Interfacial liquid phase-driven removal of copper ions for bioavailable hyperbranched polytriazoles

The existence of toxic Cu ions in the products synthesized by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry hinders biomedical applications of these products. Cu ions are difficult to remove because stable Cu(II)–triazole coordination complexes are formed in the CuAAC products. To address this problem, we demonstrate a novel interfacial liquid phase-driven method for the removal of Cu ions. We synthesized small molecules, linear polymers, and hyperbranched polymers by using CuAAC. To remove Cu ions in these products, Cu ions were precipitated using Na₂S in a solvent mixture that contains water, dimethylformamide, and dichloromethane (DCM). The products and the CuS precipitates were automatically dispersed in the DCM phase and aqueous phase, respectively, resulting in separation of the products and CuS. Compared to the conventional Cu removal methods, our new method is highly efficient, fast, and generally applicable to small molecules and polymers. More than 98% Cu in the CuAAC products can be removed by using our method. Moreover, we tested the biocompatibility of hyperbranched polymers synthesized using CuAAC and purified using our method. These polymers are compatible to cells, indicating our Cu removal method shows promise in purification of biomaterials synthesized using CuAAC.