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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
Additional Information: 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.
Uncontrolled Keywords: Bridged-Ring Compounds/chemistry,Coordination Complexes/chemistry,DNA/chemistry,Imidazoles/chemistry,Ligands,Metals/chemistry,Nanostructures/chemistry,Rotaxanes/chemistry
Publication ISSN: 1520-5126
Last Modified: 01 Jul 2024 16:23
Date Deposited: 14 Jan 2022 13:40
Full Text Link:
Related URLs: ... 21/jacs.0c07750 (Publisher URL)
PURE Output Type: Article
Published Date: 2020-12-09
Published Online Date: 2020-11-20
Accepted Date: 2020-07-18
Authors: Hooper, Catherine A J
Cardo, Lucia
Craig, James S
Melidis, Lazaros
Garai, Aditya
Egan, Ross T
Sadovnikova, Viktoriia
Burkert, Florian
Male, Louise
Hodges, Nikolas J
Browning, Douglas F (ORCID Profile 0000-0003-4672-3514)
Rosas, Roselyne
Liu, Fengbo
Rocha, Fillipe V
Lima, Mauro A
Liu, Simin
Bardelang, David
Hannon, Michael J



Version: Published Version

License: Creative Commons Attribution

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