Two Synthetic Replicators Compete To Process a Dynamic Reagent Pool

Abstract

Complementary building blocks, comprising a set of four aromatic aldehydes and a set of four nucleophiles—three anilines and one hydroxylamine—combine through condensation reactions to afford a dynamic covalent library (DCL) consisting of the eight starting materials and 16 condensation products. One of the aldehydes and, consequently, all of the DCL members derived from this compound bear an amidopyridine recognition site. Exposure of this DCL to two maleimides, Mp and Mm, each equipped with a carboxylic acid recognition site, results in the formation of a series of products through irreversible 1,3-dipolar cycloaddition reactions with the four nitrones present in the DCL. However, only the two cycloadducts in the product pool that incorporate both recognition sites, Tp and Tm, are self-replicators that can harness the DCL as feedstock for their own formation, facilitating their own synthesis via autocatalytic and cross-catalytic pathways. The ability of these replicators to direct their own formation from the components present in the dynamic reagent pool in response to the input of instructions in the form of preformed replicators is demonstrated through a series of quantitative 19F{1H} NMR spectroscopy experiments. Simulations establish the critical relationships between the kinetic and thermodynamic parameters of the replicators, the initial reagent concentrations, and the presence or absence of the DCL and their influence on the competition between Tp and Tm. Thus, we establish the rules that govern the behavior of the competing replicators under conditions where their formation is coupled tightly to the processing of a DCL.