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

Abstract

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.magnified image

Homo and Block Copolymers of Poly(β‐benzyl‐L‐aspartate)s and Poly(γ‐benzyl‐L‐glutamate)s of Different Architectures

“…The PBA‐Hs that we obtained from the HEX‐initiated Asp NCA polymerizations at room temperature had lower molar‐mass averages than predicted from the [M]:[I] ratios (50, 100, 200), but the results are in agreement with the trend of $\overline {M} _{{\rm n}} $ increase with the increasing [M]:[I] ratios (Table 1). Longer times were avoided to minimize the chain‐terminating reactions 19, 20, 22. By doubling the [M]:[I] ratio, a practically doubled molar‐mass average was observed.…”

“…Control over the NCA polymerizations can only be achieved by keeping the polymer NH 2 end‐group as the only initiating species. Using capillary electrophoresis it was demonstrated by Vayaboury et al19, 20 that by lowering the reaction temperature to 0 °C, NH 2 end‐groups remain present for 99% of the polypeptide chains. It was suggested that the reactions of end‐groups with N,N ‐dimethylformamide (DMF) forming formamide‐terminated dead polypeptide chains are more pronounced at higher reaction temperatures.…”

Controlled metal‐free polymerization toward well‐defined thermoresponsive polypeptides by polymerization at low temperature

“…[42][43][44][45][46] Alternatively, the polymerization of MES-L-Glu-NCA at 0 8C was attempted. We reasoned the side reactions were considerably slower at this temperature.…”

Block Copolypeptides Prepared by N‐Carboxyanhydride Ring‐Opening Polymerization

“…However, although the ammonium halide mechanism is reported for the successful synthesis of hybrid block copolymers, no report has been found for the synthesis of block copolypeptides 36. Other methods exploit high vacuum and/or low temperature to optimize the conditions needed for a living polymerization 37, 38. During NCA polymerization under high vacuum, the carbamic groups and CO 2 are removed at a faster rate compared to when the reaction proceeds under atmospheric pressure.…”