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.