Heavy metal on stage: Making ion-exchange resin selective by peptide tetrazine-norbornene ligation

The challenge of recycling metal salt-contaminated wastewater is more relevant than ever, and cost-effective materials for specific ion-binding are required. A generic route to functionalize a macroporous polystyrene ion-exchange resin (LR-NH2) via chemoselective inverse electron-demand Diels-Alder (IEDDA) ligation is demonstrated. The resin is modified using accessible endo-/exo-5-norbornene-2-carboxylic acid (Nb-COOH) and a set of tetrazine-functionalized 5mer peptides based on sequence variations of the literature known Cu2+ binding domain HGGGW is employed for the IEDDA ligation. The resulting peptide-functionalized resins (LR-Pz-Peptides) are studied for Cu2+ binding to correlate ion-binding capacity with sequence properties by single bead analysis of metal amounts via inductively-coupled plasma mass spectrometry (ICP-MS). The complexation preferences are demonstrated and utilized for specific binding of Cu2+ versus Ni2+ from 1:1 salt mixture as a model system. Enrichment factors of up to 305 could be realized, which might open the potential for applications in metal recycling or waste water purification.