Synthesis And Characterization Of Dendrimer-like Polyethylene Oxide

Polyethylene oxide(PEO) with unique properties such as nontoxicity, chemical stability, solubility in both organic and inorganic solution, low immunogenicity, was known as gold carrier of drug delivery, is one of the most popular biocompatible polymers. As dendrimer polymer, the dendrimer-like polymer has a better coverage than star or hyperbranched polymer due to the special dendritic branched structure, refer as dense outer and loose inside core. Dendrimer-like polymers were often used to construct unimolecule micelles to improve their stability and encapsulation efficiency of the drug. Cu-catalyzed azide/alkyne click reaction was one of the most popular click reactions applied in synthesis of functional materials due to its high efficiency and compatibility with other functional groups. Traditional synthesis of dendrimer-like polymer includes arm-first which can get high molecular polymer but the structure is hardly to remain when the generation is high and core-first which can get perfect structure but it is hard to obtain high generation because of the increased steric hindrance.In this paper, we aimed at the synthesis of dendrimer-like polyethylene oxide with perfect structure via the anionic ring-opening polymerization(AROP) combined with click chemistry. Dendrimer-like polymer was synthesized via arm-first or core-first. The products were characterized by Nuclear Magnetic Resonance(NMR), Fourier Transform Infrared Spectroscopy (FTIR), Gel Permeation Chromatography(GPC) and Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The details are as follows:1. Synthesis of linear PEO, star PEO and its derivatization reaction A linear polyethylene oxide(linear PEO-ketal) was firstly prepared based on the anionic ring-opening polymerization of ethylene oxide from a ketal which was deprotonated using diphenylmethylpotassium(DPMK) and tetrahydrofuran as the solvent. The alkyne group of linear alkyne-PEO-ketal was introduced via the reaction between the linear PEO-ketal and 2-propargyl bromide. The two hydroxyl groups in linear alkyne-PEO-2OH were transferred from the ketal under acidic tetrahydrofuran. The linear polyethylene oxide with alkynyl and bromine as terminal groups(linear alkyne-PEO-2Br) was synthesized via esterification reaction with 2-bromo-propionate, this product could be as the arm of dendrimer-like polymer. A three-arm polyethylene oxide(star PEO-3OH) was synthysized based on the AROP of EO from TME deprotonated by DPMK and dimethyl sulfoxide as the solvent. A star polymer with bromine as terminal group(star PEO-3Br) was synthesized via sterification reaction with 2-bromo-propionate. Finally, we obtained a three-armed star polyethylene oxide with azide terminal group(star PEO-3N3) trough a simple reaction with sodium azide, this product could be as the core of dendrimer-like polymer.2. Synthesis of the three generation dendrimer-like polyethylene oxide (G3-PEO-24Br) via arm-first First generation dendrimer-like polyethylene oxide(G1-PEO-6Br) was synthesized via click reaction between linear PEO and three-armed PEO in the presence of copper sulfate pentahydrate/sodium ascorbate. Then the first generation with azide terminal groups(G 1-PEO-6N3) easily prepared trough a azide reaction with sodium azide. Following the same procedures, we obtained the three generation polyethylene oxide with 24 bromine groups(G3-PEO-24Br).3. Synthesis of dendrimer-like polyethylene oxide via core-first A three-armed star polyethylene oxide with numerous hydroxyl groups was synthesized based on the anionic ring-opening polymerization of ethylene oxide, followed by AROP of a mixture of glycidol and propylene oxide via core-first. Following the same procedure, second generation of PEO obtained. After polymerization of EO and alkynyl reaction with 2-propargyl bromide, three generation dendrimer-like PEO with different molecular and alkynyl terminal groups were synthesized.