Stable Mn2+, Cu2+ and Ln3+ complexes with cyclen-based ligands functionalized with picolinate pendant arms

[Abstract] In this study we present the results of the equilibrium, dissociation kinetics, DFT and X - ray crystallographic studies performed on the complexes of metal ions of biomedical importance (Mn 2+ , Cu 2+ and Gd 3+ ) formed with octadentate ligands based on a cyclen platform incorporating two picolinate pendant arms (dodpa 2− and Medodpa 2− ). The stability constants of the complexes were accessed by m ultiple methods (pH - potentiometry, direct and competition UV - vis spectrophotometry and 1 H - relaxometry). The stability constants of the complexes formed with dodpa 2− and Medodpa 2− do not differ significantly ( e.g. log K [Mn(dodpa)] = 17.40 vs. log K[Mn(Medodp a)] = 17.46, log K [Cu(dodpa)] = 24.34 – 25.17 vs. log K [Cu(Medodpa)] = 24.74 and log K [Gd(dodpa)] + = 17.27 vs . log K [Gd(Medodpa)] + = 17.59), which indicates that the steric hindrance brou ght by the methyl groups has no significant effect on the stability of the complexes. The stability constants of the Mn 2+ complexes formed with the cyclen dipicolinates were found to be ca. 3 log K units higher than t hose determined for the complex of the cyclen monopicolinate (dompa − ), which indicates that the se cond picolin ate moiety attached to the backbone of the macrocycle is very likely coordinated to the Mn 2+ ion . However, the stability of the [Cu(dodpa)] and [Cu(Medodpa)] complexes agrees well with the stability constant of [Cu(dompa)] + , in line with the hexadentate coordination around the metal ion observed in the X - ray structure of [Cu(Medodpa)]. The [Gd(dodpa)] + and [Gd(Medodpa)] + complexes display a fairly high kinetic inertness, as the rate constants of acid catalysed dissociation ( k 1 = 2.5(4) × 10 −3 and 8.3(4) × 10 −4 M −1 s −1 for [Gd(dodpa)] + and [Gd(Medodpa)] + , respectively) are smaller than the value reported for [Gd(do3a)] ( k 1 = 2.5 × 10 −2 M −1 s −1 ). The [Mn(dodpa)] complex was found to be more inert than [Mn(Medodpa) ]. The results of the diffusion ordered NMR