Monopicolinate-dipicolyl Derivative of Triazacyclononane for Stable Complexation of Cu2+ and 64CU2+

The synthesis and characterization of Hno1pa2py, a new tacn-based ligand, is reported. The complexation process with Cu2+ was proved to be very fast even in acidic medium. Potentiometric titrations allowed us to establish that Hno1pa2py exhibits an overall low basicity as well as a high selectivity for Cu2+ over Zn2+ cations. The copper(II) complex was synthesized and characterized using UV-vis and EPR spectroscopies and density functional theory (DFT) calculations. The studies clearly showed that the [Cu(no1pa2py)](+) complex is present in solution as a mixture of two isomers in which the ligand is coordinated to the metal center using a N5O donor set with the metal center in a distorted octahedral geometry. The very high kinetic inertness of the [Cu(no1pa2py)](+) complex was demonstrated by using acid assisted dissociation assays as well as cyclic voltammetry. Preliminary investigations of Cu-64 complexation were performed to validate the potential use of such chelating agent for further application in nuclear medicine. The X-ray crystal structures of copper(H) complexes of L1, the ester derivative of Hno1pa2py, have been determined.