Polypeptoids from N-Substituted Glycine N-Carboxyanhydrides: Hydrophilic, Hydrophobic, and Amphiphilic Polymers with Poisson Distribution

Abstract

Preparation of defined and functional polymers has been one of the hottest topics in polymer science and drug delivery in the recent decade. Also, research on (bio)degradable polymers gains more and more interest, in particular at the interface of these two disciplines. However, in the majority of cases, combination of definition, functionality and degradability, is problematic. Here we present the preparation and characterization (MALDI–ToF MS, NMR, GPC) of nonionic hydrophilic, hydrophobic, and amphiphilic N-substituted polyglycines (polypeptoids), which are expected to be main-chain degradable and are able to disperse a hydrophobic model compound in aqueous media. Polymerization kinetics suggest that the polymerization is well controlled with strictly linear pseudo first-order kinetic plots to high monomer consumption. Moreover, molar mass distributions of products are Poisson-type and molar mass can be controlled by the monomer to initiator ratio. The presented polymer platform is nonionic, backbone degradable, and synthetically highly flexible and may therefore be valuable for a broad range of applications, in particular as a biomaterial.

Thermal Properties of Aliphatic Polypeptoids

“…The living character of the nucleophilic ring-opening polymerization (NuLROP) of NNCAs other than Sar-NCA was shown by Luxenhofer and co-workers [22]. In particular, the successful preparation of a pentablock quinquiespolymer highlighted the unique character of the NNCA NuLROP [23].…”

Polypeptoid polymers: Synthesis, characterization, and properties

“…[15][16][17][18][19][20] The relative cell viability was found to be dependent on the polymer composition and concentration. It was found that relative cell viability decreases with increasing polymer concentration for all polymers (Figure 13).…”

“…In recent years, the substrate scope for polymerization studies was further expanded to include a variety of R-NCA monomers bearing various N-substituents ( Figure 2). [5,6,[15][16][17][18][19][20][21][22] Luxenhofer et al demonstrated that the polymerizations of Me-NCAs using benzyl amine initiators were shown to proceed in a controlled manner without chain transfer or termination events, producing polysarcosines with narrow Poisson distribution (PDI < 1.1-1.3) and M n s that can be controlled by the initial monomer to initiator feed ratios. [56] The molecular distribution remains narrow (PDI 5 1.01-1.07) even after ten sequential polymerizations of Me-NCA monomers (DP < 100), attesting to the robustness of the living polymerization and suggesting the potential uses of the methods towards the synthesis of well-defined block copolypeptoids via sequential monomer addition.…”

“…. [16,18,[33][34][35][36][37] N-substituted glycine precursors can also react directly with phosgene to yield R-NCA monomers. [38,39] The former methods are more popular than the latter due to the avoidance of toxic phosgene as well as the relative ease of purification to afford high purity R-NCA monomers.…”

“…The polypeptoid backbone containing tertiary amide linkages is highly polar and hydrophilic. The physicochemical properties of polypeptoids can be tailored by the N-substituent structures, enabling control over the hydrophilicity and lipophilicity balance (HLB), charge characteristics, [13,14] backbone conformation, [1][2][3][4][5][6][7][8][9][10][11][12] solubility, [15][16][17][18][19][20] thermal and crystallization properties of the polypeptoids. [21][22][23][24] Without extensive hydrogen bonding, polypeptoids are thermally processable similar to conventional thermoplastics, [20][21][22][23][24] whereas polypeptides undergo thermal degradation before they can be melt-processed due to the extensive hydrogen bonding interactions.…”