Topochemical Polymerization of Retro‐Isomeric Peptides for Tuning the Polymer Structure and Properties

Peptidomimetic polymers containing hydrophobic amino acids and nonpeptidic linkages are interesting for various applications, particularly hydrophobic coatings. We synthesized two retro-isomeric peptide monomers decorated with azide and alkyne, viz. N₃-L-Phe-L-Val-NHCH₂CCH (M1) and its retro-isomer N₃-L-Val-L-Phe-NHCH₂CCH (M2), for topochemical azide-alkyne cycloaddition (TAAC) polymerization. On heating the crystals at 100 °C, both monomers underwent TAAC polymerization, yielding isomeric "difficult peptide" polymer mimics. The monomers showed stark differences in reactivity and regiochemistry of the product formed. Monomer M1 yielded polymer P1 having a 1:1 ratio of 1,4- and 1,5-triazolyl-linkages, and monomer M2 reacted regiospecifically, giving 1,4-triazolyl-linked polymer P2. We investigated the hydrophobicity of these isomeric polymers by measuring water contact angles (WCA) of surfaces coated with these polymers; P1 and P2 showed WCA of 120° and 132°, respectively. Our study demonstrates that sequence reversal is a novel approach for accessing structurally and functionally different polymers via topochemical polymerization.