H 2 ampa─Versatile Chelator for [ 203 Pb]Pb 2+ , [ 213 Bi]Bi 3+ , and [ 225 Ac]Ac 3 .

A new decadentate chelator, H 2 ampa, was designed to be a potential radiopharmaceutical chelator component. The chelator involves both amide and picolinate functional groups on a large non-macrocyclic, ether-bridged backbone. With its large scaffold, H 2 ampa was paired with [ nat/203 Pb]Pb 2+ , [ nat/213 Bi]Bi 3+ , and nat La 3+ /[ 225 Ac]Ac 3+ ions. Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to study the non-radioactive metal complexes. A single crystal of [Bi(ampa)](NO 3 ) was obtained; its asymmetric, 10-coordinate complex structure was revealed by X-ray diffraction. Optimal conformations of the metal complexes were assessed by density functional theory studies to provide further structural information. Solution studies providing thermodynamic insights into metal complex formation revealed H 2 ampa coordinated Bi 3+ , Pb 2+ , and La 3+ ions to obtain pM values of 26, 14.8, and 15.1, respectively. Preliminary concentration-dependent radiolabeling experiments were carried out between H 2 ampa and three different radiometals to evaluate their compatibility for radiopharmaceutical applications. The chelator radiolabeled [ 203 Pb]Pb 2+ , [ 213 Bi]Bi 3+ , and [ 225 Ac]Ac 3+ in short reaction times (7-30 min), at dilute concentrations, and under mild conditions. Thus, H 2 ampa was proven to be a versatile chelator able to well coordinate a small range of radiometals frequently considered to be alpha therapeutic candidates.