Dynamic self-assembly of supramolecular catalysts from precision macromolecules.

We show the emergence of strong catalytic activity at low concentrations in dynamic libraries of complementary sequence-defined oligomeric chains comprising pendant functional catalytic groups and terminal recognition units. In solution, the dynamic constitutional library created from pairs of such complementary oligomers comprises free oligomers, self-assembled di(oligomeric) macrocycles, and a virtually infinite collection of linear poly(oligomeric) chains. We demonstrate, on an exemplary catalytic system requiring the cooperation of no less than five chemical groups, that supramolecular di(oligomeric) macrocycles exhibit a catalytic turnover frequency ca. 20 times larger than the whole collection of linear poly(oligomers) and free chains. Molecular dynamics simulations and network analysis indicate that self-assembled supramolecular di(oligomeric) macrocycles are stabilized by different interactions, among which chain end pairing. We mathematically model the catalytic properties of such complex dynamic libraries with a small set of physically relevant parameters, which provides guidelines for the synthesis of oligomers capable to self-assemble into functionally-active supramolecular macrocycles over a larger range of concentrations.

Flow-chemistry enabled efficient synthesis of ß-peptides: backbone topology vs. helix formation.

Enantiodiscriminative helix formation was observed for ß-peptide H14 helices. This observation is caused by the synperiplanar orientation of H-O atoms which is more unfavorable than those for H-H interaction. The 1,2 H-O interaction leads to the destruction of the helical structure. The introduction of a double C-C bond in the backbone rules out helix formation.

Continuous-flow retro-Diels-Alder reaction: an efficient method for the preparation of pyrimidinone derivatives.

The syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels-Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved.

Homochirality of ß-Peptides: A Significant Biomimetic Property of Unnatural Systems.

Homochirality, an interesting phenomenon of life, is mainly an unresolved problem and was thought to be a property of living matter. Herein, we show that artificial ß-peptides have the tendency toward homochiral diastereoselective chain elongation. Chain-length-dependent stereochemical discrimination was investigated in the synthesis of foldamers with various side chains and secondary structures. It was found that there is a strong tendency toward the synthesis of homochiral oligomers. The size of the side chain drastically influenced the selectivity of the stereodiscriminative chain-elongation reaction. It is noteworthy that water as the co-solvent increases the selectivity. Such behavior is a novel fundamental biomimetic property of foldamers with a potential of future industrial application.