Active metal template synthesis is a powerful new strategy for the construction of rotaxanes, catenanes and other mechanically interlocked molecular structures. The key feature is that the metal plays a dual role during the assembly of the interlocked architecture, acting as both a template for entwining or threading the components and as a catalyst for capturing the interlocked final product by covalent bond formation. Unlike traditional “passive” metal template methods to rotaxanes and catenanes, permanent recognition motifs are not required on each of the components to be interlocked (i.e., the assembly can be traceless) and the template can often be used in sub-stoichiometric quantities. Since its inception in 2006, a rapidly growing number of different metal-catalysed reactions have proven suitable for the active metal template synthesis of both rotaxanes and catenanes, including the copper(I)-catalysed terminal alkyne–azide cycloaddition (the CuAAC “click” reaction), palladium- and copper-catalysed alkyne homocouplings and heterocouplings, and palladium-catalysed oxidative Heck couplings and Michael additions. In addition to simple rotaxanes and catenanes, the synthetic strategy has been used to construct switchable molecular shuttles with weak intercomponent interactions (a requirement for fast shuttling) and to provide insight into the mechanisms of transition metal-catalysed reactions. In this tutorial review we highlight the utility and potential of the early examples of the active metal template strategy in mechanically interlocked molecule synthesis.

Metallosupramolecular cages are an emerging, but as of yet relativity unexplored, drug delivery vector. Herein we show that discrete dipalladium(II) molecular cages of the formula [Pd₂L₄](X)₄ can be quantatively self-assembled from a simple tripyridyl ligand (2,6-bis(pyridin-3-ylethynyl)pyridine) and [Pd(CH₃CN)₄](X)₂ (X = BF₄ ⁻ or SbF₆ ⁻). The cages have been fully characterised using ¹H, ¹³C and DOSY NMR spectroscopy, elemental analysis, IR spectroscopy, and high resolution electrospray mass spectrometry (HR-ESMS). Additionally, the molecular structure of the [Pd₂L₄](SbF₆)₄ cage was confirmed unequivocally using X-ray diffraction. These [Pd₂L₄](X)₄ cages are stimuli-responsive and can be reversibly disassembled/reassembled upon the addition/removal of suitable competing ligands. The central cavities of the [Pd₂L₄](X)₄ cages are lined with four hydrogen bond accepting pyridine units which enable the encapsulation of two cisplatin molecules within the metallosupramolecular architecture through hydrogen bonding interactions between the cage and the amine ligands of the cisplatin guest. The structure of the [Pd₂L₄⊃(cisplatin)₂](BF₄)₄ host–guest adduct has been confirmed by ¹H NMR spectroscopy, HR-ESMS and X-ray crystallography. Additionally we have demonstrated that the cage–cisplatin host–guest adduct can be quantatively disassembled upon the addition of a competing ligand, releasing the cisplatin guest. This is the first crystallographically characterised example of a discrete metallosupramolecular cage encapsulating an FDA-approved inorganic drug molecule. This host–guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics.

A one pot, multicomponent CuAAC reaction has been exploited for the safe generation of alkyl, benzyl or aryl linked polydentate pyridyl-1,2,3-triazole ligands from their corresponding halides, sodium azide and alkynes in excellent yields. The ligands have been fully characterised by elemental analysis, HR-ESMS, IR, ¹H and ¹³C NMR and in two cases the structures were confirmed by X-ray crystallography. Additionally, we have examined the Ag(I) coordination chemistry of these ligands and found, using HR-ESMS, ¹H NMR, and X-ray crystallography, that both discrete and polymeric metallosupramolecular architectures can be formed.