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.

β-Cyclodextrin conjugated to adamantane forms self-inclusion complexes instead of supramolecular polymers.

Dedicated to Professor Pierre Sinaþ on the occasion of his 80th birthday It is still ag reat challenge to imitate naturesa bility to form cooperative self-assembled structures using entirely artificial molecular tools and to confer them with properties.Here we show that cyclodextrins bridged by an ammonium linker with ah ydrophobic substituent efficiently form supramolecular polymers at millimolar concentrations and avoid the competing self-inclusion and head-to-head processes.N otably,s uch assembly can occur at micromolecular concentrations in the presence of genomic DNA, thereby resulting in an efficient compaction of DNAt hat is reversible upon addition of ac ompetitive guest and demonstrating their highly cooperative interaction. We finally show that the supramolecular polymer also cooperatively interacts with siRNAa nd allows its transfection.Cooperative self-assembly [1][2][3] is ap owerful tool to construct elaborate architectures in ab ottom-up approach. For example,n ature heavily relies on cooperativity to build the highly complex components of organisms from smaller units. [4] As imple archetypical example of such constructs is the tobacco mosaic virus (TMV), which is formed from only two cooperatively interacting partners:acoat protein and an ucleic acid (NA) template.T he principle feature of the complex assembly process is that the coat protein assembles only in small entities unless the NA is present and induces its full coverage in ah ighly cooperative manner.I nr everse, Supportinginformation and the ORCID identification number for some of the authors of this article can be found under: https://doi.

Regioselective di‐functionalization of a cyclodextrin allows hydrophobic domains to be directed in a geometrically controlled manner. This controlled orientation ultimately gives access to an original hierarchical assembly in the solid state. This assembly spans over three levels of hierarchy which are governed by synergistic host‐guest inclusions, directed hydrophobic effect and hydrogen bonding. This combination of interactions precisely positioned in space through regioselective functionalization of a cyclodextrin creates a porous organic architecture.