H₂ampa─Versatile Chelator for [²⁰³Pb]Pb²⁺, [²¹³Bi]Bi³⁺, and [²²⁵Ac]Ac³

A new decadentate chelator, H₂ampa, 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, H₂ampa was paired with [^nat/203Pb]Pb²⁺, [^nat/213Bi]Bi³⁺, and ^natLa³⁺/[²²⁵Ac]Ac³⁺ 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)](NO₃) 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 H₂ampa coordinated Bi³⁺, Pb²⁺, and La³⁺ ions to obtain pM values of 26, 14.8, and 15.1, respectively. Preliminary concentration-dependent radiolabeling experiments were carried out between H₂ampa and three different radiometals to evaluate their compatibility for radiopharmaceutical applications. The chelator radiolabeled [²⁰³Pb]Pb²⁺, [²¹³Bi]Bi³⁺, and [²²⁵Ac]Ac³⁺ in short reaction times (7-30 min), at dilute concentrations, and under mild conditions. Thus, H₂ampa was proven to be a versatile chelator able to well coordinate a small range of radiometals frequently considered to be alpha therapeutic candidates.