Rapid synthesis of cross-bridged cyclam chelators for copper(II) complex formation

Copper(II) complexes of 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (cross-bridged cyclam) derived chelators show high kinetic stability relative to less rigid non-bridged azamacrocyclic chelators and have applications as radiopharmaceuticals in PET imaging. Rapid synthesis of two novel bis-benzyl cross-bridged cyclam derivatives was achieved in 24 h compared to the typical synthesis times, between 14 and 30 days. The X-ray crystal structures are reported for the copper(II) complexes with 1,3-dibromobenzyl and tolyl derivatives revealing different ligand coordination environments. Both structures show tetradentate coordination of the tetraazamacrocycle with axial elongation along the N–Cu–N axis for the 1,3-dibromobenzyl derivative (Cu–N distances: axial av. 2.48(8) Å, equatorial av. 2.081(7) Å).