Purifying Low-Volume Combinatorial Polymer Libraries with Gel Filtration Columns

Recent advances in oxygen-tolerant controlled/living radical polymer chemistry now enable efficient synthesis of diverse and combinatorial polymer libraries. While library synthesis has been dramatically simplified, equally efficient purification strategies for removal of small-molecule impurities are not yet established in high throughput settings. It is shown that gel filtration columns for chromatography frequently used in the protein science community are well suited for high throughput polymer purification. Using either single-use columns or gel filtration plates, the purification of 32 diverse polymers is demonstrated in a library with >95% removal of small molecule impurities and >85% polymer retention in a single purification step. Doing so replaces the typical procedure of polymer precipitation, which requires solvent optimization for each polymer in a complex library. Overall, this work raises awareness in the polymer science community that gel filtration is amenable to purification of large polymer libraries and can speed up the progress of combinatorial polymer chemistry.