Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding

Catherine A J Hooper, Lucia Cardo, James S Craig, Lazaros Melidis, Aditya Garai, Ross T Egan, Viktoriia Sadovnikova, Florian Burkert, Louise Male, Nikolas J Hodges, Douglas F Browning, Roselyne Rosas, Fengbo Liu, Fillipe V Rocha, Mauro A Lima, Simin Liu, David Bardelang, Michael J Hannon

Research output: Contribution to journalArticlepeer-review

Abstract

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

Original languageEnglish
Pages (from-to)20651-20660
Number of pages10
JournalJournal of the American Chemical Society
Volume142
Issue number49
Early online date20 Nov 2020
DOIs
Publication statusPublished - 9 Dec 2020

Bibliographical note

This is an open access article published under a Creative Commons Attribution (CC-BY)
License, which permits unrestricted use, distribution and reproduction in any medium,
provided the author and source are cited.

Keywords

  • Bridged-Ring Compounds/chemistry
  • Coordination Complexes/chemistry
  • DNA/chemistry
  • Imidazoles/chemistry
  • Ligands
  • Metals/chemistry
  • Nanostructures/chemistry
  • Rotaxanes/chemistry

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