Macrocyclic Pyclen-Based Gd³⁺ Complex with High Relaxivity and pH Response

We report the synthesis and characterization of the macrocyclic ligand 2,2'-((2-(3,9-bis(carboxymethyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)azanediyl)diacetic acid (H₄L) and several of its complexes with lanthanide ions. The structure of the free ligand was determined using X-ray diffraction measurements. Two N atoms of the pyclen moiety in the trans position are protonated in the solid state, together with the exocyclic N atom and one of the carboxylate groups of the ligand. The relaxivity of the Gd³⁺ complex was found to increase from 6.7 mM^-1 s^-1 at pH 8.6 to 8.5 mM^-1 s^-1 below pH ≈ 6.0. Luminescence lifetime measurements recorded from H₂O and D₂O solutions of the Eu³⁺ complex evidence the presence of a single complex species in solution at low pH (∼5.0) that contains two inner-sphere water molecules. DFT calculations suggest that the coordination environment of the Ln³⁺ ion is fulfilled by the four N atoms of the pyclen unit, two oxygen atoms of the macrocyclic acetate groups, and an oxygen atom of an exocyclic carboxylate group. The two inner-sphere water molecules complete coordination number nine around the metal ion. At high pH (∼9.3), the lifetime of the excited ⁵D₀ level of Eu³⁺ displays a biexponential behavior that can be attributed to the presence of two species in solution with hydration numbers of q = 0 and q = 1. The ¹H NMR and DOSY spectra recorded from solutions of the Eu³⁺ and Y³⁺ complexes reveal a structural change triggered by pH and the formation of small aggregates at high pH values.