Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone-Backbone Interaction Motifs

Abstract

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions.

Keywords: biomimetics; macromolecules; sequence-defined polymers; simulations; solid-phase synthesis.

Scheme 1

Triazine‐based polymers.

Scheme 2

Submonomer solid‐phase synthesis of a triazine‐based polymer.

Figure 1

HPLC chromatogram of crude and pure TZP 3.

Figure 2

High‐resolution mass spectrum and isotopic pattern of TZP 3. The expanded spectrum shows the adduct [M+H]⁺.

Figure 3

¹H NMR spectra (500 MHz) of TZPs 3 (upper) and 4 (bottom) in deuterated methanol.

Figure 4

Tandem MS spectra of the [M+H]⁺ adduct of TZPs 3 (upper) and 4 (bottom). Fragments from breaking triazine rings(T) are indicated by ring number and left(L) or right(R) fragments. See the Supporting Information for details.

Figure 5

MD simulations of a) two tetramers and b) two trimers interacting by hydrogen bonding and pi–pi interactions. Side chains are S‐ethyl, and nonpolar hydrogen atoms are not shown.

Figure 6

Backbone–backbone hydrogen‐bonding motifs found in molecular dynamics simulations of triazine‐based polymers. Paired hydrogen bonds in DNA and peptide beta sheets are shown for comparison.