Development of a Highly Selective Ni(II) Chelator in Aqueous Solution

The design, synthesis, and characterization of a novel Ni(II) chelator SG-20 is reported. SG-20 is selective in binding to Ni(II) versus other metal ions including Cu(II), Fe(II), Co(II), and Zn(II). At pH = 7.1, SG-20 binds Ni(II) with a Kd = 7.0 ± 0.4 μM. Job analysis indicates that SG-20 binds to both Ni(II) and Cu(II) with a 1:1 stoichiometry. Affinity of SG-20 for Ni(II) is pH dependent and decreases upon lowering to pH 4.0. A green solid was isolated from the reaction of SG-20 with NiCl2·6H2O in MeOH and characterized by X-ray photoelectron spectroscopy (XPS), electronic absorption and infrared (IR) spectroscopies, and mass spectrometry. Collectively, XPS and IR analysis revealed Ni-N and Ni-O interactions and a shift in C-O asymmetric and symmetric stretches consistent with Ni binding. Attempts to crystalize a mononuclear complex were unsuccessful, likely due to the Ni-SG-20 complex being in equilibrium with higher order species in solution. However, reaction of SG-20 with NiCl2·6H2O in water followed by slow evaporation yielded green crystals that were characterized by electronic absorption spectroscopy (λmax = 260 nm) and X-ray crystallography. These analyses revealed that SG-20 supports formation of a complex cluster containing six SG-20 ligands, 15 Ni(II), and three Na(I) centers, with two distinct types of Ni atoms in its outer and inner core. The nine Ni atoms present in the inner core were bound by oxo and carbonate bridges, whereas the six Ni atoms present in its outer shell were bound to N, O, and S donor atoms derived from SG-20. Overall, X-ray crystallographic analysis revealed that two chelator arms of SG-20 bind to one Ni(II) ion with an axial aqua ligand, whereas the third arm is free to interact with Ni ions within the central cluster, supporting the goal of Ni capture.