Selective removal of copper from complex biological media with an agarose-immobilized high-affinity PSP ligand.

The elucidation of metal-dependent biological processes requires selective reagents for manipulating metal ion levels within biological solutions such as growth media or cell lysates. To this end, we immobilized a phosphine sulfide-stabilized phosphine (PSP) ligand on agarose to create a resin for the selective removal of copper from chemically complex biological media through simple filtration or centrifugation. Comprised of a conformationally preorganized phenylene-bridged backbone, the PSP-ligand binds Cu(I) with a 1:1 stoichiometry and exhibits a pH-independent Cu(I) dissociation constant in the low zeptomolar range.

Stabilization of Aliphatic Phosphines by Auxiliary Phosphine Sulfides Offers Zeptomolar Affinity and Unprecedented Selectivity for Probing Biological Cu.

Full elucidation of the functions and homeostatic pathways of biological copper requires tools that can selectively recognize and manipulate this trace nutrient within living cells and tissues, where it exists primarily as Cu . Buffered at attomolar concentrations, intracellular Cu is, however, not readily accessible to commonly employed amine and thioether-based chelators. Herein, we reveal a chelator design strategy in which phosphine sulfides aid in Cu coordination while simultaneously stabilizing aliphatic phosphine donors, producing a charge-neutral ligand with low-zeptomolar dissociation constant and 10 -fold selectivity for Cu over Zn , Fe , and Mn .