Copolypeptides conditions

Hadjichristidis et al. applied a high-vacuum technique for the primary amine-initiated NCA polymerization. Under these conditions they were able to synthesize homopolypeptides and block copolypeptides with controlled molar-mass characteristics. In their efforts, Giani and co-workers studied the polymerization of s-trifluoroacetyl-L-lysine NCA in DMF with n-hexylamine as initiator as a function of temperature. They found that, for polymerizations conducted at 0 °C, almost all of the chains (99%) had living... 

The most likely pathways of NCA polymerization are the amine and activated monomer (AM) mechanisms [11, 12]. The amine mechanism is a nucleophilic ring-opening chain growth process where the polymer would grow linearly with monomer conversion if side reactions were absent Eq. (2). On the other hand, the AM mechanism is initiated by deprotonation of an NCA, which then becomes the nucleophile that initiates chain growth Eq. (3). It is important to note that a polymerization can switch back and forth between the amine and AM mechanisms many times a propagation step for one mechanism is a side reaction for the other, and vice versa. It is because of these side reactions that block copolypeptides and hybrid block copolymers prepared firom NCAs using amine initiators under conventional conditions (i.e., 20°C, 1 atm) have structures different than predicted by monomer feed compositions and most probably have considerable homopolymer contamination. These side reactions also prevent control of chain-end functionality, which is desirable for many applications. 

The use of amine hydrochloride salts as initiators for controlled NCA polymerizations shows tremendous promise. The concept of fast, reversible deactivation of a reactive species to obtain controlled polymerization is a proven concept in polymer chemistry, and this system can be compared to the persistent radical effect employed in all controlled radical polymerization strategies [61]. Like those systems, success of this method requires a carefully controlled matching of the polymer chain propagation rate constant, the amine/amine hydrochloride equilibrium constant, and the forward and reverse exchange rate constants between amine and amine hydrochloride salt. This means that it is likely that reaction conditions (e.g., temperature, halide counterion, solvent) will need to be optimized to obtain controlled polymerization for each different NCA monomer, as is the case for most vinyl monomers in controlled radical polymerizations. Within these constraints, it is possible that controlled NCA homopolymerizations utilizing simple amine hydrochloride initiators can be obtained yet this method may not be advantageous for preparation of block copolypeptides due to the need for monomer-specific optimization. 

The majority of amine-initiated block copolypeptides were often subjected to only limited characterization (e.g., amino acid compositional analysis) and, as such, their structures and the presence of homopolymer contaminants were not conclusively determined. Some copolymers, which had been subjected to chromatography, showed polymodal molecular weight distributions containing substantial high and low molecular weight fractions [15]. The compositions of these copolymers were found to be different from the initial monomer feed compositions and varied widely for different molecular weight fractions. It appears that most, if not all, block copolypeptides prepared using amine initiators under conventional conditions have structures different to those than predicted by monomer feed compositions and probably have considerable homopolymer contamination due to the side reactions described above. 

Table 1.1 Silica morphology for each copolypeptide at different synthesis conditions.

Jan, J.-S. and Shantz, D.F. (2007) Biomimetic silica formation effect of block copolypeptide chemistry and solution conditions on silica nanostructure. Advanced Materials, 19, 2951-6. 

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