Design of Subreplicating Systems from an Existing Self-Replicating Diels-Alder Reaction System by Isosteric Replacement.

Abstract

The key feature of non-enzymatic self-replicating systems is the formation of catalytically active ternary complexes in which product templates direct precursors into spatial proximity to allow the formation of new covalent bonds. It is possible to create new replicating species by simply evaluating the ternary active complex of an existing replicating system and applying proper isosteric replacements. In this study, we have evaluated the formerly reported self-replicating Diels-Alder reaction having 61 and 33% selectivity for two diastereomeric replicators. An isosteric replacement on the spacer part connecting recognition and reactive sites of the maleimide component was applied by considering the symmetry of catalytically active ternary complexes, and it was shown that self-replication was conserved. Analysis of the new system showed 77 and 21% diastereoselectivity for the two new replicating species. Seeding experiments indicated autocatalytic activity of both replicators. In other words, both replicators compete with each other by catalyzing their own formation from the same reagent source. Another modification was applied by aiming selective blocking of the autocatalytic cycle of the competing diastereomer. The new system showed a diastereoselectivity of about 94% for the favored replicator. The kinetic data of both systems were analyzed by modeling with SimFit simulations.