H₄octapa: Highly Stable Complexation of Lanthanide(III) Ions and Copper(II)

The acyclic ligand octapa^4– (H₄octapa = 6,6′-((ethane-1,2-diylbis­((carboxymethyl)­azanediyl))­bis­(methylene))­dipicolinic acid) forms stable complexes with the Ln³⁺ ions in aqueous solution. The stability constants determined for the complexes with La³⁺, Gd³⁺, and Lu³⁺ using relaxometric methods are log <i>K</i>_LaL = 20.13(7), log <i>K</i>_GdL = 20.23(4), and log <i>K</i>_LuL = 20.49(5) (<i>I</i> = 0.15 M NaCl). High stability constants were also determined for the complexes formed with divalent metal ions such as Zn²⁺ and Cu²⁺ (log <i>K</i>_ZnL = 18.91(3) and log <i>K</i>_CuL = 22.08(2)). UV–visible and NMR spectroscopic studies and density functional theory (DFT) calculations point to hexadentate binding of the ligand to Zn²⁺ and Cu²⁺, the donor atoms of the acetate groups of the ligand remaining uncoordinated. The complexes formed with the Ln³⁺ ions are nine-coordinated thanks to the octadentate binding of the ligand and the presence of a coordinated water molecule. The stability constants of the complexes formed with the Ln³⁺ ions do not change significantly across the lanthanide series. A DFT investigation shows that this is the result of a subtle balance between the increased binding energies across the 4f period, which contribute to an increasing complex stability, and the parallel increase of the absolute values of the hydration free energies of the Ln³⁺ ions. In the case of the [Ln­(octapa)­(H₂O)]⁻ complexes the interaction between the amine nitrogen atoms of the ligand and the Ln³⁺ ions is weakened along the lanthanide series, and therefore the increased electrostatic interaction does not overcome the increasing hydration energies. A detailed kinetic study of the dissociation of the [Gd­(octapa)­(H₂O)]⁻ complex in the presence of Cu²⁺ shows that the metal-assisted pathway is the main responsible for complex dissociation at pH 7.4 and physiological [Cu²⁺] concentration (1 μM)