Divergent Synthesis of Biocompatible Nearly Monodisperse Multi‐Functional Poly(ethylene glycol) Periodic Copolymers

Abstract

Functional nearly monodisperse (Ð < 1.1) poly(ethylene glycol) (PEG) copolymers, containing precise functional groups both in the backbone and chain end, are challenging to prepare. Herein, a divergent synthetic approach is reported to prepare a library of functional PEG periodic copolymers with very narrow dispersity (Ð < 1.1). In the first step, acrylate end functional (at one of the chain end) PEG copolymers (M n = 3000-14 000 Da) (PEG-1) are synthesized via the reaction between commercially available PEG diacrylate oligomers (M n = 575 Da) and primary amines. Besides the acrylate end group, PEG-1 contains periodic alkyl chains and amino-ester functionalities in the backbone which are introduced by respective amines. The acrylate end group can react with different primary and secondary amines (such as tryptamine, diethanolamine) to synthesize different end functional polymers via end group modifications (PEG-2). Further, the acrylate end functional polymers react with piperazine and ethanol-amino piperazine to form the higher molecular weight linear (PEG-3) and star polymers (PEG-4) respectively via macromolecular coupling. All the polymers are characterized by NMR, IR, and SEC. Further purity of the end functional polymers is confirmed via DOSY NMR analysis. The different amphiphilic functional polymers self-assemble in water to form stable micelles (D h < 50 nm), where the size of the micelles increases with increasing molecular weight of the polymers. The micelles can be used for drug encapsulation and release. MTT assay is performed to study the general cytotoxicity of the functional PEGs using L929 cells. The results indicate very good biocompatibility of the current polymers for further biomedical applications.

Hydrophobic PEGylation of Chitosan: A Graft Copolymer Approach toward Developing Nontoxic Antimicrobial Chitosan

“…As per the screening, the optimum reaction condition for a quantitative reaction between chitosan and methyl acrylate is established as follows: the reaction using water as a solvent in the presence of 1,4-diazabicyclo[2.2.2]­octane (DABCO) as a base confirms >95% conversion. As a grafting chain, acrylate end functional hydrophobic PEG copolymers (such as octyl-PEG [OPEG] and butyl-PEG [BPEG]) were prepared following a similar synthetic protocol as earlier reported by our group . The 1 H NMR reveals the molecular structure of the hydrophobic PEGs and the presence of end groups (peaks between 5 and 6.5 ppm) (Figure S2 and S3).…”

“…[OPEG] and butyl-PEG [BPEG]) were prepared following a similar synthetic protocol as earlier reported by our group. 31 The 1 H NMR reveals the molecular structure of the hydrophobic PEGs and the presence of end groups (peaks between 5 and 6.5 ppm) (Figure S2 and S3). The molecular weight, as calculated via both 1 H NMR and SEC (Figure S4) reveals comparable molecular weight (Table S4).…”

“…Linear acrylate end functional PEG copolymers were prepared by addition reaction between PEG-diacrylate and primary amine in a 1:1 ratio of −CH 2 /−NH, in water/DMF (2:1) mixture following a similar synthetic protocol reported in literature. 31 In short, PEG-diacrylate (2 g, 3.478 mmol) was reacted with butylamine (0.346 mL, 3.478 mmol) in water and a DMF mixture (12.66 mL: 7.34 mL). The reaction mixture was kept under continuous magnetic stirring for 72 h at room temperature.…”

Solution Self‐Assembly of Branched Macromolecules Obtained via Iterative OPE Synthesis and the Passerini Three‐Component Reaction

“…It can be used, for example, as a method to determine the purity of a compound or to assign NMR signals to compounds in a complex mixture. [ 52–56 ] Moreover, it was shown to be a suitable tool for the investigation of self‐assembly to supramolecular structures. [ 57–61 ]…”

“…It can be used, for example, as a method to determine the purity of a compound or to assign NMR signals to compounds in a complex mixture. [52][53][54][55][56] Moreover, it was shown to be a suitable tool for the investigation of self-assembly to supramolecular structures. [57][58][59][60][61] In this work, we present the divergent synthesis of dendrons using uniform OPEs of different lengths as focal moieties by applying the P-3CR as a branching reaction, using the OPEs as carboxylic acid component (Figure 1).…”