The carboxamide group is generally inert, except under harsh conditions or in the presence of highly evolved enzymes. We have identified several metal complexes that efficiently catalyze transamidation reactions of amine/amide mixtures (eq 1) under moderate conditions. This unprecedented reactivity represents an important step toward our long-term goal of using dynamic covalent chemistry to generate new amide-based polymers and materials with interesting structures and functions. In addition, we have shown that our transamidation catalyst is effective for the polymerization of β-lactams.

Our immediate future goals include discovering metal complexes that catalyze amide metathesis between or among amide reactants (eq 2) and then optimizing those catalysts. These goals will be furthered through the synergy of synthetic, mechanistic, and computational studies. The development of highly active catalysts will allow amide exchange reactions to be conducted under thermodynamic control, thereby extending the principles of dynamic covalent chemistry to amides. Under these conditions, non-covalent interactions with internal or external templates can be used to direct the formation of materials not accessible by any other methods.

Materials prepared using this strategy have enormous potential for practical application. Synthetic polyamides like Nylon and Kevlar and natural ones such has proteins, wool, and silk are already of enormous value to our society. Amide exchange catalysts will enable the synthesis of a great many more types of synthetic polyamides. In addition, we will begin to bridge the gap between proteins and synthetic polyamides by using template-directed polymerizations to direct residue order within the polymaide backbone. Selected examples of potential applications of these new synthetic polyamides include antimicrobial agents, gene delivery vectors, and lung surfactants.