Sarcosine NCAs, polymerization

Fig. 7. Conversion-time curves for polymerization of NCA s (0.224 mole l l) with amines (0.015 mole l-1) at 25 C in iV.iV-dimethylformamide. O y-Ethyl-L-glutamate NCA-di-isopropylamme A y-Ethyl-L-glutamate NCA-n-hexyl-amine Q Sarcosine NCA-di-isopropylaraine Sarcosine NCA-n-hexylamine. (Reprinted from paper by C, H. Bamford, and H. Block Polyamino Acids, Polypeptides and Proteins, p, 65, Wisconsin University Press 1962 (Fig. 7)3...

It has been established that the polymerization of sarcosine NCA can be initiated by tertiary bases [18] and chloride ion [37] when (XI) is... 

Fig. 1. Conversion—time curves for the polymerization of 7-ethyI-L-glutamate NCA (0.2 mole 1 ) in Af,Al-dimethylformamide by pyridine and homologues (2.0 mole 1" ) at 25°C. o 2,6-lutidine, a-picoline, A pyridine. The broken curve shows a comparative experiment with sarcosine NCA (0.2 mole 1" ) and 2,6-lutidine (2.0 mole 1" ). Bamford and Block [ 19 ].

Fig. 2. Conversion—time curves for polymerization of NCAs (0.224 mole 1 ) initiated by amines at 25°C in i i,AT-dimethylformamide solution, o 7-ethyl-L-glutamate NCA/di-isopropylamine, sarcosine NCA/n-hexylamine, 7-ethyl-L-glutamate NCA/n-hexylamine, Dsareosine NCA/di-isopropylamine. Bamford and Block [22],...

The presence of a substituent in the 3-position of the NCA precludes equilibrium (6) and hence prevents the occurrence of reaction (18). It follows that, on the basis of the mechanisms described above, such NCA s should not polymerize unless a protic base (for example a primary or secondary amine) or other source of protons (for example, 3-methyl hydantoin) is present. If it could be established that polymerization does proceed with an aprotic base in aprotic media then some other mechanism of polymerization must be operative. This matter has been of central importance in discussions of various mechanisms of polymerization which have been advanced (Section 3). Experimentelly, it is not easy to obtain definitive evidence because of the high sensitivity of NCA s to protonic impurities (such as water and alcohols) in the presence of bases. It has been shown [18, 19, 38a] that proline NCA (X) and sarcosine NCA (I Ri = R2 = H, R3 = CH3) do not polymerize in the presence of tertiary bases under strictly aprotic conditions. With alkoxides, realization of such conditions is difficult, but it would appear that, at least with proline NCA, such strong bases can bring about ionization of the methine hydrogen and hence initiate polymerization as shown in (26). Evidence for this mechanism is provided by the observation that while sodium methoxide enriched... 

Fig. 4. Dependence of first-order rate coefficient for the polymerization of sarcosine NCA in AT,Al-dimethylformamide on concentration of preformed polymer [I]o in the absence and presence of hydrocinnamic acid. Zero CO2 pressure and 25°C. Hydrocinnamic acid concentrations Zero, o 2.5 x 10 mole 1" 2.5 x 10 ...

Fig. 7. Polymerization of sarcosine NCA in benzene at 25°C initiated by n-hexyl- ine. [NCAlo = 0.100 mole I, [n-hexylamineJo = 10 mole 1. Axis on right P = mean size of growing polymer chains. The arrow marks the point at which separation of polymer begins. Ballard and Bamford [70].

Despite the drawbacks of this method, it has been used to prepare a tremendous number of polypeptide hybrid block copolymers (Table 1), and when carefully executed provides reasonably well-defined samples. Synthetic polymer domains have been prepared by addition polymerization of conventional vinyl monomers, such as styrene and butadiene, as well as by ringopening polymerization in the cases of ethylene oxide and e-caprolactone. The generality of this approach allows NCA polymerization off of virtually any primary amine functionality, which was exploited in the preparation of star block copolymers by polymerization of sarcosine NCA from an amine-terminated trimethyleneimine dendritic core [37]. In most examples, the polypeptide domain was based on derivatives of either lysine or glutamate, since these form a-helical polypeptides with good solubility characteristics. These residues are also desirable since, when deprotected, they give polypep-... 

Primary amine-catalyzed polymerization of NCAs in various solvents revealed that certain polar solvents themselves act as catalysts [3]. Characteristic for the catalytically active solvents is a relatively high nucleophihcity [4] (see left column in Table 15.1). This observation and the formation of cyclic polypeptides from the N-substituted sarcosine-NCA evidenced that a zwitterionic polymerization mechanism was catalyzed, which involves ROP and condensation steps (see Formula 15.2). Pyridine is known for many decades to activate carboxylic anhy-drdies by charge separation, i. e., formation of carboxylate anions plus N-acyl pyridinium ions Therefore, it is obvious that pyridine catalyzes the same zwitterionic mechanism as the nucleophilic polar solvents [5]. In the case of N-un-substitued NCAs the initiation step will be again a charge separation, but instead of... 

Ring-opening copolymerization was simultaneously investigated with homopolymerization of N-carboxy-a-amino acid anhydrides, NCAs, by Bamford at al Polymerization of a mixture of NCAs of y-ethyl-L-glutamate and sarcosine ... 

Fig. 21. Polymerization of DL-phenylalanine NCA initiated by sarcosine dimethylamide (o) polysarcosine...

According to the mechanisms outlined in Sections 1 and 2, substitution in the 3-position should preclude polymerization by the ionization route. This is indeed found to be so for example, sarcosine and proline NCAs ((IX), (X), respectively) cannot be polymerized by tertiary amines when... 

Polymerization of DL-phenylalanine NCA. Initiation by poly-L-proline and block copolymers of L-proline and sarcosine. (Nitrobenzene solution at 25°C. [NCAJo =0.1 mole r )... 

Another type of polypeptide-containing block copolymer, amphiliphilic rod-coil diblock copolymers such as poly (/V-triflu-oroacetyl-L-lysine)-/>-sarcosine) (Kt - Sa), were also synthesized and characterized by Gallot and coworkers [47]. The hydrophobic rod block poly(A-trifluoroacetyl-L-ly-sine) (Kt) was prepared by polymerization of Kt-NCA using A-hexylamine as the initiator. After fractionation using DMF (good solvent)/water (nonsolvent), the narrowly dispersed polymer (Kt) was then used as macroinitiator to initiate polymerization of the second monomer (Sa-NCA) to afford the hydrophilic block. Final elimination of Kt and Sa homopolymers were performed by precipitation with acetone and water respectively. The synthesis of Kt-Sa diblock copolymer is shown in Scheme 3. 

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