Comparative Study of Macrocyclic and Acyclic Picolinate Derivatives for Chelation of Copper Cations

In this work we presented a synthesis and investigation of relative acyclic and macrocyclic polyamines with picolinate pendant arms as potential chelators for copper radiopharmaceuticals. It has been shown that linear chelators lacking bisamide moiety are much more basic and form complexes with higher stability constants compared to macrocyclic ones. Both types of ligands possess many donor sites due to picolinate groups enabling formation of polynuclear complexes in the solution and solid state. According to crystal structures metal cations coordinates with studied ligands through the binding with aminogroups and picolinates donor atoms, while terminal aminogroups of acyclic ligands do not take part in the complex formation. Tripicolinate azacrown ligand coordinates cations outside the macrocyclic cavity in non‐equivalent positions. However this out‐cage location as well as a moderate logK value do not induce fast release of cation from this complex in the challenging medium of serum proteins.