Integrating Replication-Based Selection Strategies in Dynamic Covalent Systems

In the past 15 years, the chemistry of reversible covalent bond formation (dynamic covalent chemistry (DCC)) has been exploited to engineer networks of interconverting compounds known as dynamic combinatorial libraries (DCLs). Classically, the distribution of library components is governed by their relative free energies, and so, processes that manipulate the free energy landscape of the DCL can influence the distribution of library members. Within the same time frame, the design and implementation of molecules capable of copying themselves-so-called replicators-has emerged from the field of template-directed synthesis. Harnessing the nonlinear kinetics inherent in replicator behavior offers an attractive strategy for amplification of a target structure within a DCL and, hence, engendering high levels of selectivity within that library. The instructional nature of replicating templates also renders the combination of replication and DCC a potential vehicle for developing complex reaction networks; a prerequisite for the development of the emerging field of systems chemistry. This Concept article explores the role of kinetically and thermodynamically controlled processes within different DCC frameworks. The effects of embedding a replicating system within these DCC frameworks is explored and the consequences of the different topologies of the reaction network for amplification and selectivity within DCLs is highlighted.