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This tutorial review outlines the different template strategies that chemists have employed to synthesise knotted molecular topologies. Metal ion coordination, hydrogen bonding and aromatic donor–acceptor interactions have all been used to direct the formation of well-defined crossing points for molecular strands. Advances in the methods used to covalently capture the interwoven structures are highlighted, including the active metal template strategy in which metal ions both organise crossing points and catalyse the bond forming reactions that close the loop to form the topologically complex product. Although most non-trivial knots prepared to date from small-molecule building blocks have been trefoil knots, the first pentafoil knot was recently synthesised. Possible future directions and strategies in this rapidly evolving area of chemistry are discussed.
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