A route to mechanically interlocked architectures that requires only a catalytic quantity of template is described. The strategy utilizes the Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes. Chelating the Cu(I) to an endotopic-binding macrocycle means that the metal atom binds to the alkyne and azide in such a way that the metal-mediated bond-forming reaction occurs through the cavity of the macrocycle, forming a rotaxane. Addition of pyridine to the reaction mixture enables the Cu(I) to turn over during the reaction, permitting substoichiometric amounts of the metal to be used. The yields are very high for a rotaxane-forming reaction (up to 94% with stoichiometric Cu(I); 82% with 20 mol % of Cu(I)), and the procedure is practically simple to do (no requirement for an inert atmosphere nor dried or distilled solvents).

Switch it on! The activity of an organocatalytic group incorporated within a rotaxane architecture can be controlled by switching the position of the macrocycle. The system was used to mediate the progress of the Michael addition of an aliphatic thiol to trans‐cinnamaldehyde.

A synthetic approach to rotaxane architectures is described in which metal atoms catalyze covalent bond formation while simultaneously acting as the template for the assembly of the mechanically interlocked structure. This "active-metal" template strategy is exemplified using the Huisgen-Meldal-Fokin Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes (the CuAAC "click" reaction). Coordination of Cu(I) to an endotopic pyridine-containing macrocycle allows the alkyne and azide to bind to metal atoms in such a way that the metal-mediated bond-forming reaction takes place through the cavity of the macrocycle--or macrocycles--forming a rotaxane. A variety of mono- and bidentate macrocyclic ligands are demonstrated to form [2]rotaxanes in this way, and by adding pyridine, the metal can turn over during the reaction, giving a catalytic active-metal template assembly process. Both the stoichiometric and catalytic versions of the reaction were also used to synthesize more complex two-station molecular shuttles. The dynamics of the translocation of the macrocycle by ligand exchange in these two-station shuttles could be controlled by coordination to different metal ions (rapid shuttling is observed with Cu(I), slow shuttling with Pd(II)). Under active-metal template reaction conditions that feature a high macrocycle:copper ratio, [3]rotaxanes (two macrocycles on a thread containing a single triazole ring) are also produced during the reaction. The latter observation shows that under these conditions the mechanism of the Cu(I)-catalyzed terminal alkyne-azide cycloaddition involves a reactive intermediate that features at least two metal ions.

The copper(I)-catalysed azide-alkyne cycloaddition (the CuAAC 'click' reaction) is proving to be a powerful new tool for the construction of mechanically interlocked molecular-level architectures. The reaction is highly selective for the functional groups involved (terminal alkynes and azides) and the experimental conditions are mild and compatible with the weak and reversible intermolecular interactions generally used to template the assembly of interlocked structures. Since the CuAAC reaction was introduced as a means of making rotaxanes by an 'active template' mechanism in 2006, it has proven effective for the synthesis of numerous different types of rotaxanes, catenanes and molecular shuttles by passive as well as active template strategies. Mechanistic insights into the CuAAC reaction itself have been provided by unexpected results encountered during the preparation of rotaxanes. In this tutorial review we highlight the rapidly increasing utility and future potential of the CuAAC reaction in mechanically interlocked molecule synthesis.

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Here, we introduce a 3D-DNA construction method that assembles a minimum number of DNA strands in quantitative yield, to give a scaffold with a large number of single-stranded arms. This DNA frame is used as a core structure to organize other functional materials in 3D as the shell. We use the ring-opening metathesis polymerization (ROMP) to generate block copolymers that are covalently attached to DNA strands. Site-specific hybridization of these DNA-polymer chains on the single-stranded arms of the 3D-DNA scaffold gives efficient access to DNA-block copolymer cages. These biohybrid cages possess polymer chains that are programmably positioned in three dimensions on a DNA core and display increased nuclease resistance as compared to unfunctionalized DNA cages.

The preparation of rotaxanes and other mechanically interlocked molecules by the oriented assembly of ligands around metal ions is a classic demonstration [1] of the utility and effectiveness of template-directed synthesis.[2] However, besides organizing the organic fragments through its preferred coordination geometry, the metal template is usually otherwise passive during such reactions. To exploit the richness of the metals chemistry more fully in synthesis, we recently started to explore a strategy for rotaxane formation in which the metal plays a dual role, acting as both a template for threading and catalyzing covalent-bond formation.[3]Unlike "passive" template methodologies, in which the rotaxane product is normally a better ligand for the metal than the non-interlocked components, this type of "active" template can, in principle, be made to work substoichiometrically. The feasibility of such an approach was first demonstrated [3] using tetrahedral Cu I centers, which is both the most well-established [1b, h, 4] coordination geometry for metal template rotaxane-forming reactions and an extremely structurally tolerant catalyst [5] for the azide-alkyne 1,3-cycloaddition (a so-called "click" reaction [6] ). Herein we report an application of the active-metal template concept to palladium chemistry, which is rather more demanding in terms of template geometry, but somewhat more significant in terms of catalysis.The explosive growth in the number and variety of palladium-catalyzed transformations over the latter part of the 20th century has seen palladium become the workhorse of modern synthetic chemistry.[7] Palladium-catalyzed processes include the formation of CÀO, CÀN, CÀS, and, most notably, C À C bonds. [7] Although Pd II has a square-planar coordination geometry, it has proved possible to use its two-dimensional motif to assemble rotaxanes [8] and catenanes [9] in classical passive template strategies by utilizing steric control over the required crossover point in the third dimension.[10]Macrocycle 1 a (Scheme 1) [9] was chosen as a suitable candidate ligand for developing a palladium active-template rotaxane synthesis. X-ray crystallography of a related palladium(II) [2]catenate shows that the trans-coordinated chloride ligands protrude out of opposite sides of the macrocycle

Supporting information Contents 1. Experimental section: Reagents, methods and equipment 2. Synthesis of PEG-Biotin ROMP monomer 5 3. General procedure for polymerisation 4. Synthesis and characterization of Polymer 6 : (PEG) 3 -(Ir) 10 -(nBu) 10 5. Synthesis and characterization of Polymer 7 : (Bio) 1 -(PEG) 3 -(Ir) 10 -(nBu) 10 6. Synthesis and characterization of Polymer 8 : (BioPEG) 3 -(Ir) 10 -(nBu) 10 7. TEM images of micelles from polymers 6, 7 and 8 8. AFM images of micelles from polymers 6 9. Quantitation of amount of polymer bound to Streptavidin-coated magnetic beads 10. Scheme for microcontact printing of Streptavidin onto glass surfaces 1. Experimental section: Reagents, methods and equipment Reagents and supplies.