Investigation of the solid-state polymerization of N-carboxy α-amino acid anhydrides with reference to their crystal structures

Abstract

Solid-state polymerizations of N-carboxy anhydrides (NCAs) of α-amino acids ( l-leucine, l-alanine, γ-benzyl- l-glutamate and glycine) were carried out using butylamine as initiator in hexane at 20–50°C. The results were compared with those for polymerization in acetonitrile solution. l-Leucine NCA was the most reactive among the NCAs examined, and formed high-molecular-weight polypeptide in the solid state. In contrast, l-alanine NCA polymerized faster than any other NCAs examined and formed high-molecular-weight polypeptide in acetonitrile compared to the solid-state polymerization. X-ray analysis, electron microscopy and infra-red spectroscopy revealed that l-leucine NCA polymerized to form α-helical polypeptide predominantly along the c axis in the crystal, while the α-helical polymer grows in random directions in the crystal of L-alanine NCA. Although γ-benzyl- l-glutamate NCA polymerized a little slower in the solid state than in acetonitrile, its polymerization reached 100% conversion and formed polypeptide with higher molecular weight than the value expected from the molar ratio of the monomer to the initiator. Glycine NCA polymerized very slowly in the solid state. These differences could be explained by their crystal structures. Favourable features for solid-state polymerization were found in the crystal of l-leucine NCA : five-membered rings of the NCA make a layer sandwiched by two hydrophobic side-chain layers and the NCA molecules polymerize to form the a-helical polypeptide in a layer without any interference from the other layers. On the other hand, such a layer structure was not seen in the crystal structure of l-alanine NCA. In the crystal of γ-benzyl- l-glutamate NCA, the layer structure similar to l-leucine NCA was observed and this seemed to activate the polymerization of the NCA, while the long side chains were considered to make molecular rotation difficult to some extent in the crystal. Glycine NCA seemed to be stable because of the dimer structure in the crystal.