10.1021/ja4067805.s001 Morteza Malakoutikhah Morteza Malakoutikhah Jérôme J.-P. Peyralans Jérôme J.-P. Peyralans Mathieu Colomb-Delsuc Mathieu Colomb-Delsuc Hugo Fanlo-Virgós Hugo Fanlo-Virgós Marc C. A. Stuart Marc C. A. Stuart Sijbren Otto Sijbren Otto Uncovering the Selection Criteria for the Emergence of Multi-Building-Block Replicators from Dynamic Combinatorial Libraries American Chemical Society 2013 material selection criteria replication pathway replicators need library members MW Selection Criteria molecule combinatorial chemistry 5.6 kDa emergence future discovery combinatorial libraries fibril fragmentation Dynamic Combinatorial LibrariesA family macrocycle size tunable ring size 2013-12-11 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Uncovering_the_Selection_Criteria_for_the_Emergence_of_Multi_Building_Block_Replicators_from_Dynamic_Combinatorial_Libraries/2343721 A family of self-replicating macrocycles was developed using dynamic combinatorial chemistry. Replication is driven by self-assembly of the replicators into fibrils and relies critically on mechanically induced fibril fragmentation. Analysis of separate dynamic combinatorial libraries made from one of six peptide-functionalized building blocks of different hydrophobicity revealed two selection criteria that govern the emergence of replicators from these systems. First, the replicators need to have a critical macrocycle size that endows them with sufficient multivalency to enable their self-assembly into fibrils. Second, efficient replication occurs only for library members that are of low abundance in the absence of a replication pathway. This work has led to spontaneous emergence of replicators with unrivalled structural complexity, being built from up to eight identical subunits and reaching a MW of up to 5.6 kDa. The insights obtained in this work provide valuable guidance that should facilitate future discovery of new complex self-replicating molecules. They may also assist in the development of new self-synthesizing materials, where self-assembly drives the synthesis of the very molecules that self-assemble. To illustrate the potential of this concept, the present system enables access to self-assembling materials made from self-synthesizing macrocycles with tunable ring size ranging from trimers to octamers.