α,ω‐Functionalized Poly(2‐Oxazoline)s Bearing Hydroxyl and Amino Functions

Abstract

Novel α,ω‐functionalized amphiphilic lipopolymers are prepared that are composed of a proximal lipid moiety and a hydrophilic poly(2‐oxazoline)‐based (POx) polymer chain. The synthesis begins from bifunctional lipoinitiators, which are asymmetrically protected as tert.butyldiphenylsilyl (TBDPS) ethers, followed by cationic living ring‐opening polymerization of 2‐oxazolines in a one‐pot multistep reaction. This results in polymers with defined terminal end groups and narrow molar mass distributions. All protective groups involved can be readily cleaved in a single step reaction keeping the structure of the polymer intact, giving access to (lipo)polymers with a variety of defined identical or chemical orthogonal α,ω‐functionalities. The synthetic strategy is a versatile tool for the preparation of defined polymer–drug or polymer–protein conjugates or asymmetric functionalized model lipid membranes for the quantitative study of membrane‐associated phenomena such as transmembrane transport and cell adhesion/recognition.

Poly(2‐oxazoline)s as Polymer Therapeutics

“…Functional initiators have been used to realize among others, alkyne [13] , amine, [14] hydroxyl [15] or carboxylic acid [16] bearing POx (with protection groups where needed) to allow further functionalization (Figure 3a). In a number of other accounts functionality by structure was also introduced via the initiators such as lipids, [17], [18] porphyrins, [19] or saccharides.…”

“…[23], [86] Mono- and difunctional initiators yield linear symmetric or asymmetric telechelic polymers. [15], [87] while higher plurifunctional initiators give tri-, tetra- etc. arm star polymers, [88] , bow-tie multi-arm stars [35] and ultimately, macroinitiators result in comb copolymers or at high grafting densities in molecular brushes (Figure 5).…”

Stealth Polymeric Vesicles via Metal-Free Click Coupling

“…Alternatively, an approach using 2 M aqueous HCl resulted in quantitative Boc cleavage to provide the secondary amine. 16 Following deprotonation of the polymer chain with potassium carbonate, PMOXA-pip (2) was provided with the desired piperazine end-group.…”

Biocompatibility and Immunocompatibility Assessment of Poly(2-Oxazolines)

“…Lipid-tehtered poly(2-methyl-2-oxazoline) lipopolymer chains can be used as Langmuir monolayers at the air-water interface [51]. Recently, novel alpha,omegafunctionalized amphiphilic lipopolymers based on a proximal lipid moiety and hydrophilic poly(2-oxazoline) were used in asymmetric functionalized model lipid membranes for transmembrane transport and cell adhesion/recognition [52]. Amphiphilic co-networks composed of more hydrophilic poly(2-hydroxyethyl acrylate) and more hydrophobic, telechelic poly(2-ethyl-2-oxazoline) segments were prepared as free-standing membranes for entrapment of an enzyme molecule [53].…”