Systems chemistry has emerged as a useful paradigm to access structures and phenomena typically exhibited by living systems, including complex molecular systems such as self-replicators and foldamers. As we progress further toward the noncovalent synthesis of life-like systems, and eventually life itself, it is necessary to gain control over assembly pathways. Dissipative chemical fueling has enabled access to stable populations of (self-assembled) structures that would normally form only transiently. Here, we report a synthetic dynamic combinatorial library, made from a single structurally simple building block, from which a self-replicator and a foldamer can emerge along two distinct and competing pathways through an inter- or intramolecular assembly process, respectively. A fueled chemical reaction cycle is then set up to generate the foldamer transiently, in the presence of the self-replicator. The partitioning of the building block between the folding and self-replication pathways and the duration of the fueled reaction cycles are controlled by adjusting the amount of the chemical fuel. An out-of-equilibrium steady state involving the two assemblies could also be achieved by using a continuous stirred tank reactor with inflow and outflow of material. This work connects the domains of folding and self-replication in synthetic systems through dissipative out-of-equilibrium chemistry. It demonstrates that foldamers and self-replicators, formed from the same building block, can stably coexist if the system is continuously supplied with energy, while at equilibrium, the Gibbs phase rule prohibits such coexistence.
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