Crystallization of polypeptides in the course of polymerization, III. Further studies on the growth mechanisms of poly(<scp>L</scp>‐alanine) crystals

Abstract

Abstract In order to establish the mechanism proposed previously for the formation of the extended chain crystals during the heterogeneous polymerization of the LEUCHS anhydride 4‐methyl‐2,5‐oxazolidinedione ( L ‐alanine NCA) in acetonitrile, oligo‐ L ‐alanines were prepared by purely organic chemical methods. Their solubility, conformations in various solvents and those in the crystallized states were studied and compared with those in the crystals formed directly in the course of the heterogeneous polymerization. It was found that the growing chain molecules became insoluble in acetonitrile and crystallized into the β‐conformation when they attained a \documentclass{article}\pagestyle{empty}\begin{document}$ \overline {\rm{DP}} $\end{document} of 3. As the growing chains in the course of the heterogeneous polymerization attained \documentclass{article}\pagestyle{empty}\begin{document}$\overline {\rm{DP}}$\end{document} of 10–13 ( i.e. 7–10 from the basal plane of the original skeleton crystals) by further polymerization, they crystallized into the α‐helical conformation. Due to the topochemical nature of the chain growth, this critical length for the formation of the α‐helix is shorter than that found in solution for the corresponding oligomers already synthesized ( i.e. , \documentclass{article}\pagestyle{empty}\begin{document}$\overline {\rm{DP}}$\end{document} &gt; 10). It was also shown that the crystalline nuclei with the β‐conformation, formed in the very early stages of the polymerization, remain throughout the polymerization. In order to examine the rôle of acetonitrile in this particular type of polymerization, the polymerization of L ‐alanine NCA was studied also in dioxane and propionitrile. The chains grown from the basal plane of the skeleton crystals with the β‐conformation remain in some state like random coils until they attain the critical length for the formation of the α‐helix. This critical length seems to depend on the solvation power (including the steric factor) of the solvent used. In the case of acetonitrile, the dipole‐dipole interaction with polypeptides may play an important rǒle in this type of solvation.