Supramolecular self-assembly by layering orthogonality to program identity, connectivity and conformation

Supramolecular systems derive their structure and function from reversible interactions or bonds that direct components into defined architectures. Natural assemblies such as enzymes, nucleic acids and membranes illustrate how different types of dynamic interactions can act in parallel to control the presence, order, sequence and orientation of assembled components, yet remain independent from one another to enable advanced function. Reproducing this level of control in discrete, artificial systems relies on the same approach. This Review outlines how different reversible interactions found in supramolecular systems - dynamic-covalent bonds, metal-coordination, hydrogen bonding, σ-hole and π-interactions - can be used individually or in concert to program the assembly of sophisticated structures at equilibrium. Emphasis is placed on systems of low symmetry or complex topology, showcasing strategies for generating discrete receptors, capsules, cages, interlocked architectures and foldamers with structural precision.