does this facilitate the construction of large protein conjugates directly from as-expressed protein components with minimal disruption to their function, but it also provides an entirely new mode of bioconjugation via mechanical bonding, which could impart additional functional benefits such as improved activity and enhanced stability to the conjugate. Such features are attractive for improving the pharmacokinetic performance of protein therapeutics. Herein we describe protocols for SpyStapler-mediated SpyTag/BDTag coupling for protein bioconjugation. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Conjugation via isopeptide bond Support Protocol: Purification by size-exclusion chromatography Basic Protocol 2: Conjugation via mechanical bond.