Simultaneous Formation of a Foldamer and a Self-Replicator by Out-of-Equilibrium Dynamic Covalent Chemistry

Area of Science:

• Systems chemistry
• Synthetic biology
• Chemical self-assembly

Background:

• Systems chemistry aims to create life-like molecular systems, requiring control over assembly pathways.
• Dissipative chemical fueling enables the formation of transient structures.

Purpose of the Study:

• To create a synthetic dynamic combinatorial library from a single building block.
• To demonstrate the emergence of self-replicators and foldamers via competing pathways.
• To control the coexistence of these assemblies using dissipative chemistry.

Main Methods:

• Utilized a single, structurally simple building block to form a dynamic combinatorial library.
• Employed fueled chemical reaction cycles to transiently generate foldamers in the presence of self-replicators.
• Controlled pathway partitioning and reaction duration by adjusting chemical fuel concentration.
• Achieved out-of-equilibrium steady states using a continuous stirred tank reactor.

Main Results:

• A single building block yielded both a self-replicator (intermolecular assembly) and a foldamer (intramolecular assembly).
• Foldamer formation was transient and controllable via chemical fueling.
• Adjusting chemical fuel controlled the partitioning of the building block between pathways.
• Stable coexistence of foldamers and self-replicators was achieved out-of-equilibrium, unlike at equilibrium.

Conclusions:

• Connects folding and self-replication in synthetic systems using dissipative out-of-equilibrium chemistry.
• Demonstrates stable coexistence of foldamers and self-replicators from a single building block when energy is supplied.
• Highlights the role of dissipative chemistry in overcoming equilibrium limitations for complex system formation.