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

Abstract

Peptidomimetic polymers containing hydrophobic amino acids and non-peptidic 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.