Large protein-sized synthetic supramolecular architecture is rare and certainly has not yet achieved the structural and functional complexity of biomolecules. As multiple, identical copies of a few building blocks are repetitively used, a highly symmetrical architecture results with limitations in function. In marked contrast, functional structures in nature are often assembled with high geometric precision from many different building blocks. They cooperate in a complex way realizing energy conversion, mechanical motion or transport phenomena. Beyond self-assembly, the structurally and functionally complex biomolecular machines rely on self-sorting to correctly position all subunits through orthogonal recognition sites. Mimicking such self-sorting processes is a promising strategy for supramolecular synthesis – resulting in higher structural complexity and promising access to a more sophisticated function. The term “integrative self-sorting” was coined to describe the strategy to form well-defined assemblies with well-controlled subunit positions. The key process is the incorporation of two or more orthogonal binding motifs into at least some of the subunits. Modularity and programmability based on orthogonal yet similar binding motifs generate diversity and complexity. Integrative self-sorting is thus inherently related to systems chemistry. Depending on the individual binding motifs, (multi-)stimuli responsiveness can be achieved. When different recognition events en route to the final assembly occur on significantly different time scales, kinetic pathway selection is observed. In this account, we review the modularity, programmability, and emergent properties of integrative self-sorting, emphasizing its utility and perspective for complex supramolecular architectures.

In this tutorial review, different aspects of cooperativity in supramolecular chemistry and their thermodynamic analysis are discussed.

Water is an essential comonomer in a supramolecular polymer that is used as a recyclable, water-activated glue.

Starting from the basis of a simple 4-component self-sorting system of crown ethers and ammonium ions, we design 6 building blocks in which 2 identical or different binding sites are incorporated. These building blocks can be mixed in many different ways to yield quite distinctly different pseudorotaxane assemblies. The self-sorting process integrates all building blocks in specific places so that this approach permits us to exert positional control and can widely influence the resulting assemblies with respect to the details of their structures. At maximum, we report quadruply interlocked species with up to 5 subunits that form specific assemblies. Although NMR methods are limited to the analysis of simpler complexes, ESI-MS and, in particular, tandem mass spectrometry is highly useful to analyze the assemblies' connectivities.