Peptide Bond Formation In Nano-Reactors

A frequent reaction used in organic synthesis is amide bond formation also known as peptide bonds in proteins. Amide bond formation is commonly achieved through the combination of an amine and an activated carboxylic acid. Reports of amide bond formation through the direct coupling of carboxylic acids and amines are non-existent. The favored reaction between the amine and carboxylic acid is an equilibrium reaction. Water is produced in the forward condensation reaction and acts to hydrolyze the new bond in the reverse reaction. Recently, we have developed a method for the direct coupling of the amine and carboxylic acid using nano-reactors. The nano-reactors have three characteristics that allows them to facilitate direct amide bond coupling: (1) Nano-reactors absorb organic molecules into central cavities. (2) Upon absorption, the nano-reactor swells 3 times its dry volume. (3) The nano-reactor is hydrophobic, water does not enter the central cavity and water synthesized in the cavity migrates out. The produced water is expelled and drives the reaction forward. When applied to the synthesis of proteins, which has challenged chemists for over a century, trial syntheses conducted using nano-reactors and amino acids occur with high efficiency and yield. These advancements have multiple applications.