How to Handle Hard-to-Purify Polymers: Ammonium Sulfate Precipitation of rPEG as a Prototype for Amorphous and Flexible Polymers

This work introduces a simple and effective method for purifying both amorphous and semicrystalline, flexible hydrophilic polymers by using ammonium sulfate precipitation (ASP), a technique commonly used in protein purification. ASP exploits the salting-out effect at high ionic strength to precipitate water-soluble polymers, leaving other substances in solution. We successfully purified amorphous and semicrystalline copolymers of ethylene oxide (EO) and racemic glycidyl methyl ether (GME), known as randomized PEG (rPEG), using ASP. The workup was performed from organic reaction media, yielding isolation yields of up to 97% while efficiently removing the solvent, low molar mass impurities and salts resulting from the synthesis. High purity of the isolated polymers was confirmed by NMR spectroscopy, size-exclusion chromatography, mass spectrometry and atomic absorption spectrometry. Owing to its cost-effectiveness and rapid implementation, ASP represents a viable alternative to conventional purification methods such as dialysis and high-pressure liquid chromatography and has the potential to purify a wide range of hydrophilic polymers beyond rPEG, e.g., for biomedical applications.