Copper(II) cyclam complexes with N-propionic acid pendant arms

Four cyclam (1,4,8,11-tetraazacyclotetradecane) ligands with different number of N-substituted propionic acid groups lead to penta-coordinated copper(II) complexes adopting trans-I configuration (4+1 geometry), i.e. the complexes have d_x2−y2 ground state with significant rhombic distortion. From the structural data (X-ray, electron paramagnetic resonance, UV/vis, infrared), it appears that with increasing substitution of the secondary amines of the macrocyclic ring with propionic acid groups the distortion from square-pyramidal to trigonal-bipyramidal rises, and this is expected to lead to relatively low complex stabilities. This is confirmed by in vitro studies using superoxide dismutase (SOD) and human serum challenge experiments as well as by biodistribution data with the ⁶⁴Cu-labelled ligands. ⁶⁴Cu-labelled cyclam monopropionic and dipropionic acid show high in vitro and in vivo stability at which the latter provides a comparable biodistribution profile as ⁶⁴Cu-TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid).