Stoichiometry alone can steer supramolecular systems on complex free energy surfaces with high selectivity

Self-assembly enables access to complex molecular architectures but is traditionally confined to structures that represent global minima on the Gibbs energy landscape. We now report that it is possible to access structures other than those with the lowest individual Gibbs energy, while remaining under thermodynamic control. We prepared dynamic combinatorial libraries from two building blocks possessing complementary binding motifs. Depending on the building block stoichiometry, one of three competing self-assembling macrocycles can be formed with remarkable selectivity. By mixing the same two building blocks, we could access a self-replicating octamer, self-assembling into fibers; a hexamer with a precise 4:2 building block stoichiometry, assembling into hexagonally packed fiber bundles; and a tetramer with 1:3 building block ratio affording a [c3]daisy chain pseudorotaxane. Thus, systems chemistry approaches can enhance the versatility of self-assembly by allowing to navigate complex Gibbs energy landscapes to access structures beyond those that are individually the most stable.