Simultaneous Formation\nof a Foldamer and a Self-Replicator\nby Out-of-Equilibrium Dynamic Covalent Chemistry

Systems chemistry has emerged as a useful paradigm to\naccess structures\nand phenomena typically exhibited by living systems, including complex\nmolecular systems such as self-replicators and foldamers. As we progress\nfurther toward the noncovalent synthesis of life-like systems, and\neventually life itself, it is necessary to gain control over assembly\npathways. Dissipative chemical fueling has enabled access to stable\npopulations of (self-assembled) structures that would normally form\nonly transiently. Here, we report a synthetic dynamic combinatorial\nlibrary, made from a single structurally simple building block, from\nwhich a self-replicator and a foldamer can emerge along two distinct\nand competing pathways through an inter- or intramolecular assembly\nprocess, respectively. A fueled chemical reaction cycle is then set\nup to generate the foldamer transiently, in the presence of the self-replicator.\nThe partitioning of the building block between the folding and self-replication\npathways and the duration of the fueled reaction cycles are controlled\nby adjusting the amount of the chemical fuel. An out-of-equilibrium\nsteady state involving the two assemblies could also be achieved by\nusing a continuous stirred tank reactor with inflow and outflow of\nmaterial. This work connects the domains of folding and self-replication\nin synthetic systems through dissipative out-of-equilibrium chemistry.\nIt demonstrates that foldamers and self-replicators, formed from the\nsame building block, can stably coexist if the system is continuously\nsupplied with energy, while at equilibrium, the Gibbs phase rule prohibits\nsuch coexistence.