Mechanistic Study of α-Amino Acid N-Carboxyanhydride (NCA) Polymerization by Capillary Electrophoresis

Polymerizations of Nε‐trifluoroacetyl‐L‐lysine N‐carboxyanhydride initiated by hexylamine were performed in N,N‐dimethylformamide with different monomer to initiator ratios and at different temperatures. Poly(Nε‐trifluoroacetyl‐L‐lysine) samples were characterized by size exclusion chromatography coupled with multi‐angle laser light detection (SEC‐MALLS) and capillary electrophoresis (CE). If SEC‐MALLS analysis emphasizes the double distribution in molecular weight, nonaqueous CE (NACE) brings additional quantitative information on the oligomeric distribution and on the distribution according to polymer functionality (end‐groups). At room temperature, two termination reactions were clearly identified for these polymerizations. The suppression of these side reactions is reported upon decreasing the reaction temperature to 0 °C. A strong reduction of the bimodal aspect of the molecular weight distribution was obtained with the addition of urea to the polymerization medium. The possibility of a living and controlled polymerization at 0 °C with urea was demonstrated and illustrated by the synthesis of two block copolypeptides.