Facile Access to the 12‐Membered Macrocyclic Ligand PCTA and Its Derivatives with Carboxylate, Amide, and Phosphinate Ligating Functionalities

We describe a convenient synthetic pathway to access the 12-membered PCTA macrocycle, a polyaminocarboxylate ligand for which its M2+ and M3+ complexes are commonly associated with applications in biomedical diagnostics and radiotherapy. The synthetic pathway is based on the use of a linear tri-N-alkylated triamine synthon incorporating masked acetate arms and an efficient sodium template ion effect for the crucial macrocyclization step (87% macrocyclization yield). This approach was then successfully applied to access three new PCTA[12] derivatives containing either a 4-pyridol unit, an amide or a phosphinate coordinating function in the central arm. In all cases, the macrocyclization reactions were controlled by a sodium template ion effect, and the macrocyclization yields were in the range of 60 to 75%. The luminescence and relaxometric properties of Eu-III, Tb-III, and Gd-III complexes derived from PCTA derivatives with mixed coordinating arms were also investigated, making these complexes possible alternatives to PCTA[12]-Ln(III) complexes.