Photoinduced Ring‐Opening Polymerization of <i>N</i> ‐Carboxyanhydrides for the Preparation of Cross‐Linked Polypeptide Gels

Abstract Using light to activate chemical reactions is a powerful approach that allows spatiotemporal control over physicochemical transformations, commonly used in the polymerization and solidification of reactive liquids. Here, we employ a photochemical approach for ring‐opening polymerization (ROP) of α‐amino acid N ‐carboxyanhydride (NCA) monomers to prepare covalently cross‐linked synthetic polypeptide gels using light. We apply 2‐nitrobenzyl carbamate as a photocaged amine (base), where the switch in its activity after illumination is a key factor in controlling ROP. The released dibutylamine, as a basic species, can deprotonate the NCA and thereby initiate polymerization. We investigate the effects of 2‐nitrobenzyl dibutyl carbamate on γ‐benzyl‐ l ‐glutamate NCA polymerization and apply this approach to prepare covalently cross‐linked polypeptide gels. We demonstrate excellent 2D spatiotemporal control over gelation, further enhanced by the use of an acid inhibitor that prevents overcuring caused by diffusion of active species from the illuminated region. The development of photoinduced polymerization and cross‐linking of NCAs offers significant advantages in polypeptide synthesis and holds great potential for further applications in additive manufacturing.