Bridging β‐Cyclodextrin Prevents Self‐Inclusion, Promotes Supramolecular Polymerization, and Promotes Cooperative Interaction with Nucleic Acids

Abstract

A bridge to assemble: Cyclodextrins bridged with an ammonium linker bearing a hydrophobic substituent can efficiently form supramolecular polymers and avoid the competing self-inclusion and head-to-head processes. Furthermore, the self-assembling cyclodextrin derivative interacts in a highly cooperative manner with DNA, as demonstrated by compaction experiments. It also interacts cooperatively with siRNA and allows its transfection.

The Lord of the NanoRings: Cyclodextrins and the battle against SARS-CoV-2

“…The most important limitation in the use of this technology is the delivery of the RNA-drug to reach the cytoplasm of the target cell maintaining its integrity, since siRNA is highly unstable (half-life < 1 h in human plasma). CDs are well suited to help in this task due to their very low toxicity and versatility to include different chemical modifications (Chaturvedi et al, 2011;Evenou et al, 2018;O'Mahony et al, 2013). CDs have been specifically grafted to self-assemble in the presence of nucleotides thus encapsulating and so protecting them from degradation (Mellet et al, 2011;Sallas and Darcy, 2008).…”

From Interaction to Function in DNA‐Templated Supramolecular Self‐Assemblies

“…Recently, Sollogoub, Bouteiller and colleagues reported the supramolecular polymerization of β‐cyclodextrin (β‐CD) derivatives along a DNA template . The β‐CD is designed in such a way that it is bridged on the lower rim, and an adamantane is attached with a linker to one amino group at the edge of the bridge (Figure ).…”

“…Isodesmic supramolecular polymerization occurs by self‐assembly in the mM range, whereas cooperative supramolecular polymerization occurs in the μM range presence of a DNA template. Adapted with permission from reference . Copyright 2018 Wiley‐VCH.…”

“…Remarkably, the cationic bridged β‐CD system discussed above (section 4.1, Figure ), developed by Bouteiller, Sollogoub and co‐workers, was shown to efficiently complex siRNA by gel electrophoresis experiments . The researchers tested the ability of the supramolecular self‐assemblies to transfect cells, using a GL3 siRNA (directed against the expression of luciferase) and HEK‐293 cells, expressing the firefly luciferase GL3.…”

Construction of Pillar[5]arene Tetramer‐Based Cross‐Linked Supramolecular Polymers through Hierarchical Charge‐Transfer and Host‐Guest Interactions

“…Generally speaking, the interaction between bridged hosts and guests is the most efficient way to construct crossliked supramolecular polymers, such as bridged cyclodextrin which has been the most widely studied due to excellent receptors for molecular recognition, of the corresponding guests and building blocks for functional materials. [12][13][14] Pillar [5]arene, recognized as a new generation of macrocyclic host molecules, [15][16][17] recently underwent a rapid development to build functional supramolecular materials due to possessing simple symmetric rigid structures and facile functionalization with multifarious substituents. [18,19] Until now, many existing bridged pillararene oligomers such as dimers, [20,21] trimers, [22,23] tetramer [24,25] and even hexamer [26] were designed and fabricated to construct cross-linked supramolecular polymers.…”