Light-Mediated Interconversion between a Foldamer and a Self-Replicator

J Am Chem Soc. 2024 Dec 11;146(49):33395-33402. doi: 10.1021/jacs.4c09114. Epub 2024 Nov 26.

Abstract

Self-replicating molecules and well-defined folded macromolecules are of great significance in the emergence and evolution of life. How they may interconnect and affect each other remains largely elusive. Here, we demonstrate an abiotic system where a single building block can oligomerize to yield either a self-replicating molecule or a foldamer. Specifically, agitation of a disulfide-based dynamic combinatorial library at moderately elevated pH channels it selectively into a self-replicating hexamer assembled into fibers, after passing through a period where a 15-subunit macrocyclic foldamer existed transiently. Without mechanoagitation or at lower pH, the formation of hexamer fiber is suppressed, resulting in the accumulation of the 15mer foldamer. Foldamer and self-replicator can be interconverted in response to external stimuli, including agitation and a change in pH. Furthermore, upon the addition of a photoacid, the pH of the medium can be controlled by irradiation, driving the switching between replicator and foldamer and allowing a dissipative out-of-equilibrium state to be accessed, using light as a source of energy.