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.

Precision synthesis of polymers has been a hot topic in recent years. While this is notoriously difficult to address for polymers with a CAC backbone, Merrifield has discovered a way many decades ago for polypeptides. Using a similar approach, N-substituted polypeptides, so-called polypeptoids have been synthesized and studied for about 20 years. In contrast, the living ring-opening polymerization (ROP) of N-substituted N-carboxyanhydrides was among the first living polymerizations to be discovered. More recently, a surge in new synthetic approaches led to the efficient synthesis of cyclic or linear multiblock copolypeptoids. Thus, polypeptoids can be synthesized either by solid phase synthesis to yield complex and exactly defined oligo-and small polymers or by ROP of appropriately N-substituted N-carboxyanhydrides (NNCA) to give linear, cyclic, or star-like polymers. Together with an excellent biocompatibility, this polymer family may have a bright future ahead as biomaterials.

Poly(α-peptoid)s (N-substituted polyglycines) are interesting peptidomimetic biomaterials that have been discussed for many applications. Poly(β-peptoid)s (N-substituted poly-β-alanines), although equally intriguing, have received much less attention. Here we present results that suggest that while N-substituted β-alanine N-carboxyanhydrides can undergo a living nucleophilic ring-opening polymerization, the solubility of poly(β-peptoid)s can be very poor, which contributes to the limited accessibility using other synthetic approaches. The living character of the polymerization was utilized for the preparation of the first polymerized amphiphilic block copoly-β-peptoid. Our results may open a new route towards highly defined functional poly(β-peptoid)s which could represent biomaterials.