# Supramolecular assembly properties of a mixed-sequence recognition-encoded melamine oligomer

## TL;DR

This paper studies how a specific melamine-based molecule folds and interacts with itself, revealing insights into its assembly behavior in solution.

## Contribution

The study introduces a self-complementary REMO with a DADA sequence and explores its folding and dimerization behavior.

## Key findings

- DADA forms a dimeric complex in chloroform with reduced stability compared to shorter oligomers.
- The folded state with intramolecular interactions is significantly populated in DADA.
- The macrocyclic duplex dominates at millimolar concentrations after covalent trapping.

## Abstract

Recognition-encoded melamine oligomers (REMO) are composed of an alternating piperazine-triazine backbone and side-chains equipped with either a H-bond donor (phenol, D) or a H-bond acceptor (phosphine oxide, A). Complementary homo-oligomers form stable duplexes in organic solvents, due to intermolecular base-pairing interactions between the phenol and phosphine oxide side-chains. For mixed-sequence oligomers, the major pathway that competes with duplex formation is folding due to intramolecular base-pairing interactions. Automated solid phase synthesis was used to prepare the self-complementary REMO DADA, and this oligomer was used to investigate the competition between intermolecular and intramolecular H-bonding interactions. Isothermal titration calorimetry in chloroform showed that DADA forms a dimeric complex, but with reduced stability compared with the duplexes formed by shorter oligomers. The results indicate that a folded state with intramolecular interactions between the two terminal recognition units is significantly populated. The dimeric complex formed at higher concentrations could involve the interaction of two folded oligomers in a kissing stem-loops structure, or the oligomer could unfold to give the duplex with four intermolecular base-pairs. One end of the oligomer was equipped with an azide and the other with an alkyne, so that the dimeric complex could be covalently trapped using copper-catalysed azide–alkyne cycloaddition reactions. The major product was the macrocyclic duplex with small amounts of the macrocyclic single-strand, which shows that the DADA·DADA duplex dominates at millimolar concentrations. Understanding the propensity of the REMO architecture to fold will help guide the future design principles for synthesis of more complex functional assemblies.

The self-complementary REMO with sequence DADA was prepared by automated solid phase synthesis. Folding due to intramolecular H-bonding competes with duplex formation due to intermolecular phenol·phosphine oxide base-pairing interactions.