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

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.

Triple Stack of a Viologen Derivative in a CB[10] Pair

“…With its largest cavity in the CB family, 16 cucurbit [10]uril 17 (CB [10], Figure 1a) can complex large guests like a porphyrin, 18 ruthenium complexes, 19 large dyes, 20 or triple stranded helicates. 21 With smaller guests, double stacking is observed in CB [10] enabling to control photodimerization 22 or to promote metal-metal interactions. 23 Exploiting charge-transfer interactions between viologens and a naphtalene, three guests were assembled in a quaternary CB [10]Complex.…”

“…However, stacking more than two guests in CB­[ n ] is not trivial. With its largest cavity in the CB family, cucurbit[10]­uril (CB[10], Figure a) can complex large guests such as a porphyrin, fluorescent guests, functionalized pyrenes, or triple-stranded helicates . With smaller guests, double stacking is observed in CB[10], enabling control of photodimerization or promotion of metal–metal interactions .…”

Cucurbit[10]uril‐mediated Supramolecular Assembly for Optically Tunable Dimers and Near White‐light Emissive Materials

“…[35][36][37] For H a -H a'' with a larger Δδ, there should be stronger coordination interactions. One of the carboxyl groups of the bound OPVCOOH coordinated not only with Fe 2 + but also interacted with the carbonyl group of the Q [10] portals, because its chemical shift value of H a'' was bigger than that of bound OPVCOOH and free OPVCOOH. By contrast, Ha', which was also very close to the carboxyl coordination active site, was only weakly affected by the metal interaction.…”

Supramolecular Cylinders Target Bulge Structures in the 5′ UTR of the RNA Genome of SARS‐CoV‐2 and Inhibit Viral Replication**

“…These sites were then identified through ar everse transcription reaction that generates DNAfragments which end at the 1M7 tagged sites and were readily analysed by gel electrophoresis (Figure 3A). Tw op rimers (RT1 and RT2) conjugated with [35] L', [36] and L'' [37] form analogous cylinders that bear further aryl rings on their external surfaces. C) View of the crystal structure of acylinder bound in an RNA 3-way junction cavity from PDB 4JIY [32] showing its unique binding.…”