NMR spectroscopic investigation on polymerization mechanisms of amino acid NCAS

Abstract

Polymerizations of α‐aminoacid N‐carboxyanhydrides (α‐NCAs) can be initiated by nucleophilic or basic reagents. Depending on the nature of the reagent, nucleophilic attack at the carbonyl group C‐5 or deprotonation of the N‐H group may be the first reaction step. 1H NMR spectroscopy is best suited to detect incorporation of initiator fragments. In the case of primary aliphatic amines quantitative endgroup analyses may even allow the calculation of the average degree of polymerization (DP). In the case of base‐initiated polymerization the formation of N‐acyl‐NCA endgroups or the incorporation of the basic initiator is detectable. Furthermore, the role of electrophilic co‐catalysts, such as isocyanates or N‐acyl‐NCAs, can be elucidated. 13C‐ and 15N NMR spectroscopy are better suited than 1H NMR spectroscopy for stereosequence analyses of poly(D,L‐amino acid)s. The results of both methods agree in that primary amine‐initiated polymerizations of D,L‐NCAs yield nearly random stereosequences. Trialkylamine initiated polymerizations of α‐helix forming D,L‐NCAs favour the formation of isotactic blocks, whereas in the case of non‐helicogenic NCAs (e.g. D,L‐Val‐NCA) syndiotactic blocks are preferentially formed. 15N NMR spectroscopy also enables the sequence analysis of binary copolypeptides, and in favourable cases even ternary copolypeptides can be analyzed. 13C NMR crosspolarization/magic angle spinning (CP/MAS) spectroscopy of solid polypeptides enables the qualitative and quantitative determination of their secondary structure. Such investigations revealed that primary amine and tertiary amine‐initiated polymerizations may yield different ratios of crystallites built up by β‐sheets or α‐helices and thereby bimodal molecular weight distributions (MWDs).

Fast Catalyst-Free Synthesis of Stereoselective Polypeptides via Hierarchical Chiral Assembly

“…Both k values of 0.161 and 0.056 min –1 in racemic ZDLL-NCA polymerization using a probe ultrasonic processor and in an ultrasonic cleaning bath with constant stirring were slightly lower than that of enantiopure ZLL-NCA polymerization (0.198 and 0.082 min –1 , respectively), suggesting potential differences in kinetics (Figures g and S26–S29). The stereoselectivity of the polymer during the polymerization process was further monitored using homonuclear-decoupled 1 H NMR, denoted as an isotactic sequence forming probability P m . − In the case of PEG 113 - b -PZDLL 34 , P m exhibited a slight variation from 0.76 to 0.71 at different polymerization times (Figures i,j). The P m values were further confirmed by 13 C NMR spectra (Table S3).…”