Directing self-assembly processes out-of-equilibrium to yield kinetically trapped materials with well-defined dimensions remains a considerable challenge. Kinetically controlled assembly of self-synthesizing peptide-functionalized macrocycles through a nucleation-growth mechanism is reported. Spontaneous fiber formation in this system is effectively shut down as most of the material is diverted into metastable non-assembling trimeric and tetrameric macrocycles. However, upon adding seeds to this mixture, well-defined fibers with controllable lengths and narrow polydispersities are obtained. This seeded growth strategy also allows access to supramolecular triblock copolymers. The resulting noncovalent assemblies can be further stabilized through covalent capture. Taken together, these results show that self-synthesizing materials, through their interplay between dynamic covalent bonds and noncovalent interactions, are uniquely suited for out-of-equilibrium self-assembly.

With the advent of reversible covalent chemistry the study of the interplay between covalent bond formation and noncovalent interactions has become increasingly relevant. Here we report that the interplay between reversible disulfide chemistry and self-assembly can give rise either to molecular diversity, i.e., the emergence of a unprecedentedly large range of macrocycles or to molecular specificity, i.e., the autocatalytic emergence of a single species. The two phenomena are the result of two different modes of self-assembly, demonstrating that control over self-assembly pathways can enable control over covalent bond formation.

Directing self-assembly processes out-of-equilibrium to yield kinetically trapped materials with well-defined dimensions remains ac onsiderable challenge.K inetically controlled assembly of self-synthesizing peptide-functionalized macrocycles through an ucleation-growth mechanism is reported. Spontaneous fiber formation in this system is effectively shut down as most of the material is diverted into metastable non-assembling trimeric and tetrameric macrocycles.H owever,u pon adding seeds to this mixture,w elldefined fibers with controllable lengths and narrowp olydispersities are obtained. This seeded growth strategy also allows access to supramolecular triblockc opolymers.T he resulting noncovalent assemblies can be further stabilized through covalent capture.T aken together,t hese results show that selfsynthesizing materials,t hrough their interplay between dynamic covalent bonds and noncovalent interactions,a re uniquely suited for out-of-equilibrium self-assembly. [1] have attracted much recent attention and are applied in fields ranging from self-healing materials [1i] to molecular electronics. [1c,m] Most supramolecular polymers are produced by thermodynamically controlled self-assembly,allowing access to only asingle state involving assemblies with typically abroad and strongly concentrationdependent length distribution. [1f, 2] In contrast, kinetic control of self-assembly pathways [3] can allow access to one of multiple kinetically trapped states,w hile starting from the same precursors and may also enable control over the dimensions and structure of the resulting assemblies.Through their analogy with initiation-propagation mechanisms in living polymerization, nucleation-growth mechanisms [4] based on noncovalent interactions have the potential of producing assemblies of well-defined lengths.C ontrol over assembly length is important, as length dictates rheological and other physical properties of polymeric products. [1k] Whereas in traditional covalent polymer chemistry many polymerization strategies have been developed aimed at producing polymers with narrow polydispersities,c ontrol over dimensions remains rare in colloidal [5] and supramolecular self-assembly [6] and are unprecedented for self-synthesizing materials. [7] Moreover,for supramolecular polymerization control over size and polydispersity of the nuclei, prevention of spontaneous nucleation, and the stability of the resulting materials remain major challenges.I np rinciple,s elf-synthesizing materials [7] should allow excellent control over nucleation. In self-synthesizing materials,t he assembly of the material from its molecular constituents drives the synthesis of more of these constituents from ap ool of interconverting molecules.If, prior to assembly,the self-assembling molecule is only am inor component of the interconverting pool, then spontaneous nucleation of the assembly process should be slow and the assembly process may be triggered by seeding. Supramolecular(bio)polymersWe now demonstrate that aself-synthesizing material t...

Our knowledge regarding the early steps in the formation of evolvable life and what constitutes the minimal molecular basis of life remains far from complete. The recent emergence of systems chemistry reinvigorated the investigation of systems of self-replicating molecules to address these questions. Most of these studies focus on single replicators and the effects of replicators on the emergence of other replicators remains under-investigated. Here we show the cross-catalyzed emergence of a novel self-replicator from a dynamic combinatorial library made from a threonine containing peptide building block, which, by itself, only forms trimers and tetramers that do not replicate. Upon seeding of this library with different replicators of different macrocycle size (hexamers and octamers), we observed the emergence of hexamer replicator consisting of six units of the threonine peptide only when it is seeded with an octamer replicator containing eight units of a serine building block. These results reveal for the first time how a new replicator can emerge in a process that relies critically on the assistance by another replicator through cross-catalysis and that replicator composition is history dependent.

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present.